bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic Rhinometry and Rhinomanometry in the Evaluation of Nasal Patency of Patients with Nasal Septal Deviation
Authors: Szücs Eva , Clement Peter A. R.
Published: March 2007

The aim of the present study was to assess the clinical utility of acoustic rhinometry (AR) compared with active anterior rhinomanometry (AAR) in the evaluation of nasal patency in subjects with nasal septal deviation. Fifty patients were divided into three groups based upon the part of the nasal cavity where the septal deviation was situated (anterior: up to 2.5 cm; middle: between 2.5 and 4.5 cm; posterior: between 4.5 and 8 cm measured from the columella). The control group consisted of 15 subjects with no nasal complaints and no history of nasal disease. Inspiratory and expiratory nasal airway resistance (NAR) at 75 Pa and at 150 Pa before and after decongestion were measured by AAR. Minimal Cross-sectional Area (MCA), distance of MCA, and nasal volume (Vol) were measured before and after decongestion by AR (Rhino 2000). Subjective nasal patency was assessed by Visual Analogue Score (VAS). In the statistical analysis the deviated unilateral nasal cavities were compared with the randomly chosen unilateral nasal cavities of normal subjects. Both techniques AR and AAR were sufficiently sensitive to reveal severe deviations in the anterior nasal cavity (MCA, Volant, NAR75, NAR150, p < 0.05). The techniques were less sensitive in cases of middle and posterior deviations (MCA, Volmid, Volpost, MCAmid, MCApost, NAR75, p > 0.05). The nondecongested inspiratory and expiratory NAR at 150 Pa were the only parameter that differed from normal in cases of posterior deviations. The VAS correlated better with NAR than with MCA. MCA correlated more frequently with expiratory than with inspiratory NAR.
Clinical and molecular characterization of a patient with a 2q31.2‐32.3 deletion identified by array‐CGH
Authors: Mencarelli Maria Antonietta , Caselli Rossella , Pescucci Chiara , Hayek Giuseppe , Zappella Michele , Renieri Alessandra , Mari Francesca
Published: March 2007

We report on a patient with a de novo interstitial deletion of the long arm of chromosome 2 involving bands 2q31.2‐2q32.3. The patient shows severe mental retardation, absence of speech, sleep disturbances, behavioral problems, and some dysmorphic features. In particular, he presents with macrocephaly, high forehead, thick and coarse hair, thick eyebrows, synophrys, increased inner and outer canthal distance, bifid nasal tip, high palate, micrognathia, dysmorphic right ear, and long and tapering fingers. Array‐CGH analysis allowed us to identify and characterize a 2q interstitial deletion of about 13 Mb, involving the segment between cytogenetic bands 2q31.2 and 2q32.3. The deletion was confirmed by quantitative PCR. We compare the phenotype of our patient with those already reported in literature. In particular, we discuss the similarities shared with two recently reported patients, studied by array‐CGH, who show an overlapping deletion. The common clinical features are: long face, high forehead, abnormal teeth and ears, midface hypoplasia, high palate, micrognathia, transparent and thin skin, high frequency of inguinal hernia, severe development impairment, and behavioral problems. Some genes located in the deleted region may be good candidates for the neurological phenotype such as ZNF533 and MYO1B, which are both involved in neuronal function. Furthermore, the GLS gene could be a good candidate in generating the behavioral phenotype in the patient. In fact, it encodes for the major enzyme yielding glutamate from glutamine and it can be implicated in behavioral disturbances in which glutamate acts as a neurotransmitter. © 2007 Wiley‐Liss, Inc.
SNP fine mapping of chromosome 8q24 in bipolar disorder
Authors: Zandi Peter P. , Avramopoulos Dimitrios , Willour Virginia L. , Huo Yuqing , Miao Kuangyi , MacKinnon Dean F. , McInnis Melvin G. , Potash James B. , DePaulo J. Raymond
Published: March 2007

We previously reported linkage to chromosome 8q24 in bipolar disorder (BP) with a LOD of 3.32. We fine mapped the locus with SNPs and tested for association with BP in families with evidence of linkage to the region. We genotyped 249 informative SNPs over 3.4 Mb in an initial sample of 155 nuclear families (352 affected offsprings), and followed up the best findings by genotyping six of the most significantly associated SNPs in a replication sample of 103 nuclear families (231 affected offsprings). We used FBAT and GIST for association tests. Two clusters of SNPs emerged with the strongest evidence of association. The first consisted of three SNPs, approximately 3 kb 5′ from the gene ST3GAL1. These SNPs were associated with BP in the initial sample by FBAT (best P = 0.001) and GIST (best P = 0.05) and associated in the replication sample by FBAT (best P = 0.04). The second cluster consisted of four SNPs (one of which was not genotyped in the replication sample), approximately 480 kb 5′ of ST3GAL1 in a relative gene desert. These SNPs were associated with BP in the initial sample by FBAT (best P = 0.007) and GIST (best P = 0.03), and marginally associated in the replication sample by FBAT (best P = 0.07) and GIST (P = 0.04). ST3GAL1 belongs to a family of glycosyltransferase proteins, several members of which are highly expressed in the brain and involved in neurogenesis. Several other interesting candidate genes are also located nearby. The congruence of findings across methods and samples suggests further investigation is warranted in these two targeted regions. © 2007 Wiley‐Liss, Inc.
Thermal degradation and ageing behavior of microcomposites of natural rubber, carboxylated styrene butadiene rubber latices, and their blends
Authors: Stephen Ranimol , Siddique A. M. , Singh Fouran , Kailas Lekshmi , Jose Seno , Joseph Kuruvilla , Thomas Sabu
Published: March 2007

