The esterolytic activity of a sample is routinely estimated by employing the pNpp assay (20). The basis of this assay procedure is the colorimetric estimation of pNp released as a result of enzymatic hydrolysis of pNpp at 405  nm. The substrate solution was prepared by adding solution

A (30  mg pNpp in 10  mL isopropanol) to solution Lorlatinib ic50 B (0.1  g gum arabic and 0.4  mL Triton X-100 in 90  mL of 50 mM Tris- HCl buffer, pH 8.0) with stirring. The mixture of 180 μL substrate solution and 20 μL enzyme solution was incubated at 37°C for 15  min. Absorbance was measured at 405  nm (A405) originating from p-nitrophenol, which was generated by the action of lipase. The substrate specificity of the purified enzyme was analyzed

using the following substrates of pNp-fatty acyl esters: decanoate (C10), palmitate (C16) and stearate (C18). The reactions were carried out as described above. The lipase activity of the sample was determined by incubation with tributyrin. The method described by Lotrakul and Dharmsthiti was used to examine activity (21). Briefly, 40 μL tributyrin was sonicated in 1.0  mL of 0.1 FK228 M Tris-HCl (pH 8.0) containing 1  mM calcium chloride for 3  min. After sonication, the solution was divided into four tubes (250 μL/tube). A different amount of purified protein (250 μL) was added to each tube and the reaction mixture incubated at 37°C for 6  hrs. After incubation, the reaction products were extracted by the addition of 0.5mL diethyl ether. The extract was concentrated by evaporation and applied to a silica gel plate (TLC Silica Gel 60; Merck KGaA, Darmstadt, Germany). Plates were developed with a 96:4:1 mixture (by volume) of chloroform:acetone:acetic acid. The spots of glycerides were visualized by exposure to 50% sulfuric acid vapor and then heating at 160°C for 30  min. The assay to test the thermostability of purified lipase was performed by heating the enzyme solution at 30°C, 40°C, 50°C,

60°C, 70°C, Anacetrapib 80°C, and 100°C for 10  min. The remaining activity after heating was assayed as described above using pNp-palmitate as a substrate. To determine the nucleotide sequence of the target protein of A. sorbria 288, two sets of oligonucleotides were designed with reference to the nucleotide sequence of extracellular lipase of A. hydrophila ATCC7966. The extracellular lipase of A. hydrophila ATCC7966 is composed of 805 amino acid residues (2415 nucleotides). The first set of oligonucleotides was composed of oligomer-1 (5′-TCTGCACGTCAAACTCTTCG-3′, forward) and oligomer-2 (5′-TCGAACTTGAACAGGGCATC-3′, reverse). The DNA fragment amplified by the first set of oligonucleotides covers the region from −  467 to 1784 of the extracellular lipase gene (+  1 nucleotide is A of the initiation codon of translation). The second set was composed of oligomer-3 (5′-GGCAAGCCGCTGGATGCCGA-3′, forward) and oligomer-4 (5′-CGCTGTTTGGCGGCCTCTCC-3′, reverse).

Doxycycline

at 10 and 20 μM concentrations Selleck Target Selective Inhibitor Library produced a 13% and 39% reduction, respectively (data not shown). The effects of doxycycline on MMP-9 levels were further analyzed by Western blotting using monoclonal antibody (mAb) against MMP-9 under a reducing condition (Fig. 5). The band density was scanned with a laser densitometer to quantify the effect of doxycycline on MMP-9 levels released into the CM. Ten and 20 μM doxycycline reduced MMP-9 protein produced by lipopolysaccharide-treated macrophages by 14% and 46%, respectively. The reduced level of MMP-9 (92 kDa) protein shown by Western blot was consistent with the functional activity of 92-kDa gelatinase shown by gelatin zymography. Using a nonreduced conditioned medium, the high-molecular-weight protein

shown in the gelatin zymograms reacted with mAb against MMP-9, and after reduction with 5% 2-mercaptoethanol, this immunoreactive band disappeared (data not shown). This high-molecular-weight protein could be a dimer of 92-kDa gelatinase (gelatinase B). Interstitial collagenase activity was measured by SDS-PAGE/fluorography using [3H]-collagen as a substrate (Fig. 6). The collagenase activity was measured after activation of the proMMP by 1 mM APMA (Golub et al., 1995). As shown in Fig. 6, the macrophage-conditioned media exhibited classic collagenase activity because the neutral proteinase degraded the α1 (1) and α2 (1) components of the type I collagen into 3/4 (αA) and 1/4 (αB) degradation fragments. Degradation of [3H] collagen was inhibited Trichostatin A purchase by 10 and 20 μM doxycycline. The SDS-PAGE/fluorography was

