bluuebunny/crossref_metadata_2025 huggingface dataset:
Unemployment Insurance and Experience Rating in a Simple Model of Involuntary Unemployment
Authors: Alvi Eskander
Published: November 2009

Standard results in the area of unemployment insurance suggest that experience rating is beneficial because it confronts firms with layoff costs and reduces unem ployment. This article presents a different perspective, suggesting that experience rating may increase involuntary unemployment. A simple model that combines elements of efficiency wage and insider-outsider hypotheses is used to address the issues. Results show that experience rating causes significant wage and unemploy ment effects. Thus, standard conclusions in the experience-rating literature may not easily carry over to models of involuntary unemployment. From a policy perspective, this article suggests that costs and benefits of experience rating should be carefully evaluated, especially when unemployment is involuntary.
When Do Small Countries Win Tax Wars?
Authors: Eggert Wolfgang , Haufler Andreas
Published: November 2009

This article analyzes the conditions under which the smaller of two otherwise iden- tical countries prefers the noncooperative Nash equilibrium to a situation of fully harmonized tax rates. A standard two-country model of capital tax competition is extended by allowing for transaction costs, additional countries, and additional tax instruments The effects of introducing either mobility costs or a wage tax instru ment are theoretically ambiguous because they lower both the costs and the benefits of noncooperation from the perspective of the small country. Numerical simulations indicate, however, that for a wide range of parameter values, all model extensions considered reduce the possibility that the small country gains from tax competition.
Tax Evasion By Misinforming Withholding Agents
Authors: Yaniv Gideon
Published: November 2009

This article inquires into a wage earner's decision to evade taxes by splitting his or Abstract her work efforts between several jobs while misinforming his or her employers regarding employment elsewhere. Under exact or approximate withholding by progres sive marginal rates, this behavior, accompanied by the failure to file a tax return, results in the application of lower tax brackets to earnings. This article characterizes the properties of the worker's effort allocation problem under progressive withhold ing, showing that exact withholding, considered to be more costly to administer than approximate withholding, might also be, contrary to common belief, equally and even more evadable than the latter.
Tax Overwithholding as a Response To Uncertainty
Authors: Highfill Jannett , Thorson Douglas , Weber William V.
Published: November 2009

This article analyzes a basic timing problem faced by taxpayers—they must choose their levels of withholding and/or estimated tax payments before knowing exactly what their incomes and deductibles will be. Thus, the laws on withholding impose a compliance cost on taxpayers because they must pay a government-imposed penalty when they underwithhold and they must, in essence, give the government an interest-free loan when they overwithhold. The model in this article shows that when the penalty for underwithholding exceeds the opportunity cost of overwithholding, it is optimal for taxpayers to overwithhold more often than they underwithhold. Furthermore, this model is shown to substantially explam the observed withholding patterns for the U.S. individual income tax.
Public Sector Crowding Out of Private Provision of Public Goods: the Influence of Differences in Production Costs
Authors: Coates Dennis
Published: November 2009

This article introduces differentials in the production costs in the public and private sectors to models of public and private provision of public goods. The result of this exercise is to show that imperfect crowding out of private provision by public provision may occur even when the contributors are perfectly altruistic. Moreover, contrary to Andreoni's assertion that impure altruism is sufficient for less than perfect crowding out, the results of this analysis demonstrate that perfect crowding out is possible even when altruism is impure. Finally, the analysis shows that taxation of nondonors or taxation in excess of voluntary contributions is not sufficient to ensure that the public provision increases the total supply of the public good.
Corporate Income Taxation and Signaling
Authors: Kwang Soo Cheong
Published: November 2009

A signaling model is developed to investigate the consequences of corporate income taxation in the presence of adverse selection in the equity market. The model obtains a unique, informationally constrained efficient equilibrium in which a better quality firm retains more inside equity, and, as in the complete information case, only profitable firms are supported The corporate income tax affects signaling costs and the profitability of projects. Numerical experiments with exponential utility functions find that the inside equity position of a better quality firm increases as the corporate income tax rate rises. This reaction is, however, insensitive to the tax rate change due to the risk sharing with the government, which leads to the interesting result that the corporate income tax only incurs a lower welfare cost than the lump sum tax with the same tax revenue.
Using Survey Data To Test for Ricardian Equivalence
Authors: Allers Maarten , De Haan Jakob , De Kam Flip
Published: November 2009

Drawing on nationwide and representative survey data for the Netherlands, this article tests, first, to what degree economic subjects are aware of the level of both government debt and deficits, and, second, examines whether fiscal policy relates to individual saving decisions. The results presented suggest that one of the central assumptions of the Ricardian equivalence hypothesis must be refuted: most individu als have little knowledge of the government's indebtedness. Furthermore, their saving behavior appears not to be influenced by the fiscal policy stance. The authors show that individual responses vary with age, education, income, and employment status, but not with having offspring.
The Tax Incidence of Casino Gaming in Mississippi
Authors: Rivenbark William C.
Published: November 2009