The effect of microfillers on the thermal stability of natural rubber (NR), carboxylated styrene butadiene rubber (XSBR) latices, and their 70/30 NR/XSBR blend were studied using thermogravimetric method. Microcomposites of XSBR and their blend were found to be thermally more stable than unfilled samples. The activation energy needed for the degradation of polymer chain was calculated from Coats‐Redfern plot. Activation energy needed for the thermal degradation of filled samples was higher than unfilled system. It indicated the improved thermal stability of the filled samples. The ageing resistance of the micro‐filled samples was evaluated from the mechanical properties of aged samples. The thermal ageing was carried out by keeping the samples in hot air oven for 7 days at 70°C. The mechanical properties such as tensile strength, modulus at 300% elongation, and strain at break were computed. As compared to unfilled samples, micron‐sized fillers reinforced systems exhibited higher ageing resistance. Finally, an investigation was made on the influence of ion‐beam irradiation on microcomposites of NR, XSBR latices, and their 70/30 blend systems using 28Si8+ performed at 100 MeV. The surface changes of the samples after irradiation were analyzed using X‐ray photoelectron spectroscopy. The results of XPS measurements revealed that the host elements were redistributed without any change in binding energies of C1s, O1s, and Si2p. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Percutaneous closure of an aortic paravalvular leak via the transradial approach
Authors: Hildick‐Smith D. , Behan M.W.H. , De Giovanni J.
Published: March 2007

Percutaneous closure of aortic and mitral paraprosthetic leaks using the Amplatzer Occluders (muscular ventricular septal defect occluder) is now a well recognized procedure although as “off label” use. Aortic paravalvular leak closure is usually carried out via transfemoral puncture, but problems with this approach include the need to stop warfarin and the inadequate length of standard delivery sheaths. We report the first case of percutaneous aortic paravalvular leak closure through via the transradial route. © 2007 Wiley‐Liss, Inc.
Allele Specific C‐Bulge Probes with One Unique Fluorescent Molecule Discriminate the Single Nucleotide Polymorphism in DNA
Authors: Takei Fumie , Suda Hitoshi , Hagihara Masaki , Zhang Jinhua , Kobori Akio , Nakatani Kazuhiko
Published: March 2007

A combination of an allele specific C‐bulge probe and the fluorescent molecule N,N′‐bis(3‐aminopropyl)‐2,7‐diamino‐1,8‐naphthyridine (DANP) that binds specifically to the C‐bulge provides a method for single nucleotide polymorphism (SNP) typing with only one fluorescent molecule without covalent modification of the DNA probe. The allele specific C‐bulge probe contains one additional cytosine and produces a C‐bulge directly flanking the SNP site upon hybridization to the target DNA. The C‐bulge is a scaffold to recruit and retain DANP directly neighboring the SNP site. The DANP fluorescent probe was selectively modulated by the flanking matched and mismatched base pairs. The mutation type could be discriminated by the modulated fluorescent intensity with respect to the allele specific C‐bulge probes used for the assay.
Mutual kinetic separation of isotopomers of pentafluorophenyl 2‐phenyl propionate using quasi‐enantiomeric oxazolidinones
Authors: Chavda Sameer , Coumbarides Gregory S. , Dingjan Marco , Eames Jason , Flinn Anthony , Northen Julian
Published: March 2007

Mutual separation of an equimolar mixture of quasi‐enantiomeric [D,13C]‐labeled isotopomers of pentafluorophenyl 2‐phenylpropionate can be achieved efficiently by use of two quasi‐enantiomeric Evans' oxazolidinones. The levels of stereocontrol were high, leading to products with predictable configurations. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Chiral crystallization of glutamic acid on self assembled films of cysteine
Authors: Dressler David H. , Mastai Yitzhak
Published: March 2007

In this article, we describe the preparation and use of chiral surfaces derived from enantiomerically pure crystals of amino acids. For this purpose, we chose to employ a self‐assembly process to grow nanoscale chiral films of (+)‐l or (−)‐d cysteine, onto gold surfaces. We utilized those chiral films as resolving auxiliaries in the crystallization of enantiomers from solutions. To demonstrate the chiral discriminating ability of the chiral surfaces in crystallization processes, we investigated the crystallization of rac‐glutamic acid onto the chiral films. Our study demonstrates the potential application of chiral films to control chirality throughout crystallization, where one enantiomer crystallizes on the chiral surfaces with relatively high enantiomeric excess. In addition, crystallization of pure glutamic acid enantiomers, and its racemic compound on to chiral films resulted in crystal morphology modification with preferred crystal orientation, which assists in the interpretation of the ability of our chiral surfaces to function as chiral selectors. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Microtubules' interaction with cell cortex is required for their radial organization, but not for centrosome positioning
Authors: Brodsky I. B. , Burakov A. V. , Nadezhdina E. S.
Published: March 2007

