bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Effect of Gypenoside on Chronic Liver Injury and Fibrosis Induced by CCl4 in Rats
Authors: Chen Jung-Chou , Tsai Chin-Chuan , Chen Leih-Der , Chen Hing-Ho , Wang Wen-Chuang
Published: November 2003

Gypenoside is a saponins extract derived from the Gynostemma pentaphyllum. The purpose of this study was to evaluate the hepatoprotective and antifibrotic potential of Gypenoside on chronic liver injury induced by CCl 4 for 8 wks. The results indicated that the increase of SGOT, SGPT activities in CCl 4 liver injury were significantly reduced by treatment with Gypenoside. It also elevated the A/G ratio. For the study of anti-fibrotic potential, Gypenoside reduced the collagen content by 33%. These phenomena were confirmed by pathologic observation; thinner bands of liver collagen were found. The results suggest that Gypenoside has hepatoprotective and anti-fibrotic activities.
Effects of Red Ginseng upon Vascular Endothelial Function in Patients with Essential Hypertension
Authors: Sung Jidong , Han Ki-Hoon , Zo Joo-Hee , Park Hwa-Jin , Kim Cheol-Ho , Oh Byung-Hee
Published: November 2003

This study is to estimate the effect of Korean red ginseng on vascular endothelial cell dysfunction in patients with hypertension. Seventeen patients with hypertension who were divided into ginseng-treated (7) and non-treated (10) groups and 10 normotensive subjects were included. To assess the function of the vascular endothelial cell, changes of forearm blood flow to infusion of acetylcholine, sodium nitroprusside and bradykinin in incremental doses were measured by venous occlusion plethysmography. In the ginseng-treated hypertensive group, forearm blood flows at the highest dose of acetylcholine and bradykinin were significantly higher than those of the non-treated hypertensive group and were not different from those of the control group. In the case of sodium nitroprusside infusion, no significant differences were observed between the control, non-treated and treated groups. In conclusion, Korean red ginseng can improve the vascular endothelial dysfunction in patients with hypertension possibly through increasing synthesis of nitric oxide.
Enhanced Expression of Inducible Nitric Oxide Synthase by Juzen-Taiho-To in LPS-Activated RAW264.7 Cells, a Murine Macrophage Cell Line
Authors: Kawamata Hiroshi , Ochiai Hiroshi , Mantani Naoki , Terasawa Katsutoshi
Published: November 2003

We have investigated the effect of Juzen-taiho-to (TJ-48) on inducible NO synthase (iNOS) expression and nitric oxide (NO) production in RAW264.7 cells, a murine macrophage cell line. TJ-48-lipopolysaccharide (LPS) combination induced iNOS mRNA expression earlier, stronger and remained longer that paralleled but with a higher NO production compared to LPS stimulation. TJ-48 itself showed no inducible effect either no NO production or iNOS mRNA expression. This phenomenon could be considered to contribute, at least in part, to the beneficial effects of TJ-48 through the iNOS-mediated activation of biodefense mechanism.
Effects of Berberine on Arylamine N-acetyltransferase Activity and 2-Aminofluorene-DNA Adduct Formation in Human Leukemia Cells
Authors: Chung J. G. , Chen G. W. , Hung C. F. , Lee J. H. , Ho C. C. , Ho H. C. , Chang H. L. , Lin W. C. , Lin J. G.
Published: November 2003

Berberine is an alkaloid occuring in the plant genera Berberis and Coptis. Although berberine had been demonstrated to have antineoplastic function by inhibiting DNA-synthesis in activated lymphocytes, there is no available information to address berberine affects on human leukemia cell N-acetyltransferase (NAT) activity and 2-aminofluorene (AF)-DNA adduct formation. Thus, berberine was tested for inhibition of arylamine NAT activity and AF-DNA adduct formation in human leukemia cells. The NAT activity was measured by a high performance liquid chromatography assaying for the amounts of N-acetyl-2-aminofluorene (AAF) and N-acetyl-p-aminobenzoic acid (N-Ac-PABA) and the remaining AF and p-aminobenzoic acid (PABA). The NAT activity and AF-DNA adduct formation in human leukemia cells were inhibited by berberine in a dose-dependent manner, i.e. the higher the concentration of berberine, the higher the inhibition of NAT activity and AF-DNA adduct. The data also indicate that berberine decreased the apparent values of Km and Vmax from human leukemia cells in both cytosol and intact cells.
Effects of Yukmi, an Herbal Formula, on the Liver of Senescence Accelerated Mice (SAM) Exposed to Oxidative Stress
Authors: Kim Jeong Sang , Na Chang Su , Pak Sok Cheon , Kim Young Gon
Published: November 2003

The effects of Yukmi (Decoction of six plants including rehmannia), an herbal formula, were studied on liver oxidant damage induced by paraquat (PQ) administered intravenously in the senescence accelerated mice (SAM-P/8). The activities of superoxide dismutase (SOD) and catalase as two major antioxidant enzymes and lipid peroxidation levels were determined for six days. Data show that the activities of hepatic SODs and catalase were increased by oral administration of Yukmi extracts following PQ pretreatment. Herbal medicine effectively blocked the PQ-induced effects on liver malondialdehyde (MDA) levels. For the histopathological changes in SAM-P/8 liver, Yukmi extracts inhibited PQ-induced damage to the hepatic mitochondria and their membranes. Data suggest that Yukmi extracts may be useful in protecting against oxidative damage.
Clinical and Pharmacological Studies on Liver Disease Treated with Kampo Herbal Medicine
Authors: Cyong Jong-Chol , Kim Sun-Min , Iijima Koji , Kobayashi Takao , Furuya Minoru
Published: November 2003

