bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelets and platelet-derived serotonin promote tissue repair after normothermic hepatic ischemia in mice
Authors: Nocito Antonio , Georgiev Panco , Dahm Felix , Jochum Wolfram , Bader Michael , Graf Rolf , Clavien Pierre-Alain
Published: January 2007

Hepatic ischemia and reperfusion (I/R) leads to the formation of leukocyte–platelet aggregates. Upon activation, platelets generate reactive oxygen species and release proapoptotic and proinflammatory mediators as well as growth factors. In cold hepatic ischemia, adhesion of platelets to endothelial cells mediates sinusoidal endothelial cell apoptosis. Furthermore, platelet-derived serotonin mediates liver regeneration. We hypothesized that platelets may contribute to reperfusion injury and repair after normothermic hepatic ischemia. The aim of this study was to assess the impact of platelets in normothermic hepatic I/R injury using models of impaired platelet function and immune thrombocytopenia. Inhibition of platelet function in mice was achieved via clopidogrel feeding. Immune thrombocytopenia was induced via intraperitoneal injection of anti-CD41 antibody. Platelet-derived serotonin was investigated using mice lacking tryptophan hydroxylase 1. Mice were subjected to 60 minutes of partial hepatic ischemia and various time points of reperfusion. Hepatic injury was determined via AST and histological analysis of the necrotic area as well as leukocyte infiltration. Liver regeneration was determined via proliferating cell nuclear antigen and Ki67 immunohistochemistry. Neither inhibition of platelet function nor platelet depletion led to a reduction of I/R injury. Liver regeneration and repair were significantly impaired in platelet-depleted animals. Mice lacking peripheral serotonin were deficient in hepatocyte proliferation, but otherwise displayed normal tissue remodeling.

Conclusion:

Platelets have no direct impact on the pathogenesis of normothermic I/R injury. However, they mediate tissue repair and liver regeneration. Furthermore, platelet-derived serotonin is a mediator of hepatocyte proliferation in the postischemic liver, but has no impact on tissue remodeling.
A national French survey on the use of growth factors as adjuvant treatment of chronic hepatitis C
Authors: Thévenot Thierry , Cadranel Jean-François , Di Martino Vincent , Pariente Alexandre , Causse Xavier , Renou Christophe , Hagege Hervé , Denis Jacques , Lunel-Fabiani Françoise
Published: January 2007

We conducted a national retrospective survey on hospital practitioners to evaluate the magnitude of erythropoietin (EPO) or granulocyte colony-stimulating factor (G-CSF) prescriptions in patients treated for chronic hepatitis C. Four hundred seventy-one questionnaires were sent, and 274 practitioners (58.2%) responded. Forty-six percent of practitioners used EPO, and 31% used G-CSF. The total number of HCV-infected patients receiving antiviral therapy per year was estimated at 6,630 patients, of whom 8.8% and 4% received EPO and G-CSF, respectively. EPO-β was the main EPO molecule prescribed at a median dose of 30,000 IU/wk (range: 2,000-80,000). The indications for prescribing EPO varied greatly, including “fragile patients” (34%), “low” Hb level (8-11 g/dL) (19%), “rapid decline” in Hb level (2-5 g/dL during the first month of therapy) (12%), and symptomatic anemic patients (7%). G-CSF was mainly prescribed for a “low” level of neutrophils ranging from 400 to 750 neutrophils/mm3. In multivariate analysis, independent predictors of EPO and G-CSF prescription were age of practitioner less than 45 years (EPO: OR = 1.96,

P

= 0.03; G-CSF: OR = 2.27,

P

= 0.004), practice in university hospital (EPO: OR = 5.89,

P

< 0.0001; G-CSF: OR = 2.39,

P

= 0.003), and the high number of CHC treated/year (EPO: OR = 6.18,

P

< 0.0001; G-CSF: OR = 2.58,

P

= 0.002).

Conclusion :

Our survey reveals an important rate of EPO and G-CSF prescriptions but with considerable disparity in the schedule of injections, the molecules used, and above all the indications. The suitable role of EPO and G-CSF as complements to HCV therapy urgently needs to be clarified.
A genomewide DNA microsatellite association study of Japanese patients with autoimmune hepatitis type 1
Authors: Yokosawa Shuichi , Yoshizawa Kaname , Ota Masao , Katsuyama Yoshihiko , Kawa Shigeyuki , Ichijo Tetsuya , Umemura Takeji , Tanaka Eiji , Kiyosawa Kendo
Published: January 2007

Genetic predisposition to type 1 autoimmune hepatitis (AIH) is linked mainly to HLA class II genes. We previously searched the whole HLA region for AIH susceptibility genes using microsatellite markers and found only HLA-DR/DQ to be a candidate region for this suspected multifactorial disease. As such, the aim of this study was to broaden our search and screen the whole genome for additional genes that might contribute to type 1 AIH susceptibility. Eighty-one patients with type 1 AIH (15 men, 66 women, average age 55.9) and 80 healthy sex- and age-matched Japanese controls were enrolled in this study. We performed a case-control association study using 400 polymorphic microsatellite markers with an average spacing of 10.8 cM distributed throughout the whole genome. Two markers, one on chromosome 11 (D11S902, Pc = 0.013) and one on chromosome 18 (D18S464, Pc = 0.008), were revealed to have statistically significant associations with AIH. An additional 7 markers (D2S367, D6S309, D9S273, D11S1320, D16S423, D17S938, and D18S68) were also found to be candidate susceptibility regions. In addition, our results showed there were 17 regions that may contain genes of resistance to AIH. No specific markers were detected in HLA-DR4-negative patients, and no differences were seen in the clinical courses of patients (severe versus mild to moderate).