Microtubules in interphase mammalian cells usually form a radial array with minus‐ends concentrated in the central region and plus‐ends placed at the periphery. This is accepted as correct, that two factors determinate the radial organization of microtubules ‐ the centrosome, which nucleate and anchor the microtubules minus‐ends, and the interaction of microtubules with cortical dynein, which positions centrosome in the cell center. However, it looks as if there are additional factors, affecting the radial structure of microtubule system. We show here that in aged Vero cytoplasts (17 h after enucleation) microtubule system lost radial organization and became chaotic. To clear up the reasons of that, we studied centrosome activity, its position in the cytoplasts and microtubule dynamics. We found that centrosome in aged cytoplasts was still active and placed in the central region of the cytoplasm, while after total disruption of the microtubules it was displaced from the center. Microtubules in aged cytoplasts were not stabilized, but they lost their ability to stop to grow near cell cortex and continued to grow reaching it. Aged cytoplast lamellae was partially depleted with dynactin though Golgi remained compact indicating dynein activity. We conclude that microtubule stoppage at cell cortex is mediated by some (protein) factors, and these factors influence radial structure of microtubule system. It seems that the key role in centrosome positioning is played by dynein complexes anchored everywhere in the cytoplasm rather than anchored in cell cortex. Cell Motil. Cytoskeleton 2007. © 2007 Wiley‐Liss, Inc.
Centralization of care for patients with advanced‐stage ovarian cancer
Authors: Bristow Robert E. , Santillan Antonio , Diaz‐Montes Teresa P. , Gardner Ginger J. , Giuntoli Robert L. , Meisner Benjamin C. , Frick Kevin D. , Armstrong Deborah K.
Published: March 2007

BACKGROUND.

The objective of this study was to evaluate the cost‐effectiveness of centralized referral of patients with advanced‐stage epithelial ovarian cancer who underwent primary cytoreductive surgery and adjuvant chemotherapy.

METHODS.

A decision‐analysis model was used to compare 2 referral strategies for patients with advanced‐stage ovarian cancer: 1) referral to an expert center, with a rate of optimal primary cytoreduction of 75% and utilization of combined intraperitoneal and intravenous adjuvant chemotherapy, and 2) referral to a less experienced center, with a rate of optimal primary cytoreduction of 25% and adjuvant treatment that consisted predominantly of intravenous chemotherapy alone. The cost‐effectiveness of each strategy was evaluated from the perspective of society.

RESULTS.

A cost‐effectiveness analysis revealed that the strategy of expert center referral had an overall cost per patient of $50,652 and had an effectiveness of 5.12 quality‐adjusted life years (QALYs). The strategy of referral to a less experienced center carried an overall cost of $39,957 and had an effectiveness of 2.33 QALYs. The expert center strategy was associated with an additional 2.78 QALYs at an incremental cost of $10,695 but was more cost‐effective, with a cost‐effective ratio of $9893 per QALY compared with $17,149 per QALY for the less experienced center referral strategy. Sensitivity analyses and a Monte Carlo simulation confirmed the robustness of the model.

CONCLUSIONS.

According to results from the decision‐analysis model, centralized referral of patients with ovarian cancer to an expert center was a cost‐effective healthcare strategy and represents a paradigm for quality cancer care, delivering superior patient outcomes at an economically affordable cost. Increased efforts to align current patterns of care with a universal strategy of centralized expert referral are warranted. Cancer 2007. © 2007 American Cancer Society.
Assessment of prognosis with the total illness burden index for prostate cancer
Authors: Litwin Mark S. , Greenfield Sheldon , Elkin Eric P. , Lubeck Deborah P. , Broering Jeanette M. , Kaplan Sherrie H.
Published: March 2007

BACKGROUND.

Among the most pressing challenges that face physicians who care for men with prostate cancer is evaluating the patient's potential for benefiting from treatment. Because prostate cancer often follows an indolent course, the presence and severity of comorbidities may influence the decision to treat the patient aggressively. The authors adapted the Total Illness Burden Index (TIBI) for use in decision‐making among men with prostate cancer at the time of the visit.

METHODS.

An observational study was performed of 2894 participants in the Cancer of the Prostate Strategic Urologic Research Endeavor, a national disease registry of men with prostate cancer, to examine how well the adapted TIBI for prostate cancer (TIBI‐CaP) predicted mortality over the subsequent 3.5 years and health‐related quality of life over the subsequent 6 months.

RESULTS.

The men who had the highest global TIBI‐CaP scores were 13 times more likely to die of causes other than prostate cancer over a 3.5‐year period than the men who had the lowest scores (hazard ratio, 13.1, 95% confidence interval, 6.3–27.4) after controlling for age, education, income, and race/ethnicity. Patients who had the highest TIBI‐CaP scores had 44% mortality compared with 4.9% mortality for patients who had the lowest scores. Demographic variables explained 16% of the variance in future physical function; TIBI‐CaP scores explained an additional 19% of the variance.

CONCLUSIONS.

The TIBI‐CaP, a patient‐reported measure of comorbidity, identified patients at high risk for nonprostate cancer mortality. It predicted both mortality and future quality of life. The TIBI‐CaP may aid physicians and patients in making appropriate treatment decisions. Cancer 2007. © 2007 American Cancer Society.
Glycemic control is related to the severity of impaired thermal sensations in type 2 diabetes
Authors: Chao Chi‐Chao , Hsieh Song‐Chou , Yang Wei‐Shiung , Lin Yea‐Hui , Lin Whei‐Min , Tai Tong‐Yuan , Hsieh Sung‐Tsang
Published: March 2007

Background

Small‐fibre sensory neuropathy of diabetes presenting as impaired thermal sensations is associated with ominous consequences, such as foot ulcer and amputation, but there is a lack of systematic studies on its occurrence in large cohorts. We investigated (1) the impact of glycemic control on thermal thresholds, (2) the frequencies and patterns of sensory deficits, and (3) the contribution of sensory nerve abnormalities to neuropathic symptoms.

Methods

Quantitative sensory testing and nerve conduction studies were performed to measure warm and cold thresholds of extremities, and amplitudes of nerve action potentials on 498 type 2 diabetic patients and 434 control subjects with similar age and gender distributions, enrolled during the same period.