Hepatitis C virus (HCV) infection frequently causes chronic hepatitis, which is linked to the development of liver cirrhosis and hepatocellular carcinoma. Most physicians who practice Kampo medicine in Japan have observed that Kampo medicine can be as effective as interferon therapy in the treatment of chronic hepatitis C. In the present study, to evaluate the effect of Kampo medicine on chronic hepatitis C, clinical treatment was assessed in short-term and long-term study, and it was shown that Ninjin-yoei-to (Formula ginseng compositae: TJ-108 was very effective. Therefore, to find the most active herbal component of TJ-108, in the treatment of HCV, Citrus Unshiu Peel, Schisandra Fruit, and Polygala Root, which are specific to TJ-108, were screened using an in vitro HCV infection model. Among the three herbs, Schisandra Fruit was found to be most active. In the next step, Gomisin A, an active component of Schisandra Fruit, was studied using an in vitro model with MOLT-4 cells and an animnal model of immunologically induced acute hepatic failures. It is concluded that the therapeutic effect of TJ-108 on chronic hepatitis C is from the inhibitory effect on HCV infection, and also from the protective effect on immunological hepatopathy of Schisandra Fruit and its lignan component, Gomisin A.
Effect of Combined Citrullus Colocynthis and Rhazya Stricta Use in Najdi Sheep
Authors: Adam S. E. I. , Al-Farhan A. H. , Al-Yahya M. A.
Published: November 2003

The effect of oral administration of 0.25 g/kg/day of Citrullus colocynthis fruits, 0.25 g/kg/day of Rhazya stricta leaves or mixture of the two plants at 0.25 g/kg/day of C. colocynthis fruits plus 0.25 g/kg/day of R. stricta leaves in Najdi sheep was examined. Oral administration of 0.25 g/kg/day of C. colocynthis fruits or 0.25 g/kg/day of R. stricta leaves for 42 days proved not fatal but that of the mixture of the two plants (0.25 g + 0.25 g/kg/day) proved fatal within 26 days with profuse diarrhea, dehydration, loss in condition, ataxia and recumbency, prior to death. These manifestations accompanied by enterohepatonephrotoxicity, gelatinization of the renal and epicardial fat and transudate in serous cavities were correlated with alterations in serum LDH and AST activities and concentrations of total protein, albumin, globulin, bilirubin, cholesterol and urea and hematology.
Chronotherapy in Traditional Chinese Medicine
Authors: Samuels Noah
Published: November 2003

The circadian rhythm of illness has been emphasized for thousands of years in Traditional Chinese Medicine (TCM), using this knowledge to schedule therapies such as acupuncture during appropriate hours of the day. This paper reviews the time periods (two hours segments) that apply to each organ system according to TCM (lungs, large intestine, stomach, heart, kidneys and liver), and elaborates on how recent medical research has found similar relevant biorhythms in these very same organ systems.
Different Frequencies of Electroacupuncture Modified the Cellular Activity of Serotonergic Neurons in Brainstem
Authors: Kwon Young-bae , Kang Myung-soo , Son Sung-sae , Kim Jun-tae , Lee Yon-ho , Han Ho-jae , Lee Jang-hern
Published: November 2003

In this study, we evaluated whether different frequencies of electroacupuncture (EA) modified the activities of serotonergic neurons in the dorsal raphe (DR) and raphe magnus (RMg) using double labeling immunohistochemistry for Fos and serotonin. The results demonstrated that both high and low frequency EA increased the colocalization between Fos and serotonin in the DR, not in RMg as compared with anesthesia control. In addition, high frequency EA more potently increased the serotonergic activity in the DR rather than low frequency EA, suggesting that serotonergic path-way from the DR plays an important role in the high frequency EA analgesia.
Laser Acupuncture for Adolescent Smokers — A Randomized Double-Blind Controlled Trial
Authors: Cai Yiming , Zhao Changxin , Wong Song Ung , Zhang Lei , Lim Seuk Kean
Published: November 2003

A double blind, randomized, placebo-controlled clinical study was conducted to evaluate the efficacy of laser acupuncture treatment in adolescent smokers. Three hundred and thirty adolescent smokers at the Smoking Cessation Clinic of Child Guidance Clinic, Institute of Health, Singapore, were randomly assigned in equal numbers to laser acupuncture treatment and sham acupuncture (control) groups. The proportions of patients with complete smoking cessation after completing treatment for four weeks were 21.9% in the treatment group and 21.4% in the control group. At three months post-treatment, the rates for complete cessation were 24.8% and 26.2%, respectively. Thus, there was no significant difference in the rates of smoking cessation in the treatment and control groups.
Self-assembly of Particle Wires in 2-D Ordered Array
Authors: Masuda Yoshitake , Itoh Minoru , Koumoto Kunihito
Published: November 2003

We developed a novel self-assembly process to fabricate an orderly array of particle wires constructed from a close-packed structure from colloidal solution without preparation of patterned templates. A substrate was immersed into the solution containing particles perpendicular to the liquid surface and the liquid surface was moved downward by evaporation of solution. Particles formed a mono/multi-particle layer and the particle layer was cut by the periodic drop-off of the solution. This process allowed us to fabricate the orderly array of particle wires and to show the high ability of the self-assembly process for fabrication of nano/micro-structures constructed from nano/micro particles or blocks.
Tinzaparin: Considerations for Use in Clinical Practice
Authors: Nutescu Edith A , Shapiro Nancy L , Feinstein Helen , Rivers Christina W
Published: November 2003

OBJECTIVE:

To evaluate the safety and effectiveness of tinzaparin for the prevention and treatment of venous thromboembolism (VTE).