Conclusion :

This first genomewide scan of Japanese AIH patients revealed at least 26 candidate AIH susceptibility or resistance regions other than HLA class II loci. These results also suggested that the products of several genes interact to determine heritable susceptibility to AIH.
Mutual changes of thioredoxin and nitrosothiols during biliary cirrhosis: Results from humans and cholestatic rats
Authors: Grattagliano Ignazio , Portincasa Piero , Palmieri Vincenzo O. , Palasciano Giuseppe
Published: January 2007

Cholestasis is associated with changes in NO metabolism and thiol oxidation. Thioredoxin contributes to regulate vascular tone and intracellular redox status by cleaving nitrosothiols and maintaining −SH groups. This study investigated the changes in circulating thioredoxin and nitrosothiols and the relationship with protein sulfhydryls (PSH), hepatic concentrations, hyaluronate, and histology in patients with primary biliary cirrhosis (PBC) and in rats with bile duct ligation (BDL). PSH in erythrocytes were significantly decreased in stage III and IV PBC and at day 10 after BDL. Compared with controls, erythrocyte thioredoxin levels were higher in stage I through III PBC and lower in stage IV patients. Serum thioredoxin levels were significantly higher in PBC stages I and II and lower in stages III and IV. Serum nitrosothiols were higher in all PBC patients and inversely related to thioredoxin and hyaluronate. In rats, serum, hepatic, and mitochondrial thioredoxin had initially increased after BDL (day 1-3) and then decreased. After day 7 BDL, nitrosothiols were 10-fold increased in serum and liver, and even higher in mitochondria. In the liver, thioredoxin was inversely related to both nitrosothiols and PSH. In rats, the difference in time average changes from baseline among serum, hepatic, and erythrocyte thioredoxin suggests that most of circulating thioredoxin originates from the liver.

Conclusion:

Our findings indicate that cholestasis is associated with significant mutual and interrelated changes between circulating and hepatic thioredoxin and nitrosothiols. The increase of hepatic, mitochondrial, and circulating nitrosothiols with ongoing cholestasis suggests an active participation of NO in both liver injury and extrahepatic changes.
Fibroindex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C
Authors: Koda Masahiko , Matunaga Yoshiko , Kawakami Manri , Kishimoto Yukihiro , Suou Takeaki , Murawaki Yoshikazu
Published: January 2007

Diagnosis of the stage of liver fibrosis in chronic hepatitis C is essential for making a prognosis and deciding on antiviral therapy. In the present study a simple model consisting of routine laboratory tests was constructed and then validated in cross-sectional and longitudinal investigations. Consecutive treatment-naive patients with chronic hepatitis C who had undergone liver biopsy were divided into 2 cohorts: an estimation set (n = 240) and a validation set (n = 120). A longitudinal set consisted of 30 patients who had undergone a liver biopsy twice, before and after IFN treatment. The FibroIndex was derived from the platelet count, AST, and gamma globulin measurements in the estimation set. The areas under the ROC curves of the FibroIndex for predicting significant fibrosis were 0.83 and 0.82 for the validation set, better than those of the Forns index and the aminotransferase-to-platelet ratio index (APRI). Using the best cutoff values, whether significant fibrosis was present was diagnosed with high positive predictive values, and 35% of patients could avoid liver biopsy. In the longitudinal set, there was a significant decrease in the FibroIndex of 14 patients whose fibrosis stage improved, and a significant increase in that of 5 patients whose fibrosis stage deteriorated. Change in the FibroIndex correlated significantly with variation in fibrosis stage. There was no such correlation with the Forns index or the APRI.

Conclusion:

The FibroIndex is a simple and reliable index for predicting significant fibrosis in chronic hepatitis C and could also be used as a surrogate marker during antifibrotic treatment for chronic hepatitis C.
AMA production in primary biliary cirrhosis is promoted by the TLR9 ligand CpG and suppressed by potassium channel blockers
Authors: Moritoki Yuki , Lian Zhe-Xiong , Wulff Heike , Yang Guo-Xiang , Chuang Ya-Hui , Lan Ruth Y. , Ueno Yoshiyuki , Ansari Aftab A. , Coppel Ross L. , Mackay Ian R. , Gershwin Eric M.
Published: January 2007

We previously reported that peripheral blood mononuclear cells (PBMCs) from patients with primary biliary cirrhosis (PBC) produce significantly higher levels of polyclonal IgM than controls after exposure to CpG. Furthermore, the prevalence and unusually high levels of antimitochondrial antibodies (AMAs) in patients with PBC suggest a profound loss of B cell tolerance. We have addressed the issue of whether CpG will promote the production of AMAs and whether new experimental agents that inhibit the lymphocyte potassium channels Kv1.3 and KCa3.1 can suppress CpG-mediated B cell activation and AMA production. PBMCs were stimulated with and without CpG and were subsequently analyzed for phenotype, including expression of TLR9, CD86, and KCa3.1 concurrent with measurements of AMA and responses to a control antigen, tetanus toxoid, in supernatants. Additionally, K+ channel expression on B cells from PBC patients and controls was studied using whole-cell patch-clamp technology. In patients with PBC, CpG induces secretion of AMAs in PBMCs and also up-regulates B cell expression of TLR9, CD86, and KCa3.1. Additionally, K+ channel blockers suppress secretion of AMA without a reduction of CpG-B–enhanced IgM production. Furthermore, there is diminished up-regulation of TLR9 and CD86 without affecting proliferation of B cells, B cell apoptosis, or viability.