scanned with a laser densitometer to quantify the effect of doxycycline on collagenase activity released into the CM. When lipopolysaccharides were cultured with macrophage, doxycycline at 10 and 20 μM concentrations appeared to reduce the interstitial collagenase activity in a dose–response 4��8C manner. When macrophages were incubated with lipopolysaccharide on [3H]-fucose-labeled ECM, 20% of the matrix-associated fucose radioactivity was solubilized. Doxycycline at 20 and 50 μM concentration reduced ECM from degradation by 47.6% and 61.9%, respectively (Fig. 7). During the inflammatory response, after the initial polymorphonuclear leukocyte emigration into the lesion begins to wane, mononuclear phagocytes are attracted from the vasculature by chemotactic signals and migrate into the tissues. These infiltrating activated monocytes/macrophages then release proteinases and cytokines, which can directly or indirectly cause tissue damage. When doxycycline was added to the monocyte-derived macrophages in cell cultures at 10 and 20 μM concentrations, it reduced both interstitial collagenase and 92-kDa gelatinase B activities. This reduction could be a result of reduced gene expression, reduced secretion and/or increased proenzyme degradation.

Electromyography, nerve conduction studies, and serum and urinary amino acid analysis were unremarkable. Analysis of CSF revealed mild elevation of IgG (7.5 mg/dL). Bone marrow examination was inconclusive. Activities of sphingomyelinase and hexosaminidase were within normal limits. Abdominal ultrasonography was negative for hepatosplenomegaly, as it was during www.selleckchem.com/products/PLX-4720.html the

entire course of the illness. By the age of 14 years, the patient had become tetraparetic. A gastrostomy tube was placed because of increasing dysphagia at 16 years of age. He subsequently became bedridden with total dependence. At age 22, a tracheostomy was performed and respiratory Roscovitine mouse support with mechanical ventilation was started. Brain MRI performed at 31 years of age revealed marked brain atrophy, especially in the frontotemporal lobes, hippocampus, brainstem and cerebellum (Fig. 1). In contrast to severe involvement of the frontotemporal region, the parieto-occipital region was relatively spared

(Fig. 1). Seizures were well-controlled by phenobarbital and carbamazepine, and no apparent episodes occurred during the last 12 years of his life. The last EEG was performed at age 31 and showed no epileptic discharge. He died from acute pancreatitis at age 37 years. The clinical diagnosis at the time of death was unclassified neurodegenerative disease of childhood onset.

An autopsy was performed 3-mercaptopyruvate sulfurtransferase 3 h after death. All organs were fixed with 10% phosphate-buffered formalin. Paraffin-embedded tissue blocks were cut into 6 μm sections, which were then stained with HE. CNS tissue sections were subjected to KB staining. The Gallyas-Braak silver stain and immunohistochemistry were performed on selected CNS sections. For filipin staining, liver tissue was embedded in O.C.T. compound (Sakura Finetechnical Co., Tokyo, Japan) and cryosections of 10 μm thickness were cut using a Bright OTF Cryostat (Bright Instrument Co. Ltd, Huntingdon, UK). Sections were immersed in 10% phosphate-buffered formalin for 10 min at 4°C, washed with distilled water three times, and incubated with 0.1 mg/mL filipin III (Cayman Chemical, Ann Arbor, MI, USA) for 1 h at room temperature in the dark. After rinsing in PBS, sections were coverslipped using a SlowFade Antifade kit (Invitrogen Life Technologies Corp., Carlsbad, CA, USA) and fluorescent images were acquired using a fluorescent microscope (Axiovert 200 M, Carl Zeiss Co. Ltd, Oberkochen, Germany).