DATA SOURCES:

A MEDLINE and PubMed database search (1980–December 2002) was conducted. Only articles written in English were reviewed.

STUDY SELECTION AND DATA EXTRACTION:

Articles reporting the safety, efficacy, and cost-effectiveness of tinzaparin in humans were evaluated. Emphasis was placed on randomized, controlled trials.

DATA SYNTHESIS:

Tinzaparin sodium is a low-molecular-weight heparin (LMWH) that exerts its anticoagulant effect through inhibition of factors Xa and IIa and release of tissue factor pathway inhibitor from the vascular epithelium. Tinzaparin is indicated for treatment of acute symptomatic deep-vein thrombosis (DVT), with or without pulmonary embolism. Clinical studies suggest that tinzaparin is also effective for VTE prophylaxis, as well as other indications. Once-daily subcutaneous tinzaparin is equally or more effective than intravenous unfractionated heparin (UFH) for prevention and treatment of VTE, at least as safe as UFH for bleeding complications, and requires little or no monitoring. No dose “cap” is required for obese patients, and no initial dosing adjustments are necessary in elderly and/or renally impaired patients, although some monitoring is recommended. The few comparative data available suggest that tinzaparin efficacy may be comparable to that of other LMWHs; more comparative studies are needed. Pharmacoeconomic studies indicate a favorable cost—benefit ratio.

CONCLUSIONS:

Tinzaparin is safe and effective for prevention and treatment of DVT. Consistent once-daily dosing may facilitate self-administration of tinzaparin in the outpatient setting.
Weak measurement invariance with respect to unmeasured variables: An implication of strict factorial invariance
Authors: Lubke Gitta H. , Dolan Conor V. , Kelderman Henk , Mellenbergh Gideon J.
Published: November 2003

Measurement bias refers to systematic differences across subpopulations in the relation between observed test scores and the latent variant underlying the test scores. Comparisons of subpopulations with the same score on the latent variable can be expected to have the same observed test score. Measurement invariance is therefore one of the key issues in psychological testing. It has been established that strict factorial invariance (SFI) with respect to a selection variable V almost certainly implies weak measurement invariance with respect to V: given SFI, means and variances of observed scores do not depend on V. It is shown that this result can be extended. SFI in groups derived by selection on V has implications not only for V but also for potentially biasing variables W, if W and the selection variable V and/or if W and the factor underlying the observed test scores are statistically dependent. Given SFI with respect to V and prior knowledge concerning these dependencies, it is not necessary to measure and model variables W in order to exclude them as potentially biasing variables if the investigation focuses on groups selected on V.
Local influence analysis of structural equation models with continuous and ordinal categorical variables
Authors: Lee Sik‐Yum , Xu Liang
Published: November 2003

This paper proposes a method to assess the local influence of minor perturbations for a structural equation model with continuous and ordinal categorical variables. The key idea is to treat the latent variables as hypothetical missing data and then apply Cook's approach to the conditional expectation of the complete‐data log‐likelihood function in the corresponding EM algorithm for deriving the normal curvature and the conformal normal curvature. Building blocks for achieving the diagnostic measures are computed via observations generated by the Gibbs sampler. It is shown that the proposed methodology is relatively simple to implement, computationally efficient, and feasible for a wide variety of perturbation schemes. Two illustrative real examples are presented.
Three‐mode analysis of multimode covariance matrices
Authors: Kroonenberg Pieter M. , Oort Frans J.
Published: November 2003

Multimode covariance matrices, such as multitrait‐multimethod matrices, contain the covariances of subject scores on variables for different occasions or conditions. This paper presents a comparison of three‐mode component analysis and three‐mode factor analysis applied to such covariance matrices. The differences and similarities between the non‐stochastic and stochastic approaches are demonstrated by two examples, one of which has a longitudinal design. The empirical comparison is facilitated by deriving, as a heuristic device, a statistic based on the maximum likelihood function for three‐mode factor analysis and its associated degrees of freedom for the three‐mode component models. Furthermore, within the present context a case is made for interpreting the core array as second‐order components.
A general class of latent variable models for ordinal manifest variables with covariate effects on the manifest and latent variables
Authors: Moustaki Irini
Published: November 2003

Previous work on a general class of multidimensional latent variable models for analysing ordinal manifest variables is extended here to allow for direct covariate effects on the manifest ordinal variables and covariate effects on the latent variables. A full maximum likelihood estimation method is used to estimate all the model parameters simultaneously. Goodness‐of‐fit statistics and standard errors are discussed. Two examples from the 1996 British Social Attitudes Survey are used to illustrate the methodology.
The relationship between shame, eating disorders and disclosure in treatment
Authors: Swan Sarah , Andrews Bernice
Published: November 2003

Background: This study considered shame in 68 women who had received treatment for eating disorders (EDs) compared to 72 non‐clinical controls, and shame in relation to disclosure in treatment.

Method: All participants completed questionnaires on ED and depressive symptoms, and bodily, behavioural and characterological shame and shame around eating. ED women also answered questions on disclosure in treatment.

Results: The ED group scored significantly higher than controls on all shame areas when depression was controlled. ED women who were currently symptomatic and those who had recovered scored higher than controls on bodily and characterological shame and shame around eating. Non‐disclosure in treatment was reported by 42% of the ED group and was associated with higher shame in all areas except bodily shame.