In 1990, the Mississippi legislature passed the Gaming Control Act, legalizing dockside casino gaming for the state of Mississippi. During FYs 1993, 1994, and 1995, the state collected a combined total of $256.9 million in gamingfees and taxes from the casino industry. The $128.6 million received in FY 1995 equated to 5.04% of the state's generalfund revenue. This study determines the tax incidence of casino gaming in Mississippi for the eight casino counties and the remaining noncasino counties, taking into account accessibility to casino play. During April 23, 1995, and April 27, 1995, a telephone survey produced 397 and 410 usable responses from casino counties and noncasino counties, respectively. Using log-linear regression analysis, it was found that although the tax incidence was regressive for both populations, a more regressive tax ensued from counties with casino gaming. This research provides additional evidence to the theory that once readily available, the poor become more attracted to gaming endeavors.
An Incentive-Compatibility Approach To the Problem of Monitoring a Bureau
Authors: Claar Victor V.
Published: November 2009

An incentive-compatibility framework for regulating a monopolist with unknown costs is applied to the sponsor's problem of monitoring a bureau. Following Mueller, the bureau does not make take-it-or-leave-it budget proposals to the sponsor. Rather, the bureau must announce a marginal cost per unit of output to the sponsor. Given that report, the sponsor chooses a price that it will pay to the bureau for each unit of output, and the sponsor chooses the level of output as well. The analysis reveals the price per unit of output that the sponsor must pay to the bureau to maximize social welfare.
Ingested IFN-α has biological effects in humans with relapsing-remitting multiple sclerosis
Authors: Brod Staley A , Kerman Ronald H , Nelson Laura D , Marshall Gailen D , Henninger Evelyn M , Khan Mohammed , Jin Rui , Wolinsky Jerry S
Published: November 2009

Parenterally administered human recombinant type I interferons (hrIFN) in relapsing-remitting multiple sclerosis (RRMS) decrease relapses and spontaneous in vitro IFN-γ production, reduce clinical progression, and decrease magnetic resonance imaging (MRI)-defined disease activity and lesions. Parenterally administered type I IFN use is limited by clinical and chemical toxicities, and the induction of antibodies that abrogate their activity in vivo correlated with the loss of clinical benefit. Therefore, we determined whether ingested IFN-α was non-toxic and had biological effects in humans. ingested hrIFN-α showed no toxicity in normal volunteers or patients with RRMS at doses ranging from 300 to 100 000 units. In subjects with RRMS, a significant decrease in Con A-mediated proliferation and serum soluble intercellular adhesion molecule-I (sICAM-I), a surrogate measure for disease activity in MS, was found after ingesting 10 000 and 30 000 units IFN-α The RRMS subjects also showed decreased IL-2 secretion after ingesting 10 000 units IFN-α, and decreased IFN-γ, TGF-β and IL-10 production after ingesting 30 000 units IFN-α. The decreased secretion of IFN-γ and IL-2 by ingested IFN-α suggests that oral IFN-α may cause a functional inhibition of Th I-like T helper cells in RRMS, a potential site of intervention at the level of effector T cells in MS. Our studies support the oral use of human IFN-α as a biological response modifier in humans.
Positron emission tomography, magnetic resonance imaging and proton NMR spectroscopy of white matter in multiple sclerosis
Authors: Schiepers Christiaan , Van Hecke Paul , Vandenberghe Rik , Van Oostende Sylvie , Dupont Patrick , Demaerel Philippe , Bormans Guy , Carton Herwig
Published: November 2009

Objective: To assess characteristics of MS lesions and normal appearing white matter (NAWM) with various imaging modalities. Glucose metabolism was investigated with FDG - PET, metabolite concentration with proton NMR spectroscopy, and lesion detection with routine brain MRI. Methods: Thirteen patients were studied in a stable phase of their disease, and two during an acute episode. Nine healthy volunteers served as controls. Results: Three patients had a normal brain MRI, 12 had typical lesions. MR images were registered to the PET planes. Lesions and contra-lateral control areas were analyzed, 10/15 lesions showed relative hyper-metabolism and 2 hypo-metabolism. NAA concentration was significantly decreased in both lesions and NAWM. Conclusion: In stable MS, most large lesions have a relatively increased glucose utilization and decreased NAA concentration. NAWM showed a significantly decreased NAA concentration compared to healthy subjects, but no difference in glucose metabolism. Active lesions in acute MS are also hyper-metabolic. This finding opens a new window on the classification of white matter lesions based on glucose utilization.
Long-lasting depression of soleus motoneurons excitability following repetitive magnetic stimuli of the spinal cord in multiple sclerosis patients
Authors: Nielsen Jørgen F , Sinkjær Thomas
Published: November 2009

The effect of repetitive magnetic stimulation at the spinal level on the soleus H-reflex amplitude was evaluated in II MS patients with lower limb spasticity and in nine healthy subjects. In MS patients stimulation with a train of 16 stimuli at 25 Hz induced a decrease in amplitude to 61.2 ± 25.7% of the unconditioned H-reflex amplitude at interstimulus interval (ISI) of 10 - 1000 ms (P < 0.0 1). The amount of decrease in H-reflex amplitude was highly dependent on the stimulation intensity and the placement of the coil, and to a lesser extent influenced by the stimulation frequency. No decrease in motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation was seen following trains of 16 stimuli at mid-thoracic in contrast to the post-stimulation depression in H-reflex amplitude which could imply that mechanisms acting at presynaptic level were involved. In response to repetitive magnetic stimuli for 5 min, a long-lasting decrease in H-reflex amplitude to a level of about 70% of the pre-stimulation H-reflex amplitude occurred in MS patients (P< 0.01 ). A similar although not significant decrease was observed in healthy subjects. We propose that long-lasting depression of the soleus H-reflex amplitude after repetitive magnetic stimuli is due to long-term depression of the synaptic transmission.
The MS impairment scale: a pragmatic approach to the assessment of impairment in patients with multiple sclerosis
Authors: Ravnborgl M. , Grønbech-Jensen M. , Jønsson A.
Published: November 2009