cruzi antigens, including a recombinant antigen encoding the N-terminal 65 kDa portion of Trypomastigote surface antigen-1 (TSA-1). With at least six known genetically Selleckchem Kinase Inhibitor Library distinct T. cruzi lineages, variability between the different lineages poses a unique challenge for the development of broadly effective therapeutic vaccine. The variability across the major lineages in the current vaccine candidate antigen TSA-1 has not previously been addressed. To assess the variation in TSA-1, we cloned and sequenced TSA-1 from several different T. cruzi strains representing three of the most clinically

relevant lineages. Analysis of the different alleles showed limited variation in TSA-1 across the different strains and fit with the current theory for the evolution of the different lineages. Additionally, minimal variation in known antigenic epitopes for the HLA-A

02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1. “
“CD73/ecto-5′-nucleotidase dephosphorylates extracellular AMP into adenosine, and it is a key enzyme in the regulation of adenosinergic signaling. The contribution of host CD73 to tumor growth and anti-tumor immunity has not been studied. Here, we show that under physiological conditions CD73-deficient mice had significantly elevated ATPase and ADPase activities in LN T cells. In a melanoma model, the growth of primary tumors and formation of metastasis were significantly attenuated in mice lacking CD73. Among tumor-infiltrating leukocytes there were fewer Tregs and mannose receptor-positive macrophages, and increased KPT-330 concentration IFN-γ and NOS2 mRNA production in CD73-deficient mice. Treatment of tumor-bearing animals with soluble apyrase, an enzyme hydrolyzing Farnesyltransferase ATP and ADP, significantly inhibited tumor growth and accumulation of intratumoral Tregs and mannose receptor-positive macrophages in the WT C57BL/6 mice but not in the CD73-deficient mice. Pharmacological inhibition of CD73 with α,β-methylene-adenosine-5′-diphosphate in WT mice retarded tumor progression similarly to the

genetic deletion of CD73. Together these data show that increased pericellular ATP degradation in the absence of CD73 activity in the host cells is a novel mechanism controlling anti-tumor immunity and tumor progression, and that the purinergic balance can be manipulated therapeutically to inhibit tumor growth. Extracellular ATP, ADP and adenosine are powerful signaling molecules known to play key roles in controlling platelet aggregation, vascular tone and inflammatory responses 1–3. The purines released from damaged cells during pathological conditions function as a classical danger signal for the immune system. However, purines are also released from normal cells to the extracellular environment through several active mechanisms.

It is practical, includes up to date diagnostic techniques, and is beautifully illustrated throughout. In terms of the number and quality of the images I think it is easily one of the best neuropathology books currently available,

with the advantage that it covers both neoplastic and non-neoplastic focal lesions. The price of £188.89 (http://www.amazon.co.uk) reflects the quality of the finished product and, in my opinion, represents value for money. I would highly recommend it. “
“This is the 5th edition of Escourolle and Poirier’s Manual of Basic Neuropathology, published more than 40 years after the 1st edition and a decade after the previous RGFP966 mouse 4th edition. For this edition Professor Charles Duyckaerts has joined the editorial team – Professor Francoise Gray and Professor Umberto De Girolami, with an additional 32 contributing authors from France,

USA, UK, Germany, Brazil and Malaysia. Although the style and the paperback format of this latest edition remain unchanged from the previous one, there are obvious updates, not limited to the selleck compound change in colour of the book cover! Most of the chapters in the current book are fully revised, closely reflecting the new discoveries in the field of neuropathology over the past decade. In particular this relates to new findings in immunopathology, molecular biology and genetics, with concise updates on current classification, diagnostic approaches and applied methods for many of the described pathological processes. The book is divided in 14 chapters and a separate appendix. The first chapter covers basic pathology of the central nervous system. The following chapters describe the full spectrum of the various categories of neurological disorders, including neoplasia, trauma, vascular disease, infections, prion diseases, inflammatory demyelinating diseases (with emphasis on multiple sclerosis), degenerative diseases, acquired and hereditary metabolic disorders, congenital

malformations and perinatal diseases, pathology of skeletal muscle and peripheral nerve, and the pituitary gland. The appendix at the end of the book summaries Cobimetinib solubility dmso techniques used in neuropathology. In addition to a concise account of well-known methods related to adequate tissue removal and dissection, appropriate fixation of various types of specimens (including muscle and nerve), processing, embedding and staining (including histochemical, immunohistochemical and in-situ hybridization methods), more recently introduced laboratory techniques, such as histoblot and PET blot methods, are briefly mentioned. The appendix finishes with a brief but helpful description of macroscopic and microscopic artefacts encountered in routine practice. The text is written in a narrative style and, although each chapter is written by various contributing authors, the style and layout remains similar and therefore easy to read and enjoyable.