Conclusions: The study is the first to show a relationship between shame and ED in a clinical sample. It supports existing evidence regarding the importance of bodily shame in women with EDs, and extends the literature in terms of the importance of other shame aspects for ED symptomatology and disclosure. Implications for treatment are discussed.
The assessment of food‐related problems in individuals with Prader‐Willi syndrome
Authors: Russell Helen , Oliver Chris
Published: November 2003

Objectives: The objective of this study was to develop an informant‐based questionnaire to assess food‐related problems in people with Prader‐Willi syndrome and to conduct an examination of psychometric properties.

Design: Following a content analysis of informant interview responses a 16‐item questionnaire, the Food Related Problem Questionnaire (FRPQ), with three subscales (preoccupation with food, impairment of satiety and other food‐related ‘challenging’ behaviour) was developed. Test‐retest and inter‐rater reliability, concurrent and criterion validity and internal consistency were examined.

Results: Total score test‐retest and inter‐rater reliability coefficients were both .86. Subscale test‐retest and inter‐rater reliability are acceptable for the subscales (range .67 to .85). Total scores on the FRPQ and all subscale scores and differentiated between a group of individuals with Prader‐Willi syndrome and a comparison group (p<.001 in all cases). For relevant items of the FRPQ significant positive correlations with items on the Checklist of Challenging Behaviour were achieved. Internal consistency for the total scale was good (Cronbach's Alpha = .87).

Conclusions: The FRPQ has sufficiently robust psychometric properties for use in future research and clinical practice to appraise the food‐related problems often seen in individuals with Prader‐Willi syndrome.
Test‐retest reliability, practice effects and reliable change indices for the recognition memory test
Authors: Bird Chris M. , Papadopoulou Kyriaki , Ricciardelli Paola , Rossor Martin N. , Cipolotti Lisa
Published: November 2003

Objectives: The Recognition Memory Test (RMT) is widely used; however, important characteristics such as reliability and stability over time were largely unknown. In this study, we document for the first time test‐retest reliabilities, practice effects, and Reliable Change (RC) indices for this test.

Design: A sample of 206 normal adults (aged 40‐70) were administered twice either the same version or two different versions of the RMT, with a 1‐month interval between assessments. The normal sample was split into two groups; a young (aged 40‐54) and an old (55‐70) group.

Results: Test‐retest reliabilities were modest when using either the same versions or different versions. Practice effects were abolished when different versions of the RMT were used. In contrast, practice effects were clearly present on the same version of the non‐verbal subtest for both control groups. However, practice effects were present on the same versions of the verbal subtest only in the old group. RC indices were rather large when using the same or different versions.

Conclusion: Although modest, the test‐retest reliability of the RMT is no worse than those reliabilities reported for other commonly used recall memory tests. Thus, the inherent clinical advantages of using a recognition paradigm make its use desirable. Usage of different versions of the RMT enables us to avoid practice effects. However, the RC indices indicate that large changes in scores are needed to detect a significant improvement or decline in an individual's performance.
The long‐term psychological impact of Bloody Sunday on families of the victims as measured by The Revised Impact of Event Scale
Authors: Shevlin Mark , McGuigan Karen
Published: November 2003

Objectives: In 1972, 13 civil rights marchers were killed in Londonderry, Northern Ireland, on what is known as Bloody Sunday. This study aimed to assess the psychological impact of this event on the families of victims as measured by the Revised Impact of Event Scale.

Design: Cross‐sectional self‐report based study.

Methods: The Impact of Event Scale—Revised was administered to 72 members of the families (immediate family, children of immediate family, cousins, and second cousins) of those killed on Bloody Sunday.

Results: High levels of intrusion, avoidance, and hyperarousal were found. In addition, significant group differences were found. Those family members closest to the victims reported the highest levels of psychological distress.

Conclusion: The findings were discussed within the transgenerational trauma context.
Detection of intracellular macromolecule behavior under strong magnetic fields by linearly polarized light
Authors: Iwasaka M. , Ueno S.
Published: November 2003

Strong static magnetic fields on the order of 10 T have a diamagnetic force on cell components and generate a clear alignment of a smooth muscle cell assembly, parallel to the direction of the magnetic fields within an exposure period of 3 days. This work shows the effects of diamagnetic torque forces on cell component motion. Linearly polarized light was utilized to detect the displacement of intracellular macromolecules. The polarized light passed through a mass of cells in a magnetic field, and transmission of the light increased and reached a plateau 2 h after the beginning of magnetic field exposure at 14 T. However, no distinct change was observed in transmission of the light under zero magnetic field exposure. The change in polarized light intensity through the lamellar cell assembly under magnetic fields corresponds to behavioral changes in cell components. It was speculated that intracellular macromolecules rotated and showed a displacement due to diamagnetic torque forces during 2–3 h of magnetic field exposure at 14 T. Bioelectromagnetics 24:564–570, 2003. © 2003 Wiley‐Liss, Inc.
Effect of 10 kV, 30 μT, 60 Hz electric and magnetic fields on milk production and feed intake in nonpregnant dairy cattle
Authors: Burchard J.F. , Monardes H. , Nguyen D.H.
Published: November 2003