Results

The diabetic patients had higher thermal thresholds than control subjects (p < 0.0001). Thermal thresholds of the lower and upper extremities were linearly correlated with HbA1C on multiple linear regression analysis (p < 0.01). By the multivariate logistic regression analysis, HbA1C and age were the most important risk factors independently associated with elevated thermal thresholds (p < 0.01). Elevated warm threshold in the big toe was the most frequent abnormality (60.2%) compared to abnormal cold threshold in the big toe (39.6%) and abnormal sural nerves on nerve conduction studies (12.9%). Elevated thermal thresholds were risk factors for neuropathic symptoms independent of HbA1C.

Conclusion

Small‐fibre neuropathy with the impairment of thermal sensations is the most frequent sensory deficit in diabetes, and HbA1C is significantly associated with the elevated thermal thresholds. Copyright © 2007 John Wiley & Sons, Ltd.
Copper(II)–Purine Complexes Encapsulated in NaY Zeolite
Authors: Nunes Natércia , Amaro Raquel , Costa Filomena , Rombi Elisabetta , Carvalho M. Alice , Neves Isabel C. , Fonseca António M.
Published: March 2007

Y‐encapsulated CuII–purine complexes were synthesized, characterized and studied in the catalytic oxidation of cyclohexene. Encapsulation was achieved by ion‐exchanging the complex from aqueous solutions containing both the purine ligand, 9‐methyl‐6‐(methylamino)purine, and copper, in different pH, with a purine/CuII molar ratio of 5:1. The resulting materials were characterized by surface analysis (XPS, SEM and XRD), chemical analysis, spectroscopic methods (EPR, FTIR and UV/Vis) and thermal analysis (TGA), which indicated that the CuII–purine complexes were effectively encapsulated in NaY, most probably inside the supercages, without any modification of the morphology and structure of the zeolite. Different CuII–purine complexes were formed, depending on the pH during synthesis. The coordination geometry of Y‐encapsulated CuII–purine complexes was obtained with preferentially 1:2 and 1:3 Cu/L stoichiometry: complexes A and B (1:2) and complex C (1:3). Complex A was formed at pH ≥ 7, and complexes B and C (Scheme 2) were formed at pH = 5.4. Oxidation of cyclohexene with tBuOOH (TBHP) as the oxygen source, gave 2‐cyclohexene‐1‐one, 2‐cyclohexene‐1‐ol, cyclohexene oxide and 3‐tert‐butylcyclohexenyl peroxide. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Comparison between the Photophysical Properties of Pyrazolo‐ and Isoxazolo[60]fullerenes with Dual Donors (Ferrocene, Aniline and Alkoxyphenyl)
Authors: Perez Laura , El‐Khouly Mohamed E. , de la Cruz Pilar , Araki Yasuyuki , Ito Osamu , Langa Fernando
Published: March 2007

Two series of new pyrazolo‐ and isoxazolo[60]fullerenes covalently linked to vinylenephenylene bearing ferrocene, dibutylaniline or dodecyloxyphenyl electron‐donor groups attached in the periphery have been synthesized. The photophysical properties of these newly synthesized dual‐donor–C60 derivatives have been investigated and compared by applying time‐resolved fluorescence and nanosecond transient techniques in both polar and nonpolar solvents. Charge separation via the excited singlet state of C60 is more efficient in the pyrazolo‐C60 triads than in the isoxazolo‐C60 triads. It was found that the pyrazoline ring mediates charge separation as a result of the stronger electron‐donating character of the nitrogen atom of the pyrazoline ring compared with the oxygen atom of the isoxazoline ring. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
An Environmentally Friendly Oxidation System for the Selective Oxygenation of Aldimines to Oxaziridines with Anhydrous TBHP and Alumina‐Supported MoO3 as a Recyclable Heterogeneous Catalyst
Authors: Singhal Sweety , Jain Suman L. , Prasad V. V. D. N. , Sain Bir
Published: March 2007

A highly efficient and selective protocol for the oxygenation of various aldimines to oxaziridines, which proceeds in excellent yields with enhanced selectivity by using alumina‐supported MoO3 as a recyclable heterogeneous catalyst and anhydrous TBHP as the ultimate oxidant, is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Inhibition of glutamine transport into mitochondria protects astrocytes from ammonia toxicity
Authors: Pichili V. B. R. , Rao K. V. Rama , Jayakumar A. R. , Norenberg M. D.
Published: March 2007

Hepatic encephalopathy (HE) is a major neurological complication that occurs in the setting of severe liver failure. Ammonia is a key neurotoxin implicated in this condition, and astrocytes are the principal neural cells histopathologically and functionally affected. Although the mechanism by which ammonia causes astrocyte dysfunction is incompletely understood, glutamine, a by‐product of ammonia metabolism, has been strongly implicated in many of the deleterious effects of ammonia on astrocytes. Inhibiting mitochondrial glutamine hydrolysis in astrocytes mitigates many of the toxic effects of ammonia, suggesting the involvement of mitochondrial glutamine metabolism in the mechanism of ammonia neurotoxicity. To determine whether mitochondriaare indeed the organelle where glutamine exerts its toxic effects, we examined the effect of L‐histidine, an inhibitor of mitochondrial glutamine transport, on ammonia‐mediated astrocyte defects. Treatment of cultured astrocytes with L‐histidine completely blocked or significantly attenuated ammonia‐induced reactive oxygen species production, cell swelling, mitochondrial permeability transition, and loss of ATP. These findings implicate mitochondrial glutamine transport in the mechanism of ammonia neurotoxicity. © 2007 Wiley‐Liss, Inc.
ATP‐induced chemotaxis of microglial processes requires P2Y receptor‐activated initiation of outward potassium currents
Authors: Wu Long‐Jun , Vadakkan Kunjumon I. , Zhuo Min
Published: March 2007