We developed a measurement scale for assessment of impairment in MS patients (MSIS) in accordance with the recommandations of WHO. The items were kept close to a standard neurologic examination, and a short battery of cognitive tests was added. Normality was assigned to the value, zero, and the theoretical maximum score was 204. Two-hundred and ten multiple sclerosis (MS) patients were rated by one neurologist on the MS Impairment Scale (MSIS), the Extended Disability Status Scale (EDSS), and the Ambulation Index (AI). The median MSIS score was 52 (5- 147), the median EDSS 6.5 (1 - 9.5), and the median Al 5 (1-5). The relation between the MSIS scores and the EDSS was best described by an exponential function (non-linear regression coefficient, R=0.87). Sixty-two of the patients were reexamined and rated by another neurologist The interrater reliability coefficient (R) of the MSIS was 0.95, of the EDSS 0.91, and of the Al 0.94. Forty patients were examined twice by the first neurologist The intrarater reliability coefficient was 0.97 for the MSIS, 0.95 for the EDSS, and 0.98 for the Al. The MSIS is easy to use and is robust to observer dissimilarities. It has a monomodal univariate distribution and has a better discriminatory power than the EDSS, especially in the EDSS range 6 - 9, while the interrater reliability of the MSIS is at least as good as that of the EDSS and the Al.
Promotion of endogeneous remyelination in Multiple Sclerosis
Authors: Lucchinetti CF , Noseworthy JH , Rodriguez M.
Published: November 2009

Studies in both human and experimental models demonstrate that myelin repair occurs in the central nervous system and is a normal physiologic response to myelin injury. However, remyelination in MS is often incomplete and limited. The outcome of an actively demyelinating lesion depends on the balance between factors promoting myelin destruction and myelin repair. Experimental models of CNS demyelination provide an opportunity to investigate the morphologic, cellular and molecular mechanisms involved in remyelination. This review focuses on experiments using the Theiler's virus model of demylination which indicate that manipulation of the immune response has the potential to promote endogenous CNS remyelination and functional recovery in MS.
Toward a transgenic mouse model of remyelination
Authors: Ferraresi S. , Lorenzetti I. , Nemni R. , Kamholz J. , Feltri ML , Wrabetz L.
Published: November 2009

The molecular mechanisms necessary for remyelination by oligodendrocytes remain unexplored. We previously characterized a myelin basic protein promoter-lacZ (MBP-lacZ) transgene whose expression is regulated uniquely during development, and also in pathological situations, suggesting that it may be a useful reporter of molecular mechanisms during remyelination. As a first step toward creating a transgenic mouse model of remyelination, we cultured oligodendrocytes from these transgenic mice and showed that expression of MBP-lacZ appeared in parallel with a marker of oligodendrocyte maturation, galactocerebroside (GC). In addition, basic fibroblast growth factor blocked the expression of both MBP-lacZ and GC in these cells. Therefore, expression of MBP-lacZ reflects not only the developmental stage of oligodendrocytes, but also extrinsic influences on oligodendrocytes. These data suggest that MBP-lacZ may be a useful marker in transgenic mouse models of remyelination.
Treatment of inflammatory neuropathy
Authors: Hughes R.A.C. , Gabriel C.M. , Gregson N.A. , Smith K.J.
Published: November 2009

Experimental autoimmune neuritis (EAN) provides an accurate model for understanding the mechanism of acute and chronic inflammatory demyelinating polyradiculoneuropathy (AIDP and CIDP). Treatments aimed at every stage of the immune process in EAN have been effective in inhibiting or treating the disease, including antibodies directed against cell adhesion molecules on the endothelium, inhibition of T cells, removal or blockade of antibodies, depletion of complement and interference with the release or action of macrophage effector molecules. In human disease the only proven treatments are plasma exchange and intravenous immunoglobulin (IVIg) in AIDP, and either of these regimens and also corticosteroids in CIDP. However the outcome from AIDP and CIDP remains unsatisfactory with existing immunosuppressive regimens. This problem arises from the fact that while demyelination appears to be effectively and promptly repaired by remyelination, it may be accompanied by axonal degeneration which can cause severe persistent disability. In addition to limiting demyelination, it will also be important to develop strategies to protect axons from degeneration and to enhance regeneration.
Immunomodulation and remyelination: two aspects of human polyclonal immunoglobulin treatment in immune mediated neuropathies?
Authors: van Schaik IN , Vermeulen M. , Brand A.
Published: November 2009