Milk production is the main agricultural income in the province of Québec, and the electrical distribution network traverses the rural dairy production region. This study evaluates the hypothesis that electric and magnetic fields may affect dairy production. Sixteen multiparous nonpregnant lactating Holstein cows (weighing 662 ± 65 kg and with 150.4 ± 40 days of lactation) were confined to wooden metabolic crates during the experiment with a 12:12 h light:dark cycle. The cows were divided into two replicates of eight cows each and exposed to a vertical EF of 10 kV/m and an uniform horizontal MF of 30 μT at 60 Hz. Replicate one was exposed for three periods. Each period was represented by an estrous cycle ranging from 24 to 27 days. During the first period, the electric and magnetic fields (E&MF) were off; during the second period they were on; and during the final period, they were off. The second replicate was exposed for three periods also, but the exposure protocol was reversed (first period, on; second period, off; last period, on). Exposure to E&MF (on) resulted in an average decrease of 4.97, 13.78, and 16.39% in milk yield, fat corrected milk yield, and milk fat, respectively; and an increase of 4.75% in dry matter intake. Bioelectromagnetics 24:557–563, 2003. © 2003 Wiley‐Liss, Inc.
Effect of 50 Hz, 0.2 mT magnetic fields on RBC properties and heart functions of albino rats
Authors: Ali Fadel M. , S. Mohamed Wael , Mohamed Mostafa R.
Published: November 2003

In this work the effect of sinusoidal 50 Hz, 0.2 mT magnetic fields on the red blood cells (RBCs) and heart functions of Albino rats were investigated. Twenty‐four male Albino rats were equally divided into four groups, A, B, C, and D. Animals from groups B were continuously exposed to the magnetic field for 15 days; and groups C and D, for 30 days. Group A was used as control. Animals from group D were kept after exposure to the magnetic field for a period of 45 days for delayed effect studies. The osmotic fragility and shape of RBCs' membrane and hemoglobin (Hb) structure tests were carried out for all groups. The dielectric relaxation of Hb molecules was measured in the frequency range of 0.1–10 MHz and the dielectric increment (Δε), relaxation time (τ), molecular radius (r), and Cole‐Cole parameter (α) were calculated for all groups. The ECG was measured for all animals before and after exposure to the magnetic field. The results indicated that exposure of the animals to 50 Hz, 0.2 mT magnetic fields resulted in the decrease of RBCs membrane elasticity and permeability and changes in the molecular structure of Hb. The ECG of the exposed animals was considerably altered. The data also indicated that there was no sign of repair in the newly generated RBCs structure and the ECG after removing the animals from the magnetic field, which indicates that the blood generating system was severely injured. The injuries in the heart of the animals were attributed to the loss of some physiological functions of the RBCs as a result of exposures of the rats to the magnetic field. Bioelectromagnetics 24:535–545, 2003. © 2003 Wiley‐Liss, Inc.
Waveform magnetic field survey in Russian DC and Swiss AC powered trains: A basis for biologically relevant exposure assessment
Authors: Ptitsyna N.G. , Kopytenko Y.A. , Villoresi G. , Pfluger D.H. , Ismaguilov V. , Iucci N. , Kopytenko E.A. , Zaitzev D.B. , Voronov P.M. , Tyasto M.I.
Published: November 2003

Recent epidemiological studies suggest a link between transport magnetic fields (MF) and certain adverse health effects. We performed measurements in workplaces of engineers on Russian DC and Swiss AC powered (16.67 Hz) electric trains using a computer based waveform capture system with a 200 Hz sampling rate. MF in DC and AC trains show complex combinations of static and varying components. The most probable levels of quasistatic MF (0.001–0.03 Hz) were in the range 40 μT. Maximum levels of 120 μT were found in DC powered locomotives. These levels are much higher than the geomagnetic field at the site of measurements. MF encountered both in DC and AC powered rail systems showed irregular temporal variability in frequency composition and amplitude characteristics across the whole frequency range studied (0–50 Hz); however, more than 90% of the magnetic field power was concentrated in frequencies ≤16.67 Hz. In AC locomotives, such as the most popular engine Re 4/4 II, the major energy falls around the fundamental frequency 16.67 Hz, with an average magnetic field intensity of about 44 μT; moreover, a significant contribution (about 15%) is due to components below the fundamental frequency. In Russian DC powered trains amplitudes of field variations sharply decrease from static to ∼3–4 Hz fields; for higher frequencies a tendency of slow decrease is observed up to 50 Hz. For frequencies higher than 1 Hz average amplitudes of magnetic field variations are less than 1 μT; maximum levels reach tens of microtesla. At frequencies lower than 15 Hz, the average magnetic field generated by Swiss AC powered locomotives was ∼10 times greater than fields observed in Russian DC powered trains. Bioelectromagnetics 24:546–556, 2003. © 2003 Wiley‐Liss, Inc.
GSM modulated radiofrequency radiation does not affect 6‐sulfatoxymelatonin excretion of rats
Authors: Bakos József , Kubinyi Györgyi , Sinay Hanna , Thuróczy György
Published: November 2003