Microglial cells are the resident macrophages that are involved in brain injuries and infections. Recent studies using transcranial two‐photon microscopy have shown that ATP and P2Y receptors mediated rapid chemotactic responses of miroglia to local injury. However, the molecular mechanism for microglial chemotaxis toward ATP is still unknown. To address this question, we employed a combination of simultaneous perforated whole‐cell recordings and time‐lapse confocal imaging in GFP‐labeled microglia in acute brain slices from adult mice. We found that ATP‐induced rapid chemotaxis is correlated with P2Y receptor associated‐outward potassium current in microglia. Activation of both P2Y receptor and its associated potassium channels are required for ATP‐induced chemotaxis and baseline motility of microglial cells. The chemotaxis required the activation of phosphoinositide 3‐kinase but not mitogen‐activated protein kinase pathway. Our results provide strong evidence that P2Y receptor‐associated outward potassium channels and the phosphoinositide 3‐kinase pathway are important for ATP‐induced microglial motility in acute brain slices. © 2007 Wiley‐Liss, Inc.
Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers
Authors: Susuki Keiichiro , Baba Hiroko , Tohyama Koujiro , Kanai Kazuaki , Kuwabara Satoshi , Hirata Koichi , Furukawa Keiko , Furukawa Koichi , Rasband Matthew N. , Yuki Nobuhiro
Published: March 2007

Paranodal axo‐glial junctions are important for ion channel clustering and rapid action potential propagation in myelinated nerve fibers. Paranode formation depends on the cell adhesion molecules neurofascin (NF) 155 in glia, and a Caspr and contactin heterodimer in axons. We found that antibody to ganglioside GM1 labels paranodal regions. Autoantibodies to the gangliosides GM1 and GD1a are thought to disrupt nodes of Ranvier in peripheral motor nerves and cause Guillain‐Barré syndrome, an autoimmune neuropathy characterized by acute limb weakness. To elucidate ganglioside function at and near nodes of Ranvier, we examined nodes in mice lacking gangliosides including GM1 and GD1a. In both peripheral and central nervous systems, some paranodal loops failed to attach to the axolemma, and immunostaining of Caspr and NF155 was attenuated. K+ channels at juxtaparanodes were mislocalized to paranodes, and nodal Na+ channel clusters were broadened. Abnormal immunostaining at paranodes became more prominent with age. Moreover, the defects were more prevalent in ventral than dorsal roots, and less frequent in mutant mice lacking the b‐series gangliosides but with excess GM1 and GD1a. Electrophysiological studies revealed nerve conduction slowing and reduced nodal Na+ current in mutant peripheral motor nerves. The amounts of Caspr and NF155 in low density, detergent insoluble membrane fractions were reduced in mutant brains. These results indicate that gangliosides are lipid raft components that contribute to stability and maintenance of neuron‐glia interactions at paranodes. © 2007 Wiley‐Liss, Inc.
Significance of IgG and IgM HCV antibody secretion in vitro in patients with chronic hepatitis C: Correlation with disease activity and response to interferon-α
Authors: Löhr Hanns , Nagel Christopher , Dienes Hans-Peter , Simpson Barry , Michel Gerd , Goergen Bernd , Zum Büschenfelde Karl-Hermann Meyer , Gerken Guido
Published: March 2007

Hepatitis C virus antibodies are found in the serum of most patients with chronic hepatitis C. However, the significance of the humoral response is still uncertain. In this study, in vitro IgG and IgM anti-hepatitis C virus secretion by peripheral blood mononuclear cells of patients with chronic hepatitis C was analyzed. Peripheral-blood mononuclear cells from 21 of 36 patients (58.3%) secreted IgG anti-hepatitis C virus in vitro, as demonstrated with anti-hepatitis C virus—specific enzyme immunoassays and recombinant immunoblot assays. Ten of the 36 patients (27.8%) showed both IgG and IgM anti-hepatitis C virus core in vitro. In 9 of these 10 patients, IgM anti-hepatitis C virus was also detected in serum. Patients with in vitro IgM or IgG anti-hepatitis C virus secretion had higher ALT levels in serum than did patients without such secretion in vitro (99.5 ± 22.1 and 85.6 ± 34.4 vs. 38.1 ± 37.4 U/L; p < 0.0001, p < 0.001). Furthermore, with a histology activity score it was demonstrated that patients with in vitro IgM or IgG HCV antibodies (or both) had more severe chronic active hepatitis than did patients without in vitro hepatitis C virus antibody secretion (p < 0.01). To analyze the therapy outcome, we included in this study 18 patients who had received interferon-α previously. Seven of eight in vitro hepatitis C virus antibody—positive patients were nonresponders, whereas the in vitro hepatitis C virus antibody—negative patients were mostly complete therapy responders (8 of 10). The follow-up study of eight patients with chronic hepatitis C after the beginning of therapy revealed that interferon-α decreases the in vitro humoral response to hepatitis C virus in treatment responders. In conclusion, this study demonstrates (a) in vitro secretion of IgG and IgM hepatitis C virus antibodies in patients with chronic hepatitis C, (b) that higher disease activity and persistent hepatitis C virus replication may be associated with ongoing antibody production in vitro and (c) in vitro antibody production seems to correlate negatively with the response of patients to antiviral treatment with interferon-α. (Hepatology 1994;20:1383-1389).
Prednisone-interferon combination in the treatment of chronic hepatitis B: Direct and indirect metanalysis
Authors: Cohard Marielle , Poynard Thierry , Mathurin Philippe , Zarski Jean Pierre
Published: March 2007