Intravenous immunoglobulin is used in inflammatory demyelinating diseases of the peripheral as well as the central nervous system. It is not known which mechanism(s) accounts for the beneficial effect observed in these diseases. The immunomodulatory effects of IVIg in two different models of T and B cell activation were investigated. IVIg inhibited a predominantly cellular immune response of the Th 1 type, which was partially reversed by addition of Th 1 cytokines. In contrast, in a model, which leads to B cell differentiation and antibody production, a synergistic stimulatory effect of IVIg and Th2 cytokines was observed. The ability of IVIg to interfere with cell proliferation and to manipulate the Th 1/Th2 profile will have consequences for the induction, character, and amplification of an immune response. Apart from the immunomodulatory effects, evidence shows that IVIg promote remyelination not only by abrogation of the auto-immune attack but also by an effect on glial cells. We showed that IVIg induce growth arrest of normal human fibroblasts and Schwann cells. In fibroblasts this growth arrest is accompanied by upregulation of GAS-3/PMP-22 mRNA. The implications of this finding are discussed. Further studies in human Schwann cells are imperative to prove the hypothesis that IVIg directly stimulates remyelination.
Neurosteroids, with special reference to the effect of progesterone on myelination in peripheral nerves
Authors: Baulieu E-E. , Schumacher M.
Published: November 2009

Some steroids are synthesized within the central and peripheral nervous system, mostly by glial cells. These are known as neurosteroids. In the brain, neurosteroids have been shown to act directly on membrane receptors for neurotransmitters. For example, progesterone inhibits the neuronal nicotinic acetylcholine receptor, whereas its 3α,5α-reduced metabolite 3α,5α-tetrahydroprogesterone (allopregnanolone) activates the A γ-aminobutyric acid receptor complex. Besides these effects, neurosteroids also regulate important glial functions, such as the synthesis of myelin proteins. Thus, in cultures of glial cells prepared from neonatal rat brain, progesterone increases the number of oligodendrocytes expressing the myelin basic protein (MBP) and the 2',3'-cyclic nucleotide-3'-phophodiesterase (CNPase). An important role for neurosteroids in myelin repair has been demonstrated in the rodent sciatic nerve, where progesterone and its direct precursor pregnenolone are synthesized by Schwann cells. After cryolesion of the male mouse sciatic nerve, blocking the local synthesis or action of progesterone impairs remyelination of the regenerating axons, whereas administration of progesterone to the lesion site promotes the formation of new myelin sheaths.
Imaging of remyelination
Authors: Barkhof Frederik
Published: November 2009

Now that the concept of remyelination is gaining acceptance in MS, there is a need for a paraclinical marker to monitor remyelination in MS, for example to study the effect of therapeutical interventions. At present there is no known imaging marker for remyelination. While positron emission tomography (PET) has ample sensitivity and specificity, an appropriate tracer is lacking and spatial resolution is poor. Magnetic resonance (MR) imaging has superior sensitivity and spatial resolution, but the standard techniques lack specificity. Conventional T2-weighted images will most probably still appear abnormal in an area of remyelination. Among several newer MR techniques that are more specific, magnetization transfer contrast is the best candidate with regards to imaging remyelination. There is a strong need for an appropriate animal model and for histopathological confirmation to be able to further develop both PET and MR.
Remyelination in multiple sclerosis
Authors: Lassmann Hans , Brück Wolfgang , Lucchinetti Claudia , Rodriguez Moses
Published: November 2009

Stimulation of remyelination in multiple sclerosis lesions may be one possible therapeutic approach. However, since the pathology and pathogenesis of multiple sclerosis may be heterogeneous, it is important to analyze in what patients and at what stages of the disease such a therapy can be reasonable and feasible. Spontaneous remyelination is pronounced in some MS patients. The extent of remyelination correlates well with the presence of oligodendrocytes in the lesions. Yet, the source and origin of the remyelinating cells is still unclear. These may be derived from either undifferentiated progenitor cells or, in part from mature oligodendrocytes, that have escaped destruction during lesional activity. Complete remyelination of plaques is possible, leading to the formation of 'shadow plaques'. No reliable data are available at present on the frequency of remyelination in different forms of MS. However, most studies agree that remyelination is especially prominent at the early stages of the disease, whereas it is sparse after several years of disease duration. In addition, very little remyelination is found in cases of primary progressive MS.
Treatment effects of monthly intravenous immunoglobulin on patients with relapsing - remitting Multiple Sclerosis: Further analyses of the Austrian immunoglobulin in MS Study
Authors: Fazekas Franz , Deisenhammer Florian , Strasser-Fuchs Siegrid , Nahler Gerhard , Mamoli Bruno
Published: November 2009