Conclusion:

These data suggest that the hyperresponsiveness of B cells in PBC accelerates B cell–mediated autoimmunity.
Liver-specific loss of β-catenin results in delayed hepatocyte proliferation after partial hepatectomy
Authors: Sekine Shigeki , Gutiérrez Pedro J. A. , Yu-Ang Lan Billy , Feng Sandy , Hebrok Matthias
Published: January 2007

Recent studies have suggested that β-catenin is involved in the regulation of hepatocyte proliferation in multiple contexts, including organ development and tumorigenesis. We explored the role of β-catenin during liver regeneration using T cell factor/lymphoid enhancer factor (TCF/LEF)-reporter mice (TOPGal mice) and liver-specific β-catenin knockout mice. Liver-specific β-catenin knockout mice showed a delayed onset of DNA synthesis after hepatectomy, whereas recovery of liver mass was not affected. Among putative β-catenin target genes examined, the induction of

Ccnd1

expression was reduced, whereas the expression of

Myc

and

Egfr

was unaffected. Furthermore, cyclin D1 protein levels were not induced, and the expression of cyclins A, E, and proliferating cell nuclear antigen was delayed. Intriguingly, the analysis of TOPGal mice showed that hepatocytes with active TCF/LEF transcription are confined to the pericentral zone and are not increased in number during regeneration, indicating an uncoupling between β-catenin/TCF signaling activity and hepatocyte proliferation.

Conclusion:

Our results indicate that β-catenin is critical for the proper regulation of hepatocyte proliferation during liver regeneration; however, the activity of β-catenin/TCF signaling does not correlate with hepatocyte proliferation, suggesting that this regulation might be indirect/secondary.
Human and rat bile acid–CoA:amino acid N -acyltransferase are liver-specific peroxisomal enzymes: Implications for intracellular bile salt transport
Authors: Pellicoro Antonella , van den Heuvel Fiona A. J. , Geuken Mariska , Moshage Han , Jansen Peter L. M. , Faber Klaas Nico
Published: January 2007

Bile acid–coenzyme A:amino acid

N

-acyltransferase (BAAT) is the sole enzyme responsible for conjugation of primary and secondary bile acids to taurine and glycine. Previous studies indicate a peroxisomal location of BAAT in peroxisomes with variable amounts up to 95% detected in cytosolic fractions. The absence or presence of a cytosolic pool of BAAT has important implications for the intracellular transport of unconjugated/deconjugated bile salts. We used immunofluorescence microscopy and digitonin permeabilization assays to determine the subcellular location of endogenous BAAT in primary human and rat hepatocytes. In addition, green fluorescent protein (GFP)–tagged rat Baat (rBaat) and human BAAT (hBAAT) were transiently expressed in primary rat hepatocytes and human fibroblasts. Catalase and recombinant GFP-SKL and DsRed-SKL were used as peroxisomal markers. Endogenous hBAAT and rBaat were found to specifically localize to peroxisomes in human and rat hepatocytes, respectively. No significant cytosolic fraction was detected for either protein. GFP-tagged hBAAT and rBaat were efficiently sorted to peroxisomes of primary rat hepatocytes. Significant amounts of GFP-tagged hBAAT or rBaat were detected in the cytosol only when coexpressed with DsRed-SKL, suggesting that hBAAT/rBaat and DsRed-SKL compete for the same peroxisomal import machinery. When expressed in fibroblasts, GFP-tagged hBAAT localized to the cytosol, confirming earlier observations.

Conclusion:

hBAAT and rBaat are peroxisomal enzymes present in undetectable amounts in the cytosol. Unconjugated or deconjugated bile salts returning to the liver need to shuttle through the peroxisome before reentering the enterohepatic circulation.
Iridoid Glycosides from Lamiophlomis rotata
Authors: Tan Jun‐Jie , Tan Chang‐Heng , Li Mu , Jiang Shan‐Hao , Zhu Da‐Yuan
Published: January 2007

The seven new iridoid diglycosides 1–7, together with eleven known iridoid and phenylpropanoid glycosides, were isolated from the 50% EtOH extract of the roots of Lamiophlomis rotata. Their structures were elucidated by chemical and spectroscopic methods.
Lycopodium Alkaloids from Huperzia serrata
Authors: Wang Heng‐Bin , Tan Chang‐Heng , Tan Jun‐Jie , Gao Ming‐Yao , Li Yi‐Ming , Jiang Shan‐Hao , Zhu Da‐Yuan
Published: January 2007

Three new Lycopodium alkaloids, 2‐chlorohuperzine E (1), huperzines E′ (2), and F′ (3), along with two known compounds, huperzines E and F, were isolated from Huperzia serrata (Thunb.) Trev. Their structures were elucidated by spectroscopic methods.
Chemical Constituents of Ligusticum sinensisOliv.
Authors: Ma Jian‐Ping , Tan Chang‐Heng , Zhu Da‐Yuan
Published: January 2007

The new phenylpropanoid diglycoside ligusinenoside A (1), and the two new 8,4′‐oxyneolignan(‘8‐O‐4′‐neolignan’) diglycosides ligusinenosides B (2) and C (3), together with nine known compounds, were isolated from the rhizomes of Ligusticum sinensis Oliv. The structures of 1–3 were elucidated on the basis of spectroscopic analyses.
Sesquiterpene Lactones from Anthemis melanolepis
Authors: Saroglou Vasiliki , Karioti Anastasia , Heilmann Jörg , Kypriotakis Zacharias , Skaltsa Helen
Published: January 2007