The aim of this study was to review all published randomized clinical trials evaluating the efficacy of a combination of prednisone and interferon in treatment of chronic hepatitis B and to subject these studies to metanalysis. Two types of metanalyses were carried out: direct metanalysis, comparing the prednisone-interferon combination with interferon on its own; and indirect metanalysis, comparing the treatment efficacy of prednisone-interferon and of interferon with control results. At the end of follow-up, four assessable end points were analyzed: HBeAg, hepatitis B virus DNA, HBsAg loss and serum ALT normalization rate. The direct metanalysis included seven trials comparing prednisone-interferon with interferon treatment. No significant differences were observed between the two types of therapy, for all the criteria given. However, in patients with low ALT levels, the prednisone-interferon combination gave significantly better results than interferon alone-HBeAg loss was 48% in the former group vs. 18.4% with interferon alone (p < 0.01). Fifteen trials compared interferon with control values; all end points were significantly improved. Seven trials compared prednisone-interferon with control results and showed all end points to be significantly improved by treatment. Indirect metanalysis showed that the differences in odds ratios for prednisone-interferon/control group and interferon/control group studies were negative for all assessable end points. In conclusion, the use of corticosteroids did not produce any significant increase in the efficacy of interferon treatment in adults with chronic hepatitis B and high initial ALT levels. However, it is possible that corticosteroids increased the HBeAg loss in the group of patients with low ALT levels. (Hepatology 1994;20:1390-1398).
Hepatic and extrahepatic hepatitis C virus replication in relation to response to interferon therapy
Authors: Saleh Mohamed G. , Tibbs Christopher J. , Koskinas John , Pereira Leila M. M. B. , Bomford Adrian B. , Portmann Bernard C. , McFarlane Ian G. , Williams Roger
Published: March 2007

Response to a 1-yr course of interferon-α2b was assessed in 18 patients with chronic hepatitis C virus infection in relation to clinical, biochemical and histological parameters and to the presence or absence of hepatitis C virus RNA and the presumed replicative form of the virus (negative-strand hepatitis C virus RNA) in serum, liver and peripheral blood mononuclear cells. The findings were compared with those in seven untreated patients studied over the same period. At the start of the study, positive-strand hepatitis C virus RNA was found in sera of all 25 patients, in livers of 24 and in peripheral-blood mononuclear cells of 19 of 22 tested; negative strand was found in livers of 11 and in peripheral-blood mononuclear cells of 15 of 22. Negative-strand hepatitis C virus RNA was not found in the serum of any patient at any stage. All of the five treated patients considered to show complete response during the study period cleared hepatic hepatitis C virus RNA, and four also became seronegative, but three had evidence suggestive of viral replication in their peripheral-blood mononuclear cells; two of these last patients subsequently relapsed. Loss of hepatic hepatitis C virus RNA was the only significant difference between these five and the seven partial and six nonresponders, but it is uncertain whether the observed changes were due specifically to interferon-induced modulation of virus expression because similar (apparently spontaneous) changes were seen in four of the untreated patients. Although we noted a significant tendency for patients with milder disease at the outset to respond to interferon, histological severity of disease did not correlate with hepatitis C virus RNA parameters, none of which was predictive of response to treatment. The findings suggest that the presence and replication of the virus at extrahepatic sites may be the crucial factor in resistance to interferon therapy. (Hepatology 1994;20:1399-1404).
Prognostic factors for hepatocellular carcinoma in genetic hemochromatosis
Authors: Fargion Silvia , Fracanzani Anna Ludovica , Piperno Alberto , Braga Mario , D'Alba Roberta , Ronchi Guido , Fiorelli Gemino
Published: March 2007

To identify factors that might be useful as prognostic indexes for the risk of hepatocellular carcinoma in Italian patients with genetic hemochromatosis, 152 homozygotes were studied prospectively for 1 to 229 mo. Factors that were considered in estimating the risk of developing hepatocellular carcinoma were age, sex, cirrhosis (Child class), HBsAg, antibodies to HBsAg, antibodies to HBcAg, hepatitis C antibodies, alcohol abuse and the amount of iron removed during therapeutic phlebotomy to produce iron depletion. At diagnosis, cirrhosis was present in 97 patients and absent in 55. During follow-up, hepatocellular carcinoma developed in 28 of the 97 patients with cirrhosis but in none of those without. Among patients with cirrhosis, the cumulative probability of being free of hepatocellular carcinoma at 10 yr was 70%. For patients with and without HBsAg the probabilities of being free of liver cancer at 10 yr were, respectively, 54% and 75%; for those with and without history of alcoholism, 58% and 78%; and for those younger and older than 55 yr, 90% and 54%. In patients with cirrhosis, multivariate analysis using proportional-hazards (Cox) regression found that the only factors contributing significantly to the estimation of a prognostic index were age, presence of HBsAg and alcohol abuse. Age over 55 yr increased the relative risk of hepatocellular carcinoma 13.3-fold (p < 0.001), the presence of HBsAg increased it 4.9-fold (p < 0.02) and alcohol abuse increased it 2.3-fold (p < 0.04). Homozygotes for genetic hemochromatosis with cirrhosis who were older than 55 yr had a history of alcohol abuse and were positive for HBsAg at the time of diagnosis had a 150 times higher relative risk of hepatocellular carcinoma. (Hepatology 1994;20:1426-1431).
Portal and gastric mucosal hemodynamics in cirrhotic patients with portal-hypertensive gastropathy
Authors: Ohta Masayuki , Higashi Makoto Hashizume Hidefumi , Ueno Kiichiro , Tomikawa Morimasa , Kishihara Fumiaki , Kawanaka Hirofumi , Tanoue Kazuo , Sugimachi Keizo
Published: March 2007