Recently, the Austrian Immunoglobulin in Multiple Sclerosis (AIMS) study showed patients with relapsing - remitting multiple sclerosis to benefit from repeated administration of intravenous immunoglobulin (IVIg). To provide a more detailed understanding of IV/g's action we performed further analyses on the time course of treatment effects and in regard to the impact of clinical disability at study entry on patients' response to medication. The AIMS trial was a randomized, placebo-controlled, double blind, multicenter trial. It included 148 patients (IVIg : 75; placebo 73) who suffered from relapsing-remitting MS, were 15-65 years old and scored from I -6 on the Expanded Disability Status Score (EDSS). IVIg was given over 2 years in a monthly dosage of 0.15 - 0.2 g/kg body weight. Within the first 6 months of the trial clinical disability of IVIg treated patients improved significantly from a baseline EDSS of 3.33 ± 1.38 to a score of 3.05 ± 1.73 (P=0.002). This improvement was retained over the subsequent 18 months of the trial (final EDSS: 3.09 ± 1.62). In contrast, placebo-treated patients showed a slight trend for deterioration over the study period (baseline EDSS: 3.37± 1.67; final EDSS: 3.49± 1.83). IVIg treatment was associated with a significant reduction of relapses throughout the study which was independent of the patients' disability at baseline. The observation of clinical improvement in the early phase of IVIg medication may suggest the activation of repair mechanisms such as the promotion of remyelination while immunoregulatory effects would be expected as the cause of fewer exacerbations throughout the AIMS study. These hypotheses need to be tested in future trials.
A double-blind, cross-over trial of intravenous immunoglobulin G in multiple sclerosis: Preliminary results
Authors: Sørensen P. Soelberg , Wanscher B. , Schreiber K. , Blinkenberg M. , Jensen C.V. , Ravnborg M.
Published: November 2009

We enrolled 25 patients with relapsing-remitting or relapsing progressive multiple sclerosis (MS) in a randomized placebo-controlled double-blind study of intravenous immunoglobulin G (IVIG). IVIG Iglkg daily for 2 days was administered every 4 weeks for 24 weeks. Seventeen patients completed the whole trial, whereas eight patients discontinued the trial; four during IVIG treatment and four on placebo. Of the 17 patients who completed the trial, II had no exacerbations during IVIG treatment compared with only six on placebo (P=0.05). The total number of exacerbations in the IVIG period was I / and in the placebo period 15 (NS), and the number of severe exacerbations requiring treatment with intravenous methylprednisolone was four during treatment with IVIG and six on placebo (NS). The results suggest that IVIG treatment may be of beneft for prevention of exacerbations in patients with relapsing MS.
Intravenous immunoglobulin (IVIG) treatment for patients with primary or secondary progressive multiple sclerosis - outline of a double-blind randomized, placebo-controlled trial
Authors: Poehlau D. , Federlein J. , Postert T. , Sailer M. , Bethke F. , Kappos L. , Haas J. , Przuntek H.
Published: November 2009

We present the design of a double-blind, randomised placebo-controlled phase III study to evaluate safety and efficacy of IVIG in the treatment of patients suffering from primary or secondary chronic progressive multiple sclerosis. The primary endpoint is disability. Two measures of disability were chosen in order to assess the primary end point: (a) sustained improvement (assessed at month 6, confirmed at month 9) and (b) progression to increasing disability of the disease (sustained for 3 months) at any time during the course of this 2 years study. The disability is measured by the Extended Disability Status Scale (EDSS). Secondary end points include the assessment of visual function, functions of the upper extremity, cognitive functions, depression and quality of life.
A shift in encephalitogenic T cell cytokine pattern is associated with suppression of EAE by intravenous immunoglobulins (IVIg)
Authors: Pashov Anastas , Bellon Blanche , Kaveri Srini V , Kazatchkine Michel D
Published: November 2009

Pooled human polyspecific IgG preparations for intravenous use (IVIg) have been used in a number of antibody mediated autoimmune diseases and recently in some T cell mediated disorders including multiple sclerosis, birdshot retinopathy and rheumatoid arthritis. Furthermore, IVIg has been proven beneficial in the corresponding animal models, i.e. experimental autoimmune encephalomyelitis (EAE), experimental autoimmune uveoretinitis and adjuvant arthritis respectively. The exact mechanisms for IVIg adion in T cell mediated disorders are still poorly understood. There is evidence that IVIg treatment in vitro and in vivo decreases or changes the kinetics of the secretion by normal PBMC of a number of cytokines and anti-proliferative effect of IVIg on T cells in vitro and in vivo has also been reported. It remains unclear though to what extent the IVIg effects in T cell mediated autoimmunity are related only to non-specifc T cell suppression and whether it also reshapes the autoimmune T cell cytokine profile. In this study we demonstrate that IVIg protects against EAE and that this beneficial effed is associated with a decreased proli feration of T cells specific for the immunizing antigen. Moreover, we show that these antigen-specific cells produce low amount of Th /-type cytokines and transfer an attenuated EAE
Schwann cell transplantation and myelin repair of the CNS
Authors: Evercooren A. Baron-Van , Avellana-Adalid V. , Lachapelle F. , Liblau R.
Published: November 2009