From the aerial parts of A. melanolepis, two new sesquiterpene lactones, melanolepin B ( = 1α,4β,8α‐trihydroxyeudesm‐11(13)‐en‐12,6α‐olide; 1) and melanolepin C (= 1α,10β‐epoxy‐8β‐hydroxygermacra‐4(15),11(13)‐dien‐12,6α‐olide; 2), were isolated, together with four known compounds, desacetyllaurenobiolide, dentatin A, taraxasterol, and (3S,5R)‐loliolide. Compound 1 was found to have the rare cis‐fused eudesmane skeleton. The structures of the isolated compounds were established by means of NMR (1H, 1H‐COSY, 1H,13C‐HSQC, HMBC, NOESY) and MS analyses.
Benzofuran Derivatives from Gerbera saxatilis
Authors: Chen Yan‐Jun , Li Ya , Chen Jian‐Jun , Gao Kun
Published: January 2007

Three new substituted 2,3‐dihydro‐1‐benzofuran derivatives, compounds 1–3, were isolated from two extracts of Gerbera saxatilis, together with twelve known constituents. The structures of the new compounds were established by means of detailed spectroscopic analysis and by comparison of analytical data with those reported for structurally related compounds.
Total Synthesis of (2Z)‐[(4R,5R,6S)‐6‐(β‐D‐Glucopyranosyloxy)‐4,5‐dihydroxycyclohex‐2‐en‐1‐ylidene]ethanenitrile, a Cyanoglucoside from Ilex warburgii
Authors: Josien‐Lefebvre Delphine , Le Drian Claude
Published: January 2007

The total synthesis of the noncyanogenic cyanoglucoside 1, originally isolated from Ilex warburgii, was achieved in nine steps (9% overall yield), starting from an optically pure Diels–Alder adduct ((+)‐3). The key step of the synthesis, the glycosidation, was carried out under Koenigs–Knorr conditions closely related to those developed for the total syntheses of (−)‐lithospermoside and (−)‐bauhinin. We had to tune the protecting groups used for the two free cis‐configured OH groups of the aglycone, which afforded the desired β‐d‐glucoside intermediate 15 in very good yield (62%).
Secoleuconoxine and Oxopericine Derivatives from Kopsia
Authors: Lim Kuan‐Hon , Kam Toh‐Seok
Published: January 2007

Two new indole alkaloids, viz., arboloscine (1), the first example of a secoleuconoxine, and pericidine (5), an oxidized derivative of pericine (6), were obtained as minor alkaloids from the stem‐bark extract of the Malayan Kopsia species, K. arborea. Their structures were established by spectroscopic analysis.
Rearranged Calamenene and Eudesmane Sesquiterpenoids from two Chinese Liverworts
Authors: Ma Bin , Lu Zhi‐Qiang , Guo Huai‐Fang , Lou Hong‐Xiang
Published: January 2007

Four novel rearranged calamenene sesquiterpenoids, 1–4, and two eudesmane sesquiterpenoids, 5 and 6, were isolated from the Chinese liverworts Chiloscyphus polyanthus (L.) and Bazzania japonica S. (Lac.) Lindb. Their structures and relative configurations were determined by chemical derivatization and in‐depth spectroscopic methods, especially 1D‐ and 2D‐NMR as well as HR‐MS analyses.
A New Lignan and two Eudesmanes from Lepidozia vitrea
Authors: Ma Bin , Guo Huai‐Fang , Lou Hong‐Xiang
Published: January 2007

A new lignan, 1, was isolated from Lepidozia vitrea, together with two known eudesmane terpenoids, 2 and 3, as well as 7,8‐dihydroxycoumarin (4). Their structures were elucidated on the basis of extensive 1D‐ and 2D‐NMR as well as MS analyses.
Five New Steroidal Glycosides from Caralluma dalzielii
Authors: Oyama Masayoshi , Iliya Ibrahim , Tanaka Toshiyuki , Iinuma Munekazu
Published: January 2007

Five new pregnane glycosides, caradalzielosides A–E (1–5), were isolated from the aerial parts of Caralluma dalzielii. Their structures were elucidated by extensive 1D‐ and 2D‐NMR spectroscopic analysis as well as by HR‐FAB‐MS experiments.
Reactions of Methyl Diazoacetate with (E)‐ and (Z)‐1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile: Novel and Unanticipated Pathways
Authors: Huisgen Rolf , Mlostoń Grzegorz , Pöchlauer Peter , Fišera Lubor , Giera Henry
Published: January 2007

The cycloadditions of methyl diazoacetate to 2,3‐bis(trifluoromethyl)fumaronitrile ((E)‐BTE) and 2,3‐bis(trifluoromethyl)maleonitrile ((Z)‐BTE) furnish the 4,5‐dihydro‐1H‐pyrazoles 13. The retention of dipolarophile configuration proceeds for (E)‐BTE with > 99.93% and for (Z)‐BTE with > 99.8% (CDCl3, 25°), suggesting concertedness. Base catalysis (1,4‐diazabicyclo[2.2.2]octane (DABCO), proton sponge) converts the cycloadducts, trans‐13 and cis‐13, to a 94 : 6 equilibrium mixture (CDCl3, r.t.); the first step is N‐deprotonation, since reaction with methyl fluorosulfonate affords the 4,5‐dihydro‐1‐methyl‐1H‐pyrazoles. Competing with the cis/trans isomerization of 13 is the formation of a bis(dehydrofluoro) dimer (two diastereoisomers), the structure of which was elucidated by IR, 19F‐NMR, and 13C‐NMR spectroscopy. The reaction slows when DABCO is bound by HF, but F− as base keeps the conversion to 22 going and binds HF. The diazo group in 22 suggests a common intermediate for cis/trans isomerization of 13 and conversion to 22: reversible ring opening of N‐deprotonated 13 provides 18, a derivative of methyl diazoacetate with a carbanionic substituent. Mechanistic comparison with the reaction of diazomethane and dimethyl 2,3‐dicyanofumarate, a related tetra‐acceptor‐ethylene, brings to light unanticipated divergencies.
Muscle MRI in inherited neuromuscular disorders: Past, present, and future
Authors: Mercuri Eugenio , Pichiecchio Anna , Allsop Joanna , Messina Sonia , Pane Marika , Muntoni Francesco
Published: January 2007

