Search PubMed⌕ Search

Biomedical subjects

S Choi

Publications and source records attributed to S Choi.

At least 181 records · Page 10Linked to original sources

Inhibition of nitric oxide synthesis increases mortality in Sindbis virus encephalitis.

Sindbis virus (SV) is an alphavirus that causes acute encephalomyelitis in mice. The outcome is determined by the strain of virus and by the age and genetic background of the host. The mortality rates after infection with NSV, a neurovirulent strain of SV, were as follows v: 81% (17 of 21) in BALB/cJ mice; 20% (4 of 20) in BALB/cByJ mice (P < 0.001); 100% in A/J, C57BL/6J, SJL, and DBA mice; and 79% (11 of 14) in immunodeficient scid/CB17 mice. Treatment with Nomega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthetase (NOS) inhibitor, increased mortality to 100% (P < 0.05) in NSV-infected BALB/cJ mice, to 95% (P < 0.001) in BALB/cByJ mice, and to 100% in scid/CB17 mice. BALB/cJ and BALB/cByJ mice had similar levels of inducible NOS mRNA in their brains, which were not affected by L-NAME or NSV infection. Brain NOS activity was similar in BALB/cJ and BALB/cByJ mice before and after infection and was markedly inhibited by L-NAME. NSV replication in the brains of BALB/cJ mice, BALB/cByJ mice, and mice treated with L-NAME was similar. Treatment of N18 neuroblastoma cells with NO donors S-nitroso-N-acetylpenicillamine or sodium nitroprusside in vitro before infection increased cell viability at 42 to 48 h compared with untreated NSV-infected N18 cells with little effect on virus replication. These data suggest that NO protects mice from fatal encephalitis by a mechanism that does not directly involve the immune response or inhibition of virus growth but rather may enhance survival of the infected neuron until the immune response can control virus replication.

Alphavirus Infections↗

Ventriculostomy infections: the effect of monitoring duration and catheter exchange in 584 patients.

The investigators undertook a retrospective analysis of ventriculostomy infections to evaluate their relationship to monitoring duration and prophylactic catheter exchange. In 1984, the results of an epidemiological study of ventriculostomy-related infection were published. One of the conclusions of the paper was that the incidence of ventriculostomy-related infections rose after 5 days of monitoring. This led to the recommendation that catheters be prophylactically changed at 5-day intervals if prolonged monitoring was required. A recent randomized prospective study on central venous catheters showed no reduction in infection with prophylactic catheter exchanges. This has led the authors to reexamine their experience with ventriculostomy infections. Data on 584 severely head injured patients with ventriculostomies were prospectively collected in two data banks, The Traumatic Coma Data Bank and The Medical College of Virginia Neurocore Data Bank. These data were retrospectively analyzed for factors associated with ventriculostomy related infections. It was found that there is a relationship of ventriculitis to monitoring duration but it is not simple or linear. There is a rising risk of infection over the first 10 days, but infection then becomes very unlikely despite a population that continues to be at risk. Patients in whom catheters were replaced prior to 5 days did not have a lower infection rate than those whose catheters were exchanged at more than 5-day intervals. Based on these data, it is recommended that ventriculostomy catheters for intracranial pressure monitoring be removed as quickly as possible, and in circumstances in which prolonged monitoring is required, there appears to be no benefit from catheter exchange.

Adolescent↗

Metabotropic glutamate receptor modulation of voltage-gated Ca2+ channels involves multiple receptor subtypes in cortical neurons.

Metabotropic glutamate receptor (mGluR) modulation of voltage-gated Ca2+ channels was examined in isolated deep layer frontoparietal cortical neurons under conditions designed to isolate calcium-independent modulatory pathways. Trans-1-aminocyclopentane-1,3-dicarboxylate (t-ACPD), a nonspecific mGluR agonist, produced rapid and reversible inhibition of Ca2+ channels. This effect was mimicked by agonists for group I and group II, but not group III, mGluRs. Effects of group I and II agonists often were observed in the same neurons, but separate subgroups of neurons were unresponsive to the group I agonist quisqualate or the group II agonist 2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV). Inhibition by quisqualate and DCG-IV was nonocclusive in neurons responding to both agonists. These agonists thus appear to act on different mGluRs. The mGluR antagonist alpha-methyl-4-carboxylphenylglycine attenuated inhibition by t-ACPD, quisqualate, and DCG-IV. Inhibition by quisqualate and DCG-IV was voltage-dependent. Although the effects of both agonists were greatly reduced by N-ethylmaleimide (NEM), inhibition by DCG-IV was more sensitive to NEM than inhibition by quisqualate. t-ACPD-induced inhibition was reduced by omega-conotoxin GVIA (omega-CgTx) and omega-agatoxin IVA (omega-AgTx) but was affected little by nifedipine. Inhibition by DCG-IV and quisqualate also was reduced by omega-CgTx. We conclude that multiple mGluR subtypes inhibit Ca2+ channels in cortical neurons and that N- and possibly P-type channels are inhibited. Modulation is via a rapid-onset, voltage-dependent mechanism that likely involves a pertussis toxin (PTX)-sensitive G-protein. Type I mGluRs may work via additional PTX-insensitive pathways.