Studies with experimental models of dysmyelination and demyelination have shown that rodent Schwann cells including a Schwann cell line, transplanted in the central nervous system compete with host oligodendrocytes to remyelinate denuded central axons of the spinal cord. The myelin produced by transplanted SC around these central nervous system axons is structurally normal and restores, secure nerve conduction. In the presence of a favorable substrate, transplanted Schwann cells migrate over considerable distances (several mm) and are recruited by a demyelinated lesion which they will partially repair. Thus Schwann cells, which can also support axonal growth, may be instrumental in central nervous system repair. In addition, the possibility of obtaining large quantities of human and non-human primate Schwann cells, makes it possible to consider autologous Schwann cell transplantation as a potential therapy for demyelinating or traumatic diseases. The various differences which may exist between rodents and humans, however, require further investigation of this possibility in a non-human primate model of demyelination. These experiments should provide not only insights on the potential of autologous transplantation in primates but also a better understanding of the process of central remyelination.
Inhibition of oligodendrocyte precursor motility by oligodendrocyte processes: implications for transplantation-based approaches to multiple sclerosis
Authors: Jefferson Samantha , Jacques Thomas , Kiernan BW , Scott-Drew Suzanna , Milner Richard , ffrench-Constant Charles
Published: November 2009

Transplantation of oligodendrocyte precursor cells represents a promising approach to the treatment of the chronic demyelinated lesions of multiple sclerosis. In view of the multi-focal nature of the disease it will be necessary for the transplanted oligodendrocyte precursor cells to migrate through normal white matter between lesions. Work in other systems has shown that differentiated oligodendrocytes within white matter express molecules inhibitory for axon outgrowth. In light of this we have examined the effect of oligodendrocytes on the migration of oligodendrocyte precursors in vitro using time lapse video microscopy. We find that oligodendrocytes induce collapse and loss of motility in oligodendrocyte precursor processes, with this effect being lost as oligodendrocytes undergo programmed cell death. We conclude that the inhibitory factors present on differentiated oligodendrocytes may prevent effective migration between lesion in vivo, and that strategies to overcome this inhibition may be required for successful repair.
Lymphocyte-endothelial cell interactions in multiple sclerosis: disease specificity and relationship to circulating tumour necrosis factor-α and soluble adhesion molecules
Authors: Vora AJ , Kidd D. , Miller DH , Perkin GD , Hughes Rac , Ellis BA , Dumonde DC , Brown KA
Published: November 2009

This study addressed two questions: first, whether the supranormal adherence of blood lymphocytes from patients with multiple sderosis (MS) to endothelial cell monolayers treated with tumour necrosis factor-α (TNFα) was a feature common to other inflammatory disorders; and second, whether the adherence properties of blood lymphocytes from MS patients were related to changes in disease activity and to levels of circulating TNFα and soluble adhesion molecules. In the first part of the investigation, lymphocytes from I 4 patients with MS were more adherent to TNFα-treated endothelial cells (P < 0.01) than those from healthy controls, whereas the adherence properties of lymphocytes from 12 patients with rheumatoid arthritis, eight patients with psoriasis and ten patients with neurological diseases other than MS were normal. In the second phase of the work, measurement of the adhesive properties of lymphocytes isolated at monthly intervals from a further six MS patients over a 5 - 8 month period, found that changes in binding to TNFα-treated endothelial cells, directly paralleled changes in circulating levels of TNFα (r =0.77; P < 0.001) and soluble vascular cell adhesion molecule-I (sVCAM-I) (r= 0.67; P= 0.001). An increase in disease activity, measured by T2-weighted and gadolinium-enhanced magnetic resonance imaging of the central nervous system (CNS), occurred in two patients and was associated with heightened lymphocyte adhesiveness and a rise in serum TNFα levels. Further analysis of the 34 serum samples from the six MS patients revealed a direct relationship between the concentration of sL-selectin and soluble intercellular adhesion molecule- (sICAM-I) (r= 0.65; P < 0.001) and between sL-selectin and sTNFα (r =0.42; P < 0.02). These findings support the view that disease activity in MS is associated with an increased adhesive interaction of blood lymphocytes with vascular endothelium at inflammatory sites within the CNS.
Interferon gamma producing blood lymphocytes are decreased by interferon beta therapy in patients with multiple sclerosis
Authors: Petereit HF , Bamborschke S. , Esse AD , Heiss WD
Published: November 2009

Objective: We studied the individual course of interferon gamma producing blood lymphocyte count (IFGC) of 15 multiple sclerosis patients started on 8 MIU beta interferon administered subcutaneously each other day. Methods: Mononuclear blood cells were prepared before treatment and on day 3, 9, 15, as well as after month 1, 2, 3 and 4 of therapy. After stimulation intracellular interferon gamma was detected with monoclonal fluorescent antibodies and measured by flowcytometry. IFGC is given as percentage of all gated lymphocytes. Results: forty-eight hours after first interferon beta application the mean IFGC dropped significantly from 11.37 to 7.09 (P <0.05) and to 4.22 within 4 months. Whereas the majority of patients showed a decrease of IFGC from the beginning of therapy, in three of the 15 patients a transient increase of IFGC was seen suggesting a different response to immunomodulatory therapy. Conclusions: Interferon gamma producing lymphocyte count might be a useful tool to determine the biological effect of interferon β therapy in multiple sclerosis patients.
Neutralising and binding anti-interferon-β-1 b (IFN-b-1 b) antibodies during IFN-β-1 b treatment of multiple sclerosis
Authors: Kivisäkk P. , Alm GV , Tian WZ , Matusevicius D. , Fredrikson S. , Link H.
Published: November 2009