Interest in muscle MRI has been largely stimulated in the last few years by the recognition of an increasing number of genetic defects in the field of inherited neuromuscular disorders. Muscle ultrasound (US) and computed tomography (CT) have been used to detect the presence of muscle involvement in patients affected by these disorders, but until recently the use of muscle MRI has been, with a few exceptions, limited to detecting inflammatory forms. The aim of this review is to illustrate how muscle MRI, in combination with clinical evaluation, can contribute to the selection of appropriate genetic tests and more generally in the differential diagnosis of genetically distinct forms of neuromuscular disorders. Possible future applications of muscle MRI are also discussed. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Structural and functional assessment of trabecular and cortical bone by micro magnetic resonance imaging
Authors: Wehrli Felix W.
Published: January 2007

Osteoporosis is a multifactorial disorder of bone mineral homeostasis affecting the elderly. It is a major public health issue with significant socioeconomic consequences. Recent findings suggest that bone loss—the key manifestation of the disease—is accompanied by architectural deterioration, both affecting the bone's mechanical competence and susceptibility to fracture. This article reviews the potential of quantitative micro MRI (μ‐MRI), including a discussion of the technical requirements for image acquisition, processing, and analysis for assessing the architectural implications of osteoporosis and as a means to monitor the response to treatment. With current technology, the resolution achievable in clinically acceptable scan times and necessary signal‐to‐noise ratio (SNR) is comparable to trabecular thickness. This limited spatial resolution regime demands processing and analysis algorithms designed to operate under such limiting conditions. It is shown that three different classes of structural parameters can be distinguished, characterizing scale, topology, and orientation. There is considerable evidence that osteoporotic bone loss affects all three classes but that topological changes, resulting from conversion of trabecular plates to rods, with the latter's eventual disconnection, are particularly prominent. Clinical applications discussed can be divided into those dealing with assessment of osteoporotic fracture risk as opposed to the study of the effect of disease progression and regression in response to treatment. Current data suggest that noninvasive assessment of cortical and trabecular bone (TB) architecture by μ‐MRI may provide new surrogate endpoints to assess the efficacy of intervention in osteoporosis treatment and prevention. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Collagen structure: The molecular source of the tendon magic angle effect
Authors: Fullerton Gary D. , Rahal Andrés
Published: January 2007

This review of tendon/collagen structure shows that the orientational variation in MRI signals from tendon, which is referred to as the “magic angle” (MA) effect, is caused by irreducible separation of charges on the main chain of the collagen molecule. These charges are held apart in a vacuum by stereotactic restriction of protein folding due in large part to a high concentration of hydroxyproline ring residues in the amino acids of mammalian collagen. The elevated protein electrostatic energy is reduced in water by the large dielectric constant of the highly polar solvent (κ ∼ 80). The water molecules serve as dielectric molecules that are bound by an energy that is nearly equivalent to the electrostatic energy between the neighboring positive and negative charge pairs in a vacuum. These highly immobilized water molecules and secondary molecules in the hydrogen‐bonded water network are confined to the transverse plane of the tendon. Orientational restriction causes residual dipole coupling, which is directly responsible for the frequency and phase shifts observed in orientational MRI (OMRI) described by the MA effect. Reference to a wide range of biophysical measurements shows that native hydration is a monolayer on collagen hm = 1.6 g/g, which divides into two components consisting of primary hydration on polar surfaces hpp = 0.8 g/g and secondary hydration hs = 0.8 g/g bridging over hydrophobic surface regions. Primary hydration further divides into side‐chain hydration hpsc = 0.54 g/g and main‐chain hydration hpmc = 0.263 g/g. The main‐chain fraction consists of water that bridges between charges on the main chain and is responsible for almost all of the enthalpy of melting ΔH = 70 J/g‐dry mass. Main‐chain water bridges consist of one extremely immobilized Ramachandran water bridge per tripeptide hRa = 0.0658 g/g and one double water bridge per tripeptide hdwb = 0.1974 g/g, with three water molecules that are sufficiently slowed to act as the spin‐lattice relaxation sink for the entire tendon. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Frontiers in musculoskeletal MRI: Articular cartilage
Authors: Kneeland J. Bruce , Reddy Ravinder
Published: January 2007

The techniques and uses of MRI in current clinical practice, primarily as a means to detect morphologic abnormalities, are reviewed. Ongoing development of techniques that can improve morphologic assessment including techniques to increase spatial and contrast resolution is discussed, as are methods to measure cartilage volumes and thickness. Finally, several of the more widely studied techniques used to probe loss of the macromolecular structure of cartilage prior to the development of macroscopic defects are presented and compared. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Ultra‐high‐field MRI of the musculoskeletal system at 7.0T
Authors: Regatte Ravinder R. , Schweitzer Mark E.
Published: January 2007