Animals↗

[MR angiography and MR cholangiopancreatography].

MR angiography is an adjunctive for noninvasive evaluation of blood vessels and MR cholangiopancreatography is for bile duct and pancreatic duct. Clinical applications of MR angiography has been focused mainly on head and neck and its applications to the abdomen are still limited. However, this technique has the good potential for the evaluation of portal vein system. MR cholangiopancreatography can depict bile ducts and pancreatic duct simultaneously and three-dimensionally. This technique can evaluate the causes of the lesion and its extent noninvasively. In this article the practical uses of MR angiography and MR cholangiography in the abdomen are discussed.

Abdomen↗

Activation of adenosine A1 receptors initiates short-term synaptic depression in rat striatum.

High-frequency stimulation (HFS) of afferent fibers produced short-term depression (STD) and long-term depression (LTD) of corticostriatal synaptic transmission. Application of the non-selective adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) or the selective A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) blocked the induction of STD but not LTD. Application of adenosine or the selective A1 receptor agonist R(-)N6-(2-phenylisopropyl)adenosine (R-PIA) induced synaptic depression, while the A2a receptor agonist CGS 21680 did not consistently alter synaptic transmission. Depression induced by adenosine or R-PIA was not accompanied by changes in postsynaptic input resistance and appeared to involve a presynaptic depressant effect previously characterized at this synapse. These observations indicate that HFS leads to the production of endogenous adenosine that acts on presynaptic A1 receptors to initiate STD at corticostriatal synapses. Initiation and maintenance of LTD appear to be independent of A1 receptor activation.

Adenosine↗

Identification of efficient pentapeptide substrates for the tyrosine kinase pp60c-src.

The development of inhibitors of protein tyrosine kinases (PTKs) is a promising approach to obtaining new therapeutic agents for a variety of diseases, particularly cancer. However, the discovery of peptide-based inhibitors has been hindered by the lack of small peptide substrate sequences (i.e. five residues or less) with which a variety of inhibitor designs could be readily evaluated by replacing the Tyr with natural and unnatural amino acids. These prototypical small peptide inhibitors could then form the basis for designing analogous conformationally constrained, peptide-mimetic or non-peptide inhibitors with improved therapeutic potential. In this study we have identified the best known small peptide substrate for the PTK pp60c-src, which is the parent of the src family of nonreceptor PTKs. This pentapeptide substrate, Ac-Ile-Tyr-Gly-Glu-Phe-NH2, has a Km of 368 microM and Vmax of 1.02 mumol/min/mg when tested utilizing the assay methodology of Budde et al. (Anal. Biochem. 1992, 200, 347-351) after a series of modifications were made to more closely simulate the conditions inside a typical mammalian cell. This substrate was designed from information obtained by Songyang et al. (Nature 1995, 373, 536-539) with a 2.5 billion member combinatorial library of peptide substrates for pp60c-src. A second pentapeptide substrate, Ac-Glu-Asp-Ala-Ile-Tyr-NH2, with a weaker binding affinity (Km = 880 microM) but improved Vmax (1.86 mumol/min/mg), was also identified. This peptide was designed from the pp60c-src autophosphorylation sequence and information obtained by Songyang et al. (Ibid.) and Till et al. (J. Biol. Chem. 1994, 269, 7423-7428) with combinatorial libraries of peptide substrates. These new substrates provide sufficient binding affinities and rates of phosphorylation to be utilized for evaluating the relative effectiveness of various reversible and mechanism-based irreversible inhibitor designs for pp60c-src while appended to easily prepared small peptides.