Controversy exists as to the nature of gastric perfusion in portal-hypertensive gastropathy. To investigate portal hemodynamics and gastric mucosal perfusion in cirrhotic patients with and without portalhypertensive gastropathy, we subjected 56 cirrhotic patients with portal hypertension to portal vein catheterization, pneumatic pressure sensor technique, duplex sonography and laser Doppler flowmetry. Thirteen patients had portal-hypertensive gastropathy: In 10 it was mild, and in 3 it was severe. The presence of portal-hypertensive gastropathy seemed to be independent of age, sex, cause of cirrhosis or grade of esophageal varices. Portal venous pressure, esophageal variceal pressure, portal venous flow and congestion index in patients with portal-hypertensive gastropathy were not significantly different from the values in those without portal-hypertensive gastropathy. However, portal-variceal pressure gradient (subtracting esophageal variceal pressure from portal venous pressure) (p < 0.01) and the incidence of palisading-type esophageal varices on portography (p < 0.05) was increased in patients with portalhypertensive gastropathy significantly more than in those without portal-hypertensive gastropathy. In the fundus, gastric mucosal blood flow was significantly higher in patients with portal-hypertensive gastropathy than in those without portal-hypertensive gastropathy, whereas in the corpus and the antrum the values were not significantly different. We suggest that the mucosa of the upper stomach in patients with portal-hypertensive gastropathy is congestive and highly perfused. The pathogenesis of portal-hypertensive gastropathy may be related to both congestion and hyperemia in the upper stomach. (Hepatology 1994;20:1432-1436).
Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis
Authors: Moradpour Darius , Altorfer Josef , Flury Renata , Greminger Peter , Meyenberger Christa , Jost Res , Schmid Martin
Published: March 2007

We describe a 33-yr-old pregnant woman in whom a primary biliary cirrhosis—like syndrome developed after 2 wk of chlorpromazine therapy. The clinical course was characterized by severe jaundice lasting 22 mo, intense pruritus, fever, steatorrhea, high alkaline phosphatase levels and hypercholesterolemia. Jaundice resolved with initiation of ursodeoxycholic acid therapy, but subclinical cholestasis and low-level inflammatory activity persisted and ultimately evolved into biliary cirrhosis. The pathological substrate of this severe and prolonged cholestatic reaction was found to be the vanishing bile duct syndrome with a marked transient pseudoxanthomatosis. (Hepatology 1994;20:1437-1441).
Daily determination of individual serum bile acids allows early detection of hepatic allograft dysfunction
Authors: Azer Samy A. , McCaughan Geoffrey W. , Stacey Neill H.
Published: March 2007

Acute graft rejection is still a major cause of morbidity after orthotopic liver transplantation, and its diagnosis necessitates an invasive liver biopsy. Our aim has been to determine whether changes in individual serum bile acid levels after engraftment are sensitive, specific and reliable indicators of graft function and whether these changes can antedate other biochemical indicators of hepatic allograft rejection. Individual bile acids in 200 serum samples taken serially from eight adult liver transplant patients were measured. Patients with biopsy-confirmed graft dysfunction due to rejection or nonrejection causes (n = 6 episodes) had significantly higher serum concentrations of glycocholate plus glycochenodeoxycholate and taurocholate/taurochenodeoxycholate ratios than did noncomplicated grafts (n = 3). These changes antedated any other conventional biochemical parameters by at least 48 hr and were 100% sensitive and specific. None of the conventional liver function tests could match this. Acute rejection episodes (n = 3) were then compared with nonrejection causes of graft dysfunction (n = 3). In acute rejection we noted a significant increase in the concentration of glycodeoxycholate plus deoxycholate and a significant decrease in the cholate/chenodeoxycholate ratio compared with that in nonrejection graft malfunction. Both of these changes antedated any other biochemical parameters by 24 hr. In conclusion, individual serum bile acid assays, after orthotopic liver transplantation, can detect graft dysfunction resulting from any cause at an earlier time than routine biochemical tests, and they are sensitive, specific and reliable for early detection of graft dysfunction. In addition, acute rejection can be distinguished from other causes of graft dysfunction.
Phospholipid antibodies in alcoholic liver disease
Authors: Chedid Antonio , Chadalawada Kurmanadha R. , Morgan Timothy R. , Moritz Thomas E. , Mendenhall Charles L. , Hammond James B. , Emblad Peter W. , Cifuentes Doris C. , Kwak Joanne W. H. , Gilman-Sachs Alice , Beaman Kenneth D.
Published: March 2007

Alcoholic liver injury has been reported to be directed preferentially against the proteins of the cell membrane, sparing the phospholipids. However, antiphospholipid antibodies against certain cell membrane phospholipids are known to be associated with a variety of diseases. We undertook this investigation to determine whether antiphospholipid antibodies were present in the serum of patients with alcoholic liver disease. We investigated seventy long-term alcoholic patients (> 80 gm ethanol/day for > 1 yr) and 8 normal nonalcoholic controls by means of enzyme-linked immunosorbent assay to determine whether serum antibodies were generated against the following membrane phospholipids: phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin) and phosphatidic acid. Group 1 comprised alcoholic patients with normal liver function (n = 13), group 2 comprised alcoholic patients with abnormal liver function (n = 16), group 3 comprised patients with alcoholic hepatitis or cirrhosis (n = 41) and group 4 comprised nonalcoholic controls (n = 8). The antibody prevalence was 15% in group 1, 31% in group 2, 81% in group 3 and 0% in group 4. In group 3, 20 of 41 patients had antibodies against several cell membrane phospholipids (i.e., phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidic acid, cardiolipin and phosphatidylinositol). The antiphosphatidylethanolamine isotype was IgA or IgM in 25 of 41 of these patients. Both IgA (p < 0.01) and IgM (p < 0.008) antiphosphatidylethanolamine correlated significantly with disease severity. Antiphospholipid antibodies in alcoholic patients seem to reflect disease progression and correlate significantly with disease severity.
Characteristics and regulation of bile salt synthesis and secretion by human hepatoma HepG2 cells
Authors: Cooper Allen D. , Craig Wendy Y. , Taniguchi Takahiro , Everson Gregory T.
Published: March 2007