Various other end-points evaluating the efficacy of IgG therapy in patients with PI have been explored. Pulmonary https://www.selleckchem.com/products/ly2606368.html function has been studied [15–20],

but the lack of sensitivity of the available methods has prevented the wide use of this measure. The Chest CT in ADS Group (http://www.chest-ct-group.eu/), an international group of immunologists, pulmonologists and radiologists, has developed a methodology for improving the diagnosis of disease in patients with antibody deficiency syndrome. This group uses high-resolution chest computed tomography (CT) scanning along with a battery of lung function tests which are used to give a CT score to track the progression of lung disease. The potential

use of C-reactive protein (CRP) as an indicator of IgG therapy efficacy was discussed. CRP is an acute-phase protein produced in response to various stimuli involving tissue damage such as inflammation and infection. Serum CRP has been used extensively as a marker of bacterial infection [21]. However, due to its low specificity, its true diagnostic value in clinical practice has been questioned [22,23]. A retrospective, single-centre study was carried out to examine the association between CRP levels and clinical outcomes in patients with CVID on immunoglobulin replacement. The cohort consisted of 112 CVID patients selleckchem and was divided into three groups based on median CRP values (0–5, 5–10 and > 10 mg/l). There were 10 patients in the > 10 mg/l group. There were a large number of patients in both 0–5 and 5–10 mg/l groups and 12 patients were selected randomly from each group for the analysis. Five outcome parameters

were investigated: number of infections, number of serious Flavopiridol (Alvocidib) infections, number of antibiotic courses, days off sick and days in hospital. These parameters are also part of the quality of life data set in the ESID database [14]. The working hypothesis was that these outcome parameters would correlate positively with serum CRP levels. However, when considering CRP on a continuous scale, no strong evidence of an association between CRP and any of the parameters examined was found (Table 1). Only weak evidence of an association between CRP and the number of serious infections was observed, but this was not statistically significant (P = 0·08). The Spearman’s rank correlation coefficient between the two variables was positive, suggesting that the number of serious infections increased with increasing serum CRP level. When the CRP measurements were divided into three categories (0–5, 5–10 and > 10 mg/l), the Kruskal–Wallis analysis suggested that there was not enough evidence that any of the outcome parameters varied between CRP categories (Table 1).

It has been shown that the addition of erythrocytes to cultured slanDC blocks their capacity

to produce IL-12 and TNF-α via the interaction of CD47 on erythrocytes and the corresponding ligand signal regulatory protein α on slanDC.4 After slanDC leave the bloodstream and infiltrate the tissue, as it was shown in inflamed skin of AD lesions, the control by erythrocytes is lost. Our study suggests that histamine might take over this control function in the tissue because we could show that histamine reduces the highly pro-inflammatory capacity of slanDC, particularly via activation of the H4R. To be sure that histamine stimulation does not reduce cytokine production in general, we investigated IL-10 as a SCH727965 research buy cytokine DAPT in vitro that is associated with anti-inflammatory actions. Interleukin-10 reduces the production of IL-2, TNF-α, IFN-γ and co-stimulatory molecules and was shown to counteract the inflammatory response in allergic contact dermatitis.24 In our study we could not observe a significant effect of histamine receptor activation on the release of IL-10. As a result, it can be assumed that H4R and H2R stimulation on slanDC specifically down-regulate the production of the pro-inflammatory mediators TNF-α and IL-12, whereas the level of the anti-inflammatory mediator IL-10 is not affected. The differential regulation of cytokine release by histamine might

be explained by varying signalling processes involved. For example, it was shown that the activation of mitogen-activated protein kinase signalling mediates histamine-induced down-regulation of IL-12p70 in monocytes,15 but on the other hand induces IL-10 production in monocytes.25 Our observations fit the current understanding

of the role of the H4R on antigen-presenting cells. Several studies have shown that the H4R on DC has an anti-inflammatory role: on MoDC, monocytes and inflammatory dendritic epidermal cells the production of IL-12 and CCL2 was down-regulated after H4R activation.15–17 In response to the reduced presence of these mediators, Histamine H2 receptor Th1 polarization is impaired and a lower number of macrophages and T cells is attracted to the site of the immune response, respectively. We can draw the conclusion that the stimulation of the H4R on DC, and as shown here in particular on slanDC, could greatly reduce the inflammatory responses taking place in the course of inflammatory skin diseases like AD and H4R agonists therefore might represent potential therapeutic tools in these kinds of diseases. This study was supported by grants from the Deutsche Forschungsgemeinschaft DFG: Gu434/5-1 and GRK1441/1 and the European Community (COST action BM0806). Maria Gschwandtner was supported by a grant from the Hannover Biomedical Research School. The authors declare no conflict of interest.