Adenosine Diphosphate↗

Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin.

Lactacystin is a Streptomyces metabolite that inhibits cell cycle progression and induces neurite outgrowth in a murine neuroblastoma cell line. Tritium-labeled lactacystin was used to identify the 20S proteasome as its specific cellular target. Three distinct peptidase activities of this enzyme complex (trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing activities) were inhibited by lactacystin, the first two irreversibly and all at different rates. None of five other proteases were inhibited, and the ability of lactacystin analogs to inhibit cell cycle progression and induce neurite outgrowth correlated with their ability to inhibit the proteasome. Lactacystin appears to modify covalently the highly conserved amino-terminal threonine of the mammalian proteasome subunit X (also called MB1), a close homolog of the LMP7 proteasome subunit encoded by the major histocompatibility complex. This threonine residue may therefore have a catalytic role, and subunit X/MB1 may be a core component of an amino-terminal-threonine protease activity of the proteasome.

Acetylcysteine↗

A potential role for interferon-alpha in the pathogenesis of HIV-associated dementia.

Previous studies in patients receiving interferon-alpha (IFN-alpha) therapy and patients with systemic lupus erythematosus have demonstrated that elevated cerebrospinal fluid (CSF) levels of IFN-alpha are associated with cognitive dysfunction. We measured IFN-alpha levels in CSF and blood by ELISA in human immunodeficiency virus (HIV)-positive patients with (n = 21) and without (n = 23) dementia and HIV-negative controls (n = 48). IFN-alpha was significantly elevated in the CSF of HIV-positive patients with dementia compared to those without dementia and controls. An increasing amount of IFN-alpha in the CSF was correlated with the clinical parameter of increasing Memorial Sloan Kettering scores; although these correlations were not statistically significant, they further suggest an association of increased CSF IFN-alpha with neurocognitive dysfunction in AIDS. Immunocytochemical staining of brains demonstrated IFN-alpha-positive macrophages and astrocytes in frontal cortex and white matter and IFN-alpha mRNA was detected by reverse transcriptase-polymerase chain reaction, further indicating that IFN-alpha is made by cells within the brain and suggesting that the significant increases of IFN-alpha protein found in the CSF of patients with HIV-associated dementia complex are derived from intrinsic brain cells such as macrophages and astrocytes. Increased local production of IFN-alpha during HIV infection may contribute directly or indirectly to the pathogenesis of HIV-associated dementia.

AIDS Dementia Complex↗

Cross-task cross talk in memory and perception.

The application of the additive factors method depends on finding factors that selectively influence processing stages. When all the processes for a task are in series, a factor directly influencing a process might change its output and thereby have indirect influence on succeeding processes. We investigate whether such indirect influence is possible between processes associated with different tasks being performed together. In two dual-task memory scanning and arithmetic experiments with digits as the stimuli for both tasks, information relevant for only one of the tasks nonetheless affected performance of the other. When the same digit was relevant for the two tasks, cross-task facilitation and interference were observed in some cases. Displaying the same digit for both tasks led to relatively fast response times, paralleling the effect of flankers in the response competition paradigm. But repetition of digits in memory slowed responses. It is suggested that the need for control processes to keep task information segregated is responsible for the pattern of effects.

Adult↗

Interaction of cytochrome c with cardiolipin: an infrared spectroscopic study.

The interactions of cytochrome c (cyt c) with cardiolipin, a major anionic phospholipid of mitochondrial membranes, and dioleoylphosphatidylglycerol (DOPG), have been compared by infrared (IR) spectroscopy. The Fourier self-deconvoluted IR spectra of the lipid carbonyl groups indicate that both cyt c3+ and cyt c2+ perturb and/or dehydrate the interfacial region of cardiolipin bilayers. Only a slight perturbation, if any, is observed in the interfacial region of DOPG bilayers. However, the phosphate head region of DOPG is perturbed by cyt c3+, which was not detected in cardiolipin. The results suggest that cytochrome c in both redox states can partially penetrate into cardiolipin but not into DOPG bilayers. The interaction of cyt c with cardiolipin and DOPG is mainly hydrophobic and electrostatic, respectively. The Fourier self-deconvoluted IR spectra in the amide I region reveal that ca. 10% of the cyt c3+ alpha-helix unfolds to random coil upon binding to cardiolipin bilayers. However, only very slight secondary structural changes, if any, were detected when cyt c3+ binds to DOPG bilayers.