High‐field (3T) and ultra‐high‐field (UHF, 7T and above) systems are increasingly being used to explore potential musculoskeletal applications because they provide a high intrinsic signal‐to‐noise ratio (SNR), potentially higher resolution (spatial and temporal), and improved contrast. However, imaging at 7T and above presents certain challenges, such as homogeneous radiofrequency (RF) coil design, increased chemical shift artifacts, susceptibility artifacts, RF energy deposition, and changes in relaxation times compared to more typical clinical scanners (1.5 and 3T). Despite these issues, MRI at 7T likely will provide some excellent opportunities for high‐resolution morphologic imaging and forays into functional imaging of musculoskeletal systems. In this review we address some of these issues and also demonstrate the feasibility of acquiring high‐resolution in vivo images of the musculoskeletal system in healthy human volunteers at 7.0T. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Applications of magnetic resonance elastography to healthy and pathologic skeletal muscle
Authors: Ringleb Stacie I. , Bensamoun Sabine F. , Chen Qingshan , Manduca Armando , An Kai‐Nan , Ehman Richard L.
Published: January 2007

Magnetic resonance elastography (MRE) is capable of noninvasively quantifying the mechanical properties of skeletal muscles in vivo. This information can be clinically useful to understand the effects of pathologies on the mechanical properties of muscle and to quantify the effects of treatment. Advances in inversion algorithms quantify muscle anisotropy in two‐dimensional (2D) and three‐dimensional (3D) imaging. Databases of the shear stiffness of skeletal muscle have been presented in the relaxed and contracted states in the upper extremity (biceps brachii, flexor digitorum profundus, and upper trapezius), distal leg muscles (tibialis anterior, medial gastrocnemius, lateral gastrocnemius, and trapezius), and proximal leg muscles (vastus lateralis, vastus medialis, and sartorius). MRE measurements have successfully validated a mathematical model of skeletal muscle behavior in the biceps brachii, correlated to electromyographic data in the distal leg muscles and quantified the effects of pathologies on the distal and proximal leg muscles. Future research efforts should be directed toward improving one‐dimensional (1D) and 3D MRE data acquisition and image processing, tracking the effects of treatment on pathologic muscle and correlating the shear stiffness with clinical measurements. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Balanced SSFP imaging of the musculoskeletal system
Authors: Gold Garry E. , Hargreaves Brian A. , Reeder Scott B. , Block Walter F. , Kijowski Richard , Vasanawala Shreyas S. , Kornaat Peter R. , Bammer Roland , Newbould Rexford , Bangerter Neal K. , Beaulieu Christopher F.
Published: January 2007

Magnetic resonance imaging (MRI), with its unique ability to image and characterize soft tissue noninvasively, has emerged as one of the most accurate imaging methods available to diagnose bone and joint pathology. Currently, most evaluation of musculoskeletal pathology is done with two‐dimensional acquisition techniques such as fast spin echo (FSE) imaging. The development of three‐dimensional fast imaging methods based on balanced steady‐state free precession (SSFP) shows great promise to improve MRI of the musculoskeletal system. These methods may allow acquisition of fluid sensitive isotropic data that can be reformatted into arbitrary planes for improved detection and visualization of pathology. Sensitivity to fluid and fat suppression are important issues in these techniques to improve delineation of cartilage contours, for detection of marrow edema and derangement of other joint structures. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Magnetic resonance imaging of entheses using ultrashort TE (UTE) pulse sequences
Authors: Benjamin Michael , Bydder Graeme M
Published: January 2007

The attachment of tendons, ligaments, and joint capsule to bone (entheses) is reviewed and new options for visualizing key components of entheses provided by ultrashort TE (UTE) pulse sequences are described. Many features of entheses are adapted to the dispersion of stress at the boundary between tendons/ligaments and bone. Of particular interest is fibrocartilage, which has mechanical properties different from those of both “pure” tendon/ligament and bone. Features typical of entheses can also be seen at sites where tendons or ligaments are in contact with (but not attached to) bone, and the concept of a “functional enthesis” has been developed to emphasize the similarities. The enthesis concept has also been broadened to include the idea of an “enthesis organ” in which many tissues play a role in dissipating stress concentration. UTE pulse sequences can specifically identify the calcified and uncalcified fibrocartilage tissue components of entheses and differentiate these from fibrous connective tissue and bone. These tissues cannot be separately visualized at entheses with conventional pulse sequences. Entheses are involved in overuse syndromes and seronegative spondyloarthropathies (SpA) and there are important issues related to tissue repair and healing following surgery. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
The magic angle effect: A source of artifact, determinant of image contrast, and technique for imaging
Authors: Bydder Mark , Rahal Andres , Fullerton Gary D. , Bydder Graeme M.
Published: January 2007

This review provides a formalism for understanding magic angle effects in clinical studies. It involves consideration of the fiber‐to‐field angle for linear structures such as tendons, ligaments, and peripheral nerves, disc‐like and circular structures such as menisci and labra, as well as complex three‐dimensional structures. There may be one or more fiber types with different orientations within each of these tissues. The orientation of these fibers to B0 is crucial in determining their magic angle effect. Tissues may show a variety of appearances depending on their baseline T2, as well as the increase in T2 produced by the magic angle effect. The appearances are affected by TE, which affects both the general tissue signal level and the change in signal produced by the magic angle effect, fiber‐to‐slice orientation, and partial volume effects. Deliberate positioning of structures and tissues at particular orientations to B0 can be used to increase the signal from tissues such as tendons and ligaments and so allow them to be imaged with conventional sequences. The technique can also be used to produce contrast between tissues with fibers that have different orientations to B0. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Magnetic resonance imaging with ultrashort TE (UTE) PULSE sequences: Technical considerations
Authors: Tyler Damian J. , Robson Matthew D. , Henkelman R. Mark , Young Ian R. , Bydder Graeme M.
Published: January 2007