Interferon-β-1b (IFN-β-1b) is an immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-β-1b could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-β-1b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-β-1b antibodies, presently not believed to impede the clinical efficacy of IFN-β-1b, were demonstrated by an immunoassay in some patients already after I month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be an early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-β-1a and natural IFN-β were also found in a majority of IFN-β-1b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-β-1b for 1 -23 months had elevated numbers of anti-IFN-β-1b-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-β-1 b is immunogenic in MS patients. High levels of anti-IFN-β-1b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-β-1b antibodies might also occur spontaneously.
Coping with general and disease-related stressors by patients with multiple sclerosis: relationships to psychological distress
Authors: Jean VM , Beatty WW , Paul RH , Mullins L.
Published: November 2009

This study examined the relationships between coping styles and psychological distress in a non-institutionalized sample of individuals with multiple sclerosis (MS). The MS sample completed a measure of psychological distress and identified coping strategies utilized for stressors that were disease-related and general in nature. They also self-reported their perceived efficacy of the coping strategies utilized for both stressors. Individuals with MS exhibited greater levels of depression and other indices of psychological distress than demographically matched controls but the patterns of coping strategies endorsed and the ratings of coping effectiveness were similar for the two groups. When coping with disease-related stressors, individuals with MS utilized coping strategies that were more emotion-focused and dependent but no less effective than when the same patients coped with general stressors. Within the MS group, high levels of psychological distress were positively correlated with the use of emotion-focused coping strategies, but were unrelated to the use of problem-focused strategies. Most individuals with MS appear to be able to modify their coping strategies to adapt to varying sorts of stressors.
Inter-rater variability in reporting enhancing lesions present on standard and triple dose gadolinium scans of patients with multiple sclerosis
Authors: Filippi M. , Barkhof F. , Bressi S. , Yousry TA , Miller DH
Published: November 2009

In this study we evaluated and compared the inter-rater variabilities in detecting enhancing lesions in patients with MS after injection of a standard dose (s.d.) and a triple dose (TD) of gadolinium (Gd). Enhanced magnetic resonance imaging (MRI) were obtained in 15 patients, consisting of T1weighted images 5 to 7 min after the injection of the s.d. (0. I mmol/kg) of Gd and, after an interval of 6 to 24 h, 5 to 7 min after the injection of the TD (0.3 mmol/kg). An additional scan I h after the TD injection (delayed scanning - DS) was obtained in 11 patients. The scans were independently evaluated in a random order by four observers. Lesions were counted and scored according to size and location. The level of inter-observer concordance was very high for reporting the total numbers of enhancing lesions, their sizes and sites for the three experimental conditions. No significant differences were found in inter-observer variability in reporting the total number of enhancing lesions and their location in different brain sites in the three conditions. Our data indicate that the gain in sensitivity in detecting enhancing lesions in MS with the TD is not counteracted by a loss in reproducibility. This is important in planning clinical trials in which the number of enhancing lesions is used as a measure of outcome.
Treatment of multiple sclerosis with high-dose corticosteroids may prolong the prothrombin time to dangerous levels in patients taking warfarin
Authors: Kaufman Michael
Published: November 2009

Two patients who were taking warfarin experienced significant prolongations of the prothrombin time (protime) after treatment with high-dose corticosteroids for rapid progression of MS. This complication of therapy is potentially life-threatening.
Open label gabapentin treatment for pain in multiple sclerosis
Authors: Houtchens Maria K , Richert John R , Sami Arif , Rose John W
Published: November 2009

Pain is a frequent and distressing complaint in patients with multiple sclerosis (MS) and may present a difficult therapeutic problem. Conventional therapy is moderately effective and includes, among others, a variety of anticonvulsant medications. Gabapentin (Neurontin™) is a new generation antiepileptic drug which appears to be advantageous in treatment of intractable pain of reflex sympathetic dystrophy. This study investigates the benefits of open-label treatment with gabapentin for pain control in 25 patients with MS. Excellent to moderate pain relief was obtained in a substantial number of patients. Throbbing pains, pins and needles, and cramping pains responded best, and dull aching pains responded least to the medication. There was no significant change in distribution and type of pain as a result of this treatment Mild to moderate side effects were observed. Cautious escalation of the dose of gabapentin is advisable in MS patients. Further clinical trials with larger patient groups are recommended.
Depression, coping and level of neurological impairment in multiple sclerosis
Authors: Mohr David C , Goodkin Donald E , Gatto Nicole , Van Der Wende Judy
Published: November 2009

This study examined the relationship between coping and depression in multiple sclerosis patients, and how that relationship varies at different levels of physical impairment One-hundred and one patients with clinically definite MS were assessed using the Kurtzke Expanded Disability Status Scale (EDSS), the Ways of Coping Inventory (WCI) with three sub-scales developed by Wineman et al,25 and the Beck Depression Inventory (BDI). Depression was significantly higher at more advanced levels of neurologic impairment than at lower levels. Escape-Avoidance and Emotional Respite were positively related to level of depression. Planful Problem-Solving and Cognitive Reframing were negatively related to depression. An interaction between coping, depression, and level of neurologic impairment was observed in which Planful Problem-Solving and Cognitive Reframing were more strongly related to depression at higher levels of impairment The interaction effect for Escape-Avoidance and Emotional Respite with depression and level of impairment did not reach significance. It was concluded that there is a significant interaction between level of neurologic impairment, coping behaviors, and depression in patients with MS.
Antibodies to the axolemma-enriched fraction in the cerebrospinal fluid and serum of patients with multiple sclerosis and other neurological diseases
Authors: Rawes JA , Calabrese VP , Khan OA , DeVries GH
Published: November 2009