In this study, the effect of exposure to 900 and 1800 MHz GSM‐like radiofrequency radiation upon the urinary 6‐sulfatoxymelatonin (6SM) excretion of adult male Wistar rats was studied. Seventy‐two rats were used in six independent experiments, three of which were done with 900 MHz and the other three with 1800 MHz. The exposures were performed in a gigahertz transverse electromagnetic mode (GTEM) cell. The power densities of radiation were 100 and 20 μW/cm2 at 900 and 1800 MHz frequency, respectively. The carrier frequency was modulated with 218 Hz, as in the GSM signal. The animals were exposed for 2 h between 8:00 AM and noon daily during the 14 day exposure period. The urine of rats was collected from 12:00 AM to 8:00 AM, collecting from exposed and control animal groups on alternate days. The urinary 6SM concentration was measured by 125I radioimmunoassay and was referred to creatinine. The combined results of three experiments done with the same frequency were statistically analyzed. Statistically significant changes in the 6SM excretion of exposed rats (n = 18) compared to control group (n = 18) were not found either at 900 or 1800 MHz. Bioelectromagnetics 24:531–534, 2003. © 2003 Wiley‐Liss, Inc.
TGFβ directs gene expression of activated microglia to an anti‐inflammatory phenotype strongly focusing on chemokine genes and cell migratory genes
Authors: Paglinawan Rey , Malipiero Ursula , Schlapbach Ralph , Frei Karl , Reith Walter , Fontana Adriano
Published: November 2003

In experimental autoimmune encephalomyelitis, the acute phase of the disease is produced by T‐helper lymphocyte type 1 (TH1), which produces mainly TNFα and IFNγ. Recovery from the disease is mediated by T‐helper lymphocyte types 2 and 3 (TH2/TH3), which, among other cytokines, produce transforming growth factor β (TGFβ). To address the influence of TGFβ on TH1‐induced gene expression, microarray technology was used on murine primary microglial cells stimulated with IFNγ and TNFα in the absence or presence of TGFβ. The resulting data from an investigation of up to 5,500 genes provided the notion that TGFβ prevents the induction of a proinflammatory gene program within microglia exposed to a TH1 milieu. TH1 cytokines upregulated 175 genes comprising cytokine, chemokine, and genes involved in host response to infection and the TNFα/IFNγ intracellular signaling pathway. It is observed that TGFβ inhibits expression of 25% of the TNFα/IFNγ‐induced genes and a further 66 TNFα/IFNγ‐independent genes. The focus of TGFβ inhibition is observed to be directed in genes involved in chemotaxis (IL‐15, CXCL1, CXCL2, CCL3, CCL4, CCL5, CCL9), chemokine receptors (CCR5, CCR9), LIF receptor, and FPR2, and on genes mediating cell migration (MMP9, MMP13, MacMARCKS, endothelin receptor B, Ena/VASP, Gas7), apoptosis (FAS, TNF, TNF receptor, caspase‐1 and ‐11), and host response to infection (toll‐like receptor 6, Mx‐1, and MARCO). Taken collectively, the data strongly suggest that one of the main effects of TGFβ is to impair cell entry into the CNS and to hinder migration of microglia in the CNS parenchyma. © 2003 Wiley‐Liss, Inc.
Expression of the B7‐related molecule ICOSL by human glioma cells in vitro and in vivo
Authors: Schreiner Bettina , Wischhusen Jörg , Mitsdoerffer Meike , Schneider Dagmar , Bornemann Antje , Melms Arthur , Tolosa Eva , Weller Michael , Wiendl Heinz
Published: November 2003

Human glioblastoma is a highly lethal tumor known for its capability of interfering with effective antitumor immune responses. Costimulatory signals are of critical relevance in both the inductive and effector phases of immune responses. Inducible costimulator‐ligand (ICOSL), a member of the B7 family of costimulatory molecules related to CD80/CD86, regulates CD4 as well as CD8 T‐cell responses via interaction with its receptor, ICOS, on activated T cells. We report the expression of ICOSL by glioma cells in vitro and in vivo. In contrast to CD80 (B7.1) and CD86 (B7.2), ICOSL protein and mRNA was expressed in 7 of 12 glioma cell lines. ICOSL expression is upregulated by the inflammatory cytokine, tumor necrosis factor‐α (TNF‐α), whereas interferon‐γ (IFN‐γ) has no such effect. Further, immunohistochemical analysis of human brain tumors demonstrates the expression of ICOSL in three of four tissue samples. ICOSL expression is functional in that a neutralizing ICOSL antibody (HIL‐131) reduces Th1 and Th2 cytokine levels in cocultures of peripheral blood lymphocytes or T‐cell subsets (CD4 and CD8) with glioma cells. However, ICOSL gene transfer into glioma cells does not alter their immunogenicity under primary or secondary alloreactive coculture assays. © 2003 Wiley‐Liss, Inc.
Proteomic profiling of primary retinal Müller glia cells reveals a shift in expression patterns upon adaptation to in vitro conditions
Authors: Hauck Stefanie M. , Suppmann Sabine , Ueffing Marius
Published: November 2003

Cultured primary retinal Müller glia cells (RMG), a glia cell spanning the entire neuroretina, have recently gained increased attention, especially with respect to their presumed in vivo role in supporting photoreceptor function and survival. Cultured RMG cells, however, are at risk to lose much of their in vivo features. To determine the conditions of isolated primary RMG cells best corresponding with their physiological role in the intact retina, we profiled the respective proteomes of RMG freshly isolated from intact pig eye, as well as from cultured material at different timepoints. Protein samples were separated by high‐resolution two‐dimensional electrophoresis (2‐DE), and isolated proteins were identified by matrix‐assisted laser desorption ionization time‐of‐ flight (MALDI‐TOF) peptide mass fingerprint. Compared with freshly isolated RMG, the in vitro protein expression patterns remain relatively stable for the first 3 days in culture but change dramatically thereafter. Proteins involved in specific RMG physiological functions, such as glycolysis, transmitter recycling, CO2 siphoning, visual pigment cycle, and detoxification, are either downregulated or absent. In contrast, cytoskeletal proteins, as well as proteins involved in motility and in proliferation, are upregulated during culture. In the present report, we show for the first time, on a systematic level, that profound changes in the RMG proteome reflect transdifferentiation from a multifunctional, highly differentiated glial cell to a dedifferentiated fibroblast‐like phenotype in culture. © 2003 Wiley‐Liss, Inc.
Selective expression of Gi/o‐coupled ATP receptor P2Y12 in microglia in rat brain
Authors: Sasaki Yo , Hoshi Masato , Akazawa Chihiro , Nakamura Yasuko , Tsuzuki Hayami , Inoue Kazuhide , Kohsaka Shinichi
Published: November 2003