3a). However, Neratinib solubility dmso one can envisage the detrimental effect of uncontrolled over-activation

in the immune system that may be experienced by the introduction of activating siglecs that recognize the same ligand as their inhibitory isoforms. This might explain the rapid de-selection of these newly ‘invented’ activating siglecs.23 For example, siglec-11 has been shown to display important neuroprotective properties, such as inhibition of production of pro-inflammatory mediators, interleukin-1β (IL-1β) and nitric oxide synthase-2 and phagocytosis in microglia, the resident macrophage in the brain.29 Engagement of siglec-16 in the brain with the same ligand as siglec-11, could trigger inappropriate immune and inflammatory responses. In fact, for siglec-16, equilibrium is observed between the wild-type and mutant alleles in the population. We could be witnessing a gradual phasing out of the new siglec-16 gene in humans or it might indicate that a balance

has already been achieved between the pathogenic pressure to keep siglec-16 in the population and the de-selective pressure against siglec-16 driven by its detrimental effects on immune activation22 (Fig. 3b). Besides siglec-16, three other recently characterized siglecs selleckchem possess charged transmembrane domains and can interact with DAP12: siglec-14 in humans,20,30 siglec-15 in human and mouse21 and siglec-H in rodents only.31–33 Like siglec-11 and siglec-16, human siglec-14 is paired with siglec-5 and both pairs of siglecs share high homology in their extracellular domains. A transmembrane domain in siglec-14, containing a charged arginine residue, allows siglec-14 to interact with DAP12, unlike siglec-5. Siglec-5 also contains inhibitory ITIM-like motifs, which siglec-14 lacks. Recent studies show a fusion at the genomic level in parts of the population between siglec-5 and siglec-14 that results in a functional deletion of siglec-14.30 Gefitinib mw This phenomenon is consistent

with the observation of strong de-selection imposed upon activating siglecs as discussed above. Siglec-1521 is different among the newly discovered potentially activating siglecs in two ways. First, it is conserved from mammals to fish.21 Second, siglec-15 is the only receptor in the siglec family that encodes both an ITIM and a charged transmembrane residue that has been shown to associate promiscuously with the positive signalling adaptor molecules, DAP10, DAP12 and Fc receptor γ-chain.21 It will be interesting to see how signalling through siglec-15 is regulated and whether siglec-15 survived such a long evolution because of its ability to trigger different types of signalling. Siglec-H is a rodent CD33rSiglec expressed specifically on plasmacytoid dendritic cells (pDCs) and is a good marker for pDCs.32 Siglec-H contains a transmembrane lysine residue and associates with DAP12.

Patients in whom the disease appears between the third and fifth decades belong to an intermediate type, and usually show ataxia and choreoathetosis (early-adult type). MRI findings of DRPLA are characterized by atrophic

changes in the cerebellum, pons, brain stem and cerebrum (Fig. 1a,b). High-signal lesions in the cerebral white matter, globus pallidus, thalamus, midbrain and pons on T2-weighted MRI have been often found in adult patients with long disease durations (Fig. 1c).8 At autopsy, the thickening of the skull is a significant feature of DRPLA. Macroscopically, the brain is generally small. The cerebrum, brain stem and cerebellum are DMXAA price relatively well proportioned in external GDC-0068 mouse appearance. The spinal cord

is proportionately small in size. There is no correlation between brain weight and clinical factors such as age at onset, age at death and disease duration, and between brain weight and CAG repeat size. On cut surface, the brain reveals atrophy and brownish-tan discoloration of the globus pallidus (Fig. 2), subthalamic nucleus (Luys body), and dentate nucleus. The atrophy of the brain stem tegmentum, being more marked in the pontine tegmentum, is also remarkable. The cerebral cortical atrophy is slight or negligible. However, almost every case shows mild to moderate dilatation of the lateral ventricle. Combined degeneration of the dentatorubral and pallidoluysian systems is the major pathological feature of DRPLA. The globus pallidus, especially the lateral segment (Fig. 3a), and the dentate nucleus are consistently involved, showing loss of neurons and astrocytosis. The subthalamic nucleus also shows loss of neurons (Fig. 3b). The loss of neurons is Abiraterone cost always milder than that of the lateral segment of the globus pallidus.