Antibodies to an axolemma-enriched fraction (AEF) antigen have been detected in the cerebrospinal fluid (CSF) and serum of patients with Multiple Sclerosis (MS) using an enzyme-linked immunosorbent assay (ELISA). A marginal elevation (P < 0.08) of anti-AEF lgG was found in MS CSF when compared with OND samples. When CSF was diluted to a standardized lgG concentration, the anti-AEF lgG level in MS CSF was significantly elevated (P=0.007) when compared to OND CSF. MS serum was also found to contain a significantly higher level (P < 0.00 I ) of anti-AEF lgG when compared to OND serum using the ELISA technique.
Failure of intravenous immunoglobulin to arrest progression of multiple sclerosis: a clinical and MRI based study
Authors: Francis Gordon S , Freedman Mark S , Antel Jack P
Published: November 2009

Due to the modest benefit, inconvenience and high cost of currently available therapies for MS, it is appropriate to seek alternative treatments. Based on anecdotal evidence suggestive of benefit for IVIG in MS, we conducted an open-label, unblinded protocol of IVIG in nine MS patients. The patients were given induction doses of IVIG followed by monthly boosters for I year and had clinical, MRI and CSF analyses performed. Patients included were both progressive and relapsing. There was no clinical benefit nor apparent MRI benefit utilizing this protocol. During treatment, the majority of patients continued to progress or have attacks and MRI demonstrated continued accumulation of T2-weighted lesions. CSF was unaffected by treatment
Identification of a Val I 45 IIe substitution in the human myelin oligodendrocyte glycoprotein: lack of association with multiple sclerosis
Authors: Rodriguez D. , Gaspera B. Della , Zalc B. , Hauw J-J. , Fontaine B. , Edan G. , Clanets M. , Dautigny A. , Pham-Dinh D.
Published: November 2009

Myelin/oligodendrocyte glycoprotein (MOG) is a major target antigen in experimental autoimmune encephalomyelitis and it has been suggested that it may as well play a key role in the demyelination process in multiple sclerosis (MS). As MOG variants could be pathogenic in autoimmune demyelinating diseases of the central nervous system, we analysed the coding sequence of MOG in MS patients and described a G→A transition occurring in exon 3 of the human MOG gene. The mutation predicts that isoleucine substitutes for a valine at codon I 45 (Val 145 lle) in the transmembrane region of the protein. This is the first aminoacid substitution reported in human MOG. The polymorphism can be detected by restriction enzyme digestion of genomic DNA or reverse-transcribed PCR amplified products, making it a simple tool to detect a potential implication of MOG alleles in susceptibility to MS by association study. The analysis of 83 unrelated MS patients and 82 unrelated healthy controls showed that the polymorphism is found in similar proportions in MS patients (18%) and controls (14.6%). It is therefore unlikely that the MOG Val 145 lle variant is responsible for genetic susceptibility to MS.
The influence of slice orientation on brain MRI lesion load measurement in multiple sclerosis
Authors: Rovaris M. , Sormanis MP , Rocca MA , Comi G. , Filippi M.
Published: November 2009

This study aimed at evaluating the influence of a different slice orientation on brain magnetic resonance imaging (MRI) lesion load in multiple sclerosis (MS). Fifteen MS patients were scanned obtaining both axial and sagittal conventional spin echo (24 slices; TR 2400, TE 30/80) brain MRI. The total lesion load (TLL) was assessed twice for each scan, using a semi-automated local thresholding technique and the same marked hardcopies. The mean TLL was 22734 mm3 for axial and 22003 mm3 for sagittal scans. The mean intra-observer coefficient of variation (COV) was 4.65% for the axial acquisitions and 4.52% for the sagittal acquisitions. This difference was not statistically significant (one-way ANOVA, P> 0.1). The lesion load was significantly higher from axial MRI as compared to the intra-observer variability (two-way ANOVA, P =0.01), but the fluctuations around this average difference between axial and sagittal scan TLL were significantly large (test for interaction, P < 0.00I). Our data indicate that the use of sagittal conventional MRI scans does not seem to be worthwhile for the quantitative assessment of lesion load in MS patients.
Telling Our Stories of Leadership: If We Don’t Tell Them They Won’t Be Told
Authors: Byrd Marilyn Y.
Published: November 2009

The purpose of this qualitative study is to bring the interlocking system of race, gender, and social class (intersectionality) to the conversation of leadership by examining the leadership experiences of 10 African American women in predominantly White organizations. According to the women in this study, disempowering encounters, being excluded from the good ole boy social network, being the only one, needing validation, and demythicizing (disrupting myth) stereotypical images were the most salient encounters that they experienced. Another finding from this study was the need for sociocultural theories such as Black feminist theory and critical race theory to explain and give voice to the everyday lived experiences of African American women leaders.