Extracellular nucleotides, including ATP, have been demonstrated to transmit important physiological signals in the brain through either G‐protein‐coupled P2Y receptors or P2X receptors, which are ligand‐gated ion channels. In this study, we performed a detailed analysis of the expression of the Gi/o‐coupled receptor P2Y12 in the brain. Northern blot analysis demonstrated that P2Y12 is expressed predominantly in the brain, and to a lesser extent in the spleen. The cellular localization of P2Y12 was investigated by in situ hybridization, and P2Y12 mRNA was detected in small cells distributed throughout the brain, including the hippocampus. Expression of P2Y12 was also observed in naive and axotomized facial nuclei, and the number of P2Y12‐expressing cells increased following facial nerve axotomy. Selective expression of P2Y12 mRNA in microglia was confirmed by double‐label in situ hybridization and immunohistochemistry with antibodies against NeuN and Iba1 as an immunohistochemical marker for neurons and microglia, respectively. Hardly any P2Y12 mRNA was detected in macrophages obtained from the spleen and abdominal cavity, which share many surface molecules with microglia. © 2003 Wiley‐Liss, Inc.
Extracellular phospholipase A2 inhibitors suppress central nervous system inflammation
Authors: Pinto Florence , Brenner Talma , Dan Phyllis , Krimsky Miron , Yedgar Saul
Published: November 2003

Phospholipase A2 (PLA2) plays a key role in the production of proinflammatory mediators, namely the arachidonic acid‐derived eicosanoids, lysophospholipids, and platelet‐activating factor, and indirectly influences the generation of cytokines, nitric oxide (NO), and free radicals. Accordingly, regulation of its activity is important in the treatment of inflammation. Since the main site of PLA2 action in inflammatory processes is the cell membrane, we synthesized extracellular PLA2 inhibitors (ExPLIs) composed of N‐derivatized phosphatidyl‐ethanolamine linked to polymeric carriers. These membrane‐anchored lipid conjugates do not penetrate the cell and interfere with vital phospholipid metabolism or cell viability. The ExPLIs markedly inhibited central nervous system inflammation. This was reflected by the suppressed production and secretion of lipopolysaccharide‐induced sPLA2, prostaglandin E2, and NO by glial cells and by the amelioration of experimental autoimmune encephalomyelitis in rats and mice. © 2003 Wiley‐Liss, Inc.
Manipulation of olfactory ensheathing cell signaling mechanisms
Authors: Hayat Shaista , Thomas Anu , Afshar Farid , Sonigra Rakesh , Wigley Caroline B.
Published: November 2003

Pretreatment of olfactory ensheathing cells (OECs) with Pertussis toxin increased the number of subsequently cocultured adult retinal ganglion cells (RGCs) regrowing neurites without affecting neuronal survival. Pertussis toxin (PTx) inactivated an OEC Gi/o protein as pretreating OECs with the PTx B‐oligomer subunit had no effect on RGC neurite regrowth. However, the B‐oligomer was responsible for decreasing the marked orientation of neurite regrowth on the OEC substrate. Simultaneous incubation of OECs with PTx and a depolarizing concentration of KCl abolished the increase in neurite regrowth from cocultured RGCs, but exposure to a depolarizing KCl concentration after OECs had been PTx‐treated had no effect. Our evidence supports the hypothesis that G‐protein‐regulated calcium signaling plays a significant role in OEC support for CNS axonal regeneration. © 2003 Wiley‐Liss, Inc.
Multifaceted roles of TNF‐α in myoblast destruction: A multitude of signal transduction pathways
Authors: Stewart C.E.H. , Newcomb P.V. , Holly J.M.P.
Published: November 2003

In catabolic conditions, such as cancer cachexia, a balance favouring a cytokine environment culminates in muscle destruction. Utilising an in vitro model to mimic muscle wasting, we elucidate here the multifaceted roles that one such cytokine, TNF‐α, invokes in the degeneration process. Treatment of C2 skeletal myoblasts with TNF‐α not only suppresses morphological and biochemical differentiation, but following an initial wave of proliferation, and of survival (24 h), induces apoptosis. Investigating the mechanisms underlying these diverse actions of TNF‐α, we demonstrate that cell replication is dependent on rapid and sustained activation of MAP kinase. Map kinase is not, however, central to the death process, which is associated with a progressive rise in caspase‐8 activity, and is accompanied by sustained activation of JNK1 and transient activation of JNK2. Caspase inhibition caused a dose responsive reduction in cell death, while inhibition of the JNKs caused a significant increase in apoptosis. We further report that PI3 kinase is not involved in conferring early protection against TNF‐α‐induced death. By contrast, inhibition of NF‐κB in the presence of TNF‐α culminates in increased cell cycle progression, decreased gadd45β expression and significant and precociously increased cell death, when compared with TNF‐α alone. Our results begin to characterise the mechanisms underlying the acute mitogenic and anti‐apoptotic roles of TNF‐α, which appear to be defined by a balance between MAP kinase, Jun kinase (JNK), NF‐κB and gadd45β. They establish that inhibition of any one of these molecules, as may occur following caspase activation, could eliminate vital stem cells required for skeletal muscle regeneration during chronic catabolic conditions. J. Cell. Physiol. 198: 237–247, 2004© 2003 Wiley‐Liss, Inc.
Transcriptional activation of the type I collagen genes COL1A1 and COL1A2 in fibroblasts by interleukin‐4: Analysis of the functional collagen promoter sequences
Authors: Büttner Cordula , Skupin Annett , Rieber Ernst Peter
Published: November 2003