In the dentate nucleus, the remaining neurons are often swollen or shrunken with so-called “grumose degeneration”: numerous eosinophilic and argytophilic granular materials, which represent the secondary change of the axon terminals of Purkinje cells, accumulating around the somata and dendrites. In the red nucleus, definite astrocytosis is seen, but loss of neurons is usually not evident. In general, pallidoluysian degeneration is more marked than dentatorubral degeneration in the juvenile-type DRPLA, and the reverse is often seen in the late-adult type. The population of cerebral cortical neurons appears to be mildly or slightly decreased. In some cases, especially in the adult-onset cases, diffuse myelin pallor with slight gliosis is also evident in the white matter. In DRPLA, various other brain regions may be affected mildly or moderately, but it is also important to note that the substantia nigra, the locus ceruleus, the pontine nuclei and the cranial nerve nuclei, with the exception of vestibular nuclei, are well preserved. The gene for DRPLA was identified in 1994,9,10 and mapped to 12p13.

Adverse effects: in the Phase II clinical trial, severe adverse events occurred with similar frequency in both ocrelizumab treatment groups. Severe adverse events were systemic inflammatory response syndrome (SIRS), hypersensitivity reactions, oral herpes simplex, squamous cell carcinoma of the skin (based on a preexisting lesion) and fear. Moreover, one case of death occurred due to SIRS with high-dose ocrelizumab. Navitoclax solubility dmso Ofatumumab is a human monoclonal B cell-depleting anti-CD20 antibody. Preparations and administration: ofatumumab is currently

approved for the treatment of chronic lymphatic leukaemia. It is administered intravenously on days 1 and 15. Clinical trials: in a small Phase II trial (a double-blind, randomized, placebo-controlled, multi-centre, dose-finding

trial of ofatumumab in RRMS patients) a total of 38 patients with RRMS received either ofatumumab (2 × 100 mg, 2 × 300 mg or 2 × 700 mg i.v.) or placebo for 24 weeks and were switched to either placebo or ofatumumab for another 24 weeks, respectively. BMN 673 order Patients in both study groups exhibited a sustained reduction of inflammatory lesions on MRI at the end of the study [75]. Another Phase II trial (a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study to investigate the MRI efficacy and safety of 6 months’ administration of ofatumumab in subjects with RRMS) is currently ongoing to compare ofatumumab (1 × 3 mg, 1 × 30 mg or 1 × 60 mg s.c. every 12 weeks or 1 × 60 mg

s.c. every 4 weeks for a total of 24 weeks with subsequent observation for another 24 weeks) to placebo in approximately 200 patients with RRMS with regard to its impact on different MRI parameters as well as safety and tolerability [76]. To the best of our knowledge, there is currently no clinical trial that has evaluated ofatumumab in patients with CIDP. Adverse effects: in the Phase II clinical trial there were no dose-limiting toxic effects or unexpected safety risks with ofatumumab [75]. Daclizumab is a humanized, monoclonal selleck antibody which binds and inactivates the alpha-chain of the IL-2-receptor (CD25 antigen) on T cells. IL-2 is crucial for the activation and proliferation of T cells. Daclizumab is also supposed to increase the number of natural killer cells which, in turn, attack (autoreactive) T cells. Preparations and administration: daclizumab is administered subcutaneously every 2–4 weeks. Clinical trials: a Phase II trial (daclizumab in patients with active, relapsing MS on concurrent interferon-beta therapy – CHOICE) with 230 patients with RRMS compared daclizumab (2 mg/kg every 2 weeks or 1 mg/kg every 4 weeks s.c.) plus IFN-β-1a (3 × 44 μg/week) to placebo plus IFN-β-1a for 24 weeks. High- but not low-dose daclizumab reduced the number of newly occurring or enlarging gadolinium-enhancing lesions on MRI by 72% (P = 0·004) [77].