It is now possible to detect signals from tissues and tissue components with short T2s, such as cortical bone, using ultrashort TE (UTE) pulse sequences. The background to the use of these sequences is reviewed with particular emphasis on MR system issues. Tissue properties are discussed, and tissues are divided into those with a majority and those with a minority of short T2 components. UTE pulse sequences and their variants are described and clinical applications are illustrated. System design requirements for sequences of this type, including gradient performance, RF switching, and data‐processing issues, are outlined. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Low‐field musculoskeletal MRI
Authors: Ghazinoor Shaya , Crues John V. , Crowley Chris
Published: January 2007

Since it was first introduced in the field of medical imaging in the early 1980s, MRI has become essential for the diagnosis and treatment of musculoskeletal conditions. Most imaging in the United States is performed on high‐field (>1.0T), whole‐body scanners. However, for reasons discussed below, imaging at low (<0.5T) and medium (0.5–1.0T) field strengths using small, low‐cost, easily installed scanners in imaging centers and physicians' offices is gaining increasing popularity. Such scanners can be very useful for imaging the upper and lower extremities, from the shoulder to the fingers and the hips to the toes. In this review we provide an overview of the different available extremity scanners and their advantages and disadvantages, briefly review the literature regarding their use, and discuss our experience in using low‐field extremity scanners to evaluate joints. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Study of order and dynamic processes in tendon by NMR and MRI
Authors: Navon G. , Eliav U. , Demco D.E. , Blümich B.
Published: January 2007

Tendons are composed of a parallel arrangement of densely packed collagen fibrils that results in unique biomechanical properties of strength and flexibility. In the present review we discuss several advanced magnetic resonance spectroscopy (MRS) and imaging (MRI) techniques that have allowed us to better understand the biophysical properties of tendons and ligaments. The methods include multiple quantum and T2 filtering combined with NMR and MRI techniques. It is shown in detail how these techniques can be used to extract a number of useful parameters: 1) the 1H‐1H and 1H‐2H dipolar interactions; 2) the proton exchange rates between water and collagen, and between water molecules; 3) the distribution of fibril orientations; and 4) the anisotropy of diffusion. It is shown that relaxation data as a function of angular dependence can be obtained in vivo using mobile NMR sensors. Finally, this article describes how double quantum filtered (DQF) MRI can be used to image and monitor the healing process in injured tendons. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Developments in dynamic MR elastography for in vitro biomechanical assessment of hyaline cartilage under high‐frequency cyclical shear
Authors: Lopez Orlando , Amrami Kimberly K. , Manduca Armando , Rossman Phillip J. , Ehman Richard L.
Published: January 2007

The design, construction, and evaluation of a customized dynamic magnetic resonance elastography (MRE) technique for biomechanical assessment of hyaline cartilage in vitro are described. For quantification of the dynamic shear properties of hyaline cartilage by dynamic MRE, mechanical excitation and motion sensitization were performed at frequencies in the kilohertz range. A custom electromechanical actuator and a z‐axis gradient coil were used to generate and image shear waves throughout cartilage at 1000–10,000 Hz. A radiofrequency (RF) coil was also constructed for high‐resolution imaging. The technique was validated at 4000 and 6000 Hz by quantifying differences in shear stiffness between soft (∼200 kPa) and stiff (∼300 kPa) layers of 5‐mm‐thick bilayered phantoms. The technique was then used to quantify the dynamic shear properties of bovine and shark hyaline cartilage samples at frequencies up to 9000 Hz. The results demonstrate that one can obtain high‐resolution shear stiffness measurements of hyaline cartilage and small, stiff, multilayered phantoms at high frequencies by generating robust mechanical excitations and using large magnetic field gradients. Dynamic MRE can potentially be used to directly quantify the dynamic shear properties of hyaline and articular cartilage, as well as other cartilaginous materials and engineered constructs. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Pathophysiology of the intervertebral disc and the challenges for MRI
Authors: Urban Jill P.G. , Winlove C. Peter
Published: January 2007

Through its ability to make relatively noninvasive and repeatable measurements, MRI has a great deal to offer, not only to clinical diagnosis of intervertebral disc disorders but also as a tool for basic research into disc physiology and the etiology of disc degeneration. In this brief review we outline the structure of the disc, the composition and organization of its macromolecules, and the changes that occur during disc degeneration, attempting to summarize features that have been or could become targets of MRI characterization. It is important to recognize, however, the fundamental limitation that most of the changes so far observed in MRI are consequences of alterations in cellular metabolism that occurred months to years previously and provide little insight into the current functional status of the tissue. There is therefore a need to develop MR techniques that directly characterize cellular activity and factors such as nutrient delivery on which it is critically dependent. We therefore briefly review cellular energy metabolism and nutrient transport into the avascular disc and consider the ability of MRI to reveal information about such processes. As a corollary of this discussion we also consider the constraints that the unusual transport properties of the disc impose on the delivery of contrast agents to the disc, since an understanding of these limitations is central to interpretation of the resulting images. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Response to Preoperative Chemoembolization Correlates with Outcome After Liver Transplantation in Patients with Hepatocellular Carcinoma
Authors: Millonig Gunda , Graziadei Ivo W. , Freund Martin C. , Jaschke Werner , Stadlmann Sylvia , Ladurner Ruth , Margreiter Raimund , Vogel Wolfgang
Published: January 2007