Pneumonitis followed by lung fibrosis is a frequent complication of radiation therapy of chest tumors. A hallmark of these fibrotic lesions is the excessive production and accumulation of extracellular matrix proteins such as type I collagen. In addition to TGF‐β1, IL‐4 has been recognized as a potent inducer of collagen gene synthesis in fibroblasts. In this study, we analyzed the regulation of the α1(I) procollagen (COL1A1) promoter and the α2(I) procollagen (COL1A2) promoter by IL‐4 in normal human lung fibroblasts. We provide evidence that the IL‐4‐induced transcriptional activator STAT6 binds to various sequences within the COL1A1 and COL1A2 promoter. The regulatory function of these regions was tested by reporter gene analysis using 5′ deletions of the COL1A1 and COL1A2 promoter fused to the luciferase gene. Interleukin‐4 treatment of human fibroblasts transiently transfected with COL1A1 promoter deletion constructs resulted in luciferase activity exceeding that of untreated fibroblasts by 25%, while luciferase activity driven by the COL1A2 promoter was enhanced by about 70% upon IL‐4 treatment. A combined action of SP1, NFκB, and STAT6 essentially contributes to the IL‐4 mediated COL1A2 gene activation. An AP2 site adjacent to the reverse orientated STAT6 consensus motif TTC N3/4 GCT is located within 205 bases from the transcription start site and seems to support the moderate IL‐4‐induced COL1A1 gene activation. Interferon‐γ downregulation of transcription is mainly seen with the COL1A1 promoter. J. Cell. Physiol. 198: 248–258, 2004© 2003 Wiley‐Liss, Inc.
Inhibition of estrogen receptor alpha expression and function in MCF‐7 cells by kaempferol
Authors: Hung Huynh
Published: November 2003

Estrogens are mitogenic for estrogen receptor (ER)‐positive breast cancer cells. Current treatment of ER‐positive breast tumors is directed towards interruption of estrogen activity. We report that treatment of ER‐positive breast cancer cells with kaempferol resulted in a time‐ and dose‐dependent decrease in cell number. The concentration required to produce 50% growth inhibition at 48 h was approximately 35.0 and 70.0 μM for ER‐positive and ER‐negative breast cancer cells, respectively. For MCF‐7 cells, a reduction in the ER‐α mRNA equivalent to 50, 12, 10% of controls was observed 24 h after treatment with 17.5, 35.0, and 70.0 μM of kaempferol, respectively. Concomitantly, these treatments led to a 58, 80, and 85% decrease in ER‐α protein. The inhibitory effect of kaempferol on ER‐α levels was seen as early as 6 h post‐treatment. Kaempferol treatment also led in a dose‐dependent decrease in the expression of progesterone receptor (PgR), cyclin D1, and insulin receptor substrate 1 (IRS‐1). Immunocytochemical study revealed that ER‐α protein in kaempferol‐treated MCF‐7 cells formed an aggregation in the nuclei. Kaempferol also induced degradation of ER‐α by a different pathway than that were observed for the antiestrogen ICI 182,780 and estradiol. Estradiol‐induced MCF‐7 cell proliferation and expression of the estrogen‐responsive‐element‐reporter gene activity were abolished in cells co‐treated with kaempferol. These findings suggest that modulation of ER‐α expression and function by kaempferol may be, in part, responsible for its anti‐proliferative effects seen in in vitro. J. Cell. Physiol. 198: 197–208, 2004© 2003 Wiley‐Liss, Inc.
Geldanamycin, a heat shock protein 90‐binding agent, disrupts Stat5 activation in IL‐2‐stimulated cells
Authors: Xu Weijing , Yu Furong , Yan Mingda , Lu Linrong , Zou Weiguo , Sun Lanying , Zheng Zhongcheng , Liu Xinyuan
Published: November 2003

The 90‐kDa heat shock protein (Hsp90) is the most abundant molecular chaperone in eukaryotic cells. Hsp90 plays a critical role in regulating signal transduction pathways that control cell proliferation since its chaperone function is restricted to a subset of proteins including some signal molecules. Improper function of these proteins can be induced by an anti‐tumor agent geldanamycin (GA) which is the specific inhibitor of Hsp90. In this study, it was demonstrated that GA interferes with IL‐2‐stimulated proliferation of murine CTLL‐2 cells. As to the signaling mechanisms underlying this inhibitory effect, we discovered GA disrupts the IL‐2‐stimulated activation and phosphorylation of the transcription factor Stat5, indicating the proper function of Hsp90 is indispensable for Stat5 activation. This conclusion is validated by the observation that Hsp90 interacts with Stat5 in the immunoprecipitation assay and GA interrupts their interaction. Furthermore, by constructing deletion mutants, we identified the c‐terminal half of Stat5 coiled‐coil region is responsible for binding with Hsp90. J. Cell. Physiol. 198: 188–196, 2004© 2003 Wiley‐Liss, Inc.