Bile salt uptake, synthesis and secretion by the human hepatoma—derived cell line HepG2 were studied. The cells transported and secreted bile salts largely by means of passive mechanisms. The cells synthesized and secreted the normal human primary bile salts. The ratio of cholate to chenodeoxycholate was 1.5:1. The degree of conjugation, about 35%, was lower than normal, and the glycine-to-taurine ratio was abnormal (4.5:1). This was not due to amino acid deficiency in the medium. Contrary to the report of others, little 3α, 7α, 12α-trihydroxy-5β-cholestan-26-oic acid was secreted. This was confirmed by gas chromatography—mass spectrometry. The total rate of synthesis was about 33% that of normal liver. The specific activity of bile salts synthesized from [3H]mevalonate was about 20 times higher than that of the cellular cholesterol derived from the same precursor. The regulation of bile salt synthesis by two compounds that could alter the precursor pool of cholesterol was studied. After a 24-hr incubation in serum-free medium, the compound 25(OH)cholesterol inhibited the rate of bile salt synthesis compared with control values, possibly by depleting the intracellular free cholesterol pool. Surprisingly, however, progesterone, which inhibits cholesterol esterification and should have expanded this pool, also inhibited bile salt synthesis under those conditions. The effect of these compounds on the level of mRNA for cholesterol 7α-hydroxylase was also determined by Northern-blot analysis. The cholesterol 7α-hydroxylase mRNA was 3.7 kb, similar to that in the rat. The incubation of cells in 25(OH)cholesterol or progesterone, as above, resulted in a decreased level of mRNA. The reduction was proportional to the reduction in bile salt synthesis, suggesting that these compounds act at a pretranslational level. Taken together, these results suggest that our particular subclone of HepG2 cells will be useful for studies of the regulation of bile salt synthesis, but not of transport, by human liver—derived tissue. (Hepatology 1994;20:1522-1531).
The physiological position of the liver in the circulation is not a major determinant of its functional capacity
Authors: Wagenaar Gerry T. M. , Chamuleau Robert A. F. M. , Maas Martinus A. W. , De Bruin Kora , Korfage Hans A. M. , Lamers Wouter H.
Published: March 2007

The zonal patterns of gene expression in the liver of the rat are not affected by alteration of the afferent hepatic blood source. We investigated whether afferent hepatic blood source or flow rate affects the metabolic capacity of the liver. Using microsurgical techniques, we changed the afferent hepatic blood source to solely arterial blood, solely portal blood or solely caval blood. The transhepatic flow rate was four times higher in arterialized than in cavalized livers. Liver function was tested 2 wk after surgery. Three liver functions were tested (elimination of hepatic iminodiacetic acid from the liver and elimination of galactose and ammoniumbicarbonate from the circulation). Our results show that the afferent hepatic blood flow rate rather than the source of the afferent hepatic blood affects the elimination of the substrates tested. We found that at the physiological flow rate of approximately 15 ml/min and beyond, metabolic function does not depend on the flow of the afferent hepatic blood but that at lower flow rates the flow becomes a major determinant of the metabolic function of the liver. We conclude that the position of the liver within the circulation (i.e. between the gastrointestinal tract and the systemic circulation) is apparently not a prerequisite for adequate metabolic activity, at least for the substrates tested, provided that the liver is sufficiently perfused with blood. (Hepatology 1994;20:1532-1540).
Role of polymorphonuclear leukocytes in galactosamine hepatitis: Mechanism of adherence to hepatic endothelial cells
Authors: Komatsu Yutaka , Shiratori Yasushi , Kawase Tateo , Hashimoto Naoaki , Han Katsuken , Shiina Shuichiro , Matsumura Masayuki , Niwa Yasuro , Kato Naoya , Tada Minoru , Ikeda Yusei , Tanaka Mitsugu , Omata Masao
Published: March 2007

To investigate the role of polymorphonuclear leukocytes in galactosamine-induced hepatic injury, we injected rats intraperitoneally with antiserum against rat polymorphonuclear leukocytes to deplete circulating neutrophils, then administered galactosamine plus lipopolysaccharide. Polymorphonuclear leukocytes in the hepatic sinusoids were increased after administration of galactosamine plus lipopolysaccharide, whereas pretreatment with the antiserum decreased the number of circulating leukocytes and reduced the mortality and the severity of hepatic injury. Serum collected 1 hr after galactosamine/lipopolysaccharide treatment enhanced in vitro polymorphonuclear leukocyte adherence to hepatic endothelial cells and induced leukocyte superoxide production. Intercellular adhesion molecule-1 expression on hepatic endothelial cells was also enhanced after stimulation with the serum. Polymorphonuclear leukocyte adhesion was partially inhibited by an antibody against tumor necrosis factor-α but not by superoxide dismutase. These results suggest that polymorphonuclear leukocytes play an important role in galactosamine-induced hepatic injury and that the accumulation and activation of leukocytes, as well as the enhanced expression of adhesion molecules on hepatic endothelial cells, can be induced by biologically active mediators such as tumor necrosis factor-α. In addition, prostaglandins E1 and E2 lessened the enhanced adherence of polymorphonuclear leukocytes and thus contributed to protection against hepatic injury. (Hepatology 1994;20:1548-1556).