Patients with small hepatocellular carcinoma (HCC) can be cured by liver transplantation (LT). However, many patients drop out during the waiting time as a result of tumor progression. We prospectively investigated the effect of transarterial chemoembolization on long-term survival of 116 patients with HCC listed for LT. Intention-to-treat analysis revealed that patients with either complete or partial response to therapy (no vital tumor or devascularization of ≥30%, respectively) as assessed by computed tomographic scan before LT had far better 1-, 2-, and 5-year survival rates (100, 93.2, and 85.7%; and 93.8, 83.6, and 66.2%, respectively) compared with those with no response or with tumor progression (82.4, 50.7, and 19.3%). Posttransplant survival analysis showed a marked survival benefit according to transarterial chemoembolization response: patients with complete or partial response had 1-, 2-, and 5-year survival rates of 89.1, 85.1, and 85.1%, and 88.6, 77.4, and 63.9%, respectively, compared with 68.6, 51.4, and 51.4% for patients whose disease did not respond to therapy. Subgroup analysis, however, showed that these benefits were only seen in patients whose disease met the Milan criteria, but not in disease exceeding the Milan criteria but fitting the expanded University of California at San Francisco criteria. These patients were also more likely to drop out as a result of tumor progression while waiting for LT (dropout rate 12.1 vs. 2.9%) and to develop recurrent HCC (21.6 vs. 7.6%). Downstaged patients did even worse, with a dropout rate of 26.7% and a 5-year survival rate of only 25%. In conclusion, the response to preoperative chemoembolization may predict long-term outcome after LT. Liver Transpl 13:272–279, 2007. © 2007 AASLD.
Abnormal temporal discrimination threshold in patients with multiple system atrophy
Authors: Lyoo Chul H. , Lee Seung Yeob , Song Tae Jin , Sik Lee Myung
Published: January 2007

The temporal discrimination threshold (TDT), the shortest time interval that allows two temporally separated successive stimuli to be perceived as two different stimuli, is a constituent of kinesthetic sensation. Intact kinesthesia is a necessity for well‐controlled voluntary movements. In patients with Parkinson's disease and dystonia, abnormally increased TDT has been reported and it may contribute to the pathophysiology of motor deficits. We explored the integrity and clinical significance of TDT in patients with multiple system atrophy (MSA). A total of 30 de novo patients with MSA and 11 age‐matched normal controls were included. The TDT values were measured in the feet with four different paradigms (ascending and descending interstimuli intervals; same and different point stimulation). The Unified Parkinson's Disease Rating Scale (UPDRS) Motor and the International Cooperative Ataxia Rating Scale (ICARS) scores were measured for parkinsonian and cerebellar deficits, respectively. Means of the TDT values of the patients with MSA were higher than those of the controls. The TDT values correlated with UPDRS Motor scores independent of ICARS scores. Among the parkinsonian motor deficits, only the UPDRS Motor subscores representing bradykinesia correlated with the TDT values. In patients with MSA, abnormal somatic sensory processing seems to be associated with damage to the nigrostriatal dopaminergic and/or striatal neurons. © 2007 Movement Disorder Society
Dystonia gravidarum: A new case with a long follow‐up
Authors: Fasano Alfonso , Elia Antonio E. , Guidubaldi Arianna , Tonali Pietro A. , Bentivoglio Anna Rita
Published: January 2007

We report a case of cervical dystonia occurring in a 33‐year‐old without personal history of movement disorder but with family history of essential tremor, primigravid, primiparous woman at 1 weeks' amenorrhea, resolved completely after delivery in the course of 3 months. Dystonia never recurred in the following 5 years. Several neurological disorders are known to occur or worsen during pregnancy. As far as we know, this is the second reported case of dystonia occurring during pregnancy, thus confirming that dystonia gravidarum represents a new entity and should be considered in women of reproductive age affected by dystonia, especially when presenting with rapid‐onset cervical dystonia. © 2007 Movement Disorder Society
Permanent lithium‐induced cerebellar toxicity: Three cases and review of literature
Authors: Niethammer Martin , Ford Blair
Published: January 2007

Lithium can have toxic effects on the central nervous system that are both acute and chronic. Uncommonly, a long‐lasting cerebellar syndrome follows acute toxicity. The mechanism of cerebellar injury is not well understood. We present 3 cases of this syndrome, with video demonstrating the typical features of this syndrome. © 2007 Movement Disorder Society
Evaluating posterolateral linearization of the putaminal margin with magnetic resonance imaging to diagnose the Parkinson variant of multiple system atrophy
Authors: Ito Shoichi , Shirai Wakako , Hattori Takamichi
Published: January 2007

The objective was to develop a simple method for evaluating putaminal atrophy in patients with the Parkinson variant of multiple system atrophy (MSA‐P). We used magnetic resonance imaging to study 9 patients with MSA‐P, 24 patients with cerebellar variants of multiple system atrophy (MSA‐C), 38 patients with Parkinson's disease (PD), and 27 healthy control subjects. Posterolateral linearization of the putaminal margin was semiquantitatively scored and the putaminal area per intracranial area was calculated as the adjusted putaminal area. There was a negative correlation between the linearization scores and adjusted putaminal areas (r = −0.43, P < 0.001), such that the mean adjusted putaminal area in the group without putaminal linearization (0.0148 ± 0.0022) was greater than that of the group with linearization (0.0124 ± 0.0029, P < 0.005). Moreover, the occurrence of putaminal linearization was significantly higher in MSA‐P patients (88.8%) than in MSA‐C (8.3%), PD (7.9%) and healthy subjects (7.4%; P < 0.005). Putaminal linearization was a highly sensitive (0.89) and specific (0.91) measure for differentiating MSA‐P. Our results suggest that evaluating posterolateral putaminal linearization is useful for assessing putaminal atrophy and for differentiating MSA‐P from MSA‐C, PD, and healthy subjects. © 2007 Movement Disorder Society