Amides↗

Regulation of enzymatic activity involved in sex pheromone production in the housefly, Musca domestica.

Ovarian produced ecdysteroids regulate sex pheromone production in the female housefly, inducing the synthesis of (Z)-9-tricosene (Z9-23:Hy), cis-9,10-epoxytricosane, (Z)-14-tricosen-10-one and methylalkanes. Experiments were performed to gain a detailed understanding of the processes affected by 20-hydroxyecdysone (20-HE) that result in sex pheromone production as the female becomes reproductively mature. A novel microsomal fatty acid synthetase (FAS) is present in the epidermal tissue and plays a role in producing the methyl-branched fatty acid precursors to the methylalkanes. This FAS is released from the microsomes in the presence of 3 M KCl. A major enzyme activity influenced by 20-HE is the fatty acyl-CoA elongation system. A shift in the chain length specificity of the products of the elongation system causes the change in the chain lengths of the alkenes produced to switch from C27 and longer in the previtellogenic female to C23 in the mature female. Data is presented indicating that it is the condensation activity of the elongation system that is affected. Z9-23:Hy arises from a 24 carbon acyl group which is reduced to an aldehyde, and then converted to the hydrocarbon. Data is presented demonstrating that it is the fatty acyl-CoA derivative and not the free fatty acid that is the substrate. There does not appear to be a chain length specificity which regulates the conversion of fatty acyl-CoAs to hydrocarbons as both 24 and 28 carbon fatty acyl-CoAs are converted to hydrocarbon by both males and females of all ages.

Acyl Coenzyme A↗

Early acquisition of verbs in Korean: a cross-linguistic study.

This cross-linguistic study investigates children's early lexical development in English and Korean, and compares caregivers' linguistic input in the two languages. In Study 1, the lexical development of nine Korean children was followed from 1;2 to 1;10 by monthly visits and maternal reports. These Korean data were compared to previously collected English longitudinal data. We find that: (1) Korean children as young as 1;3 use verbs productively with appropriate inflections. (2) Seven of the nine children show a verb spurt at around 1;7; for six of these children the verb spurt occurs before the noun spurt. No such early verb spurt is found in the English data. Unlike in English, both verbs and nouns in Korean are dominant categories from the single-word stage. (3) Korean children express language-specific distinctions of locative actions with verbs. Study 2, a crosslinguistic study of caregivers' input in English and Korean, shows that Korean mothers provide more action verbs but fewer object nouns than American mothers. Also, Korean mothers engage in activity-oriented discourse significantly more than American mothers. Our study suggests that verbs are accessible to children from the beginning, and that they may be acquired early in children who are encouraged to do so by their language-specific grammar and input.

Child Language↗

Fluorescent in situ hybridization of a bacterial artificial chromosome.

Fluorescent in situ hybridization (FISH) of a 130 kilobase cotton (Gossypium hirsuitum L.) bacterial artificial chromosome (BAC) clone containing a high proportion of single-copy DNA produced a large pair of FISH signals on the distal end of the long arm of a pair of chromosomes of the D-genome species G. raimondii Ulbr. and produced a fainter pair of signals on a small submetacentric pair of chromosomes of the A-genome species G. herbaceum L. The signals were synthetic with a nucleolar organizer region in G. raimondii and G. herbaceum. Signal pairs were easily recognized in interphase and metaphase cells either with or without suppression of repetitive sequences with unlabeled G. hirsutum C0t-1 DNA. High quality FISH results were consistently obtained and image analysis was not required for viewing or photography. Results indicate that FISH of BAC clones is an excellent tool for the establishment of new molecular cytogenetic markers in plants and will likely prove instrumental in the development of useful physical maps for many economically important crop species.

Bacteria↗

The incidence of drug resistant tuberculosis in 1279 Korean patients.

OBJECTIVES: In the past decade, the incidence of tuberculosis has been decreased in Korea and the nationwide survey of tuberculosis from 1965 through 1990 suggested a declining tendency of resistant organisms. But the prevalence rate of multidrug resistance of Mycobacterium tuberculosis is still a serious problem in Korea, and the aim of this study is to check the drug resistance pattern in the patients visiting University Hospital, the 3rd referral center. METHODS: We reviewed 1279 cases (522 female, 757 male, mean age 39.4 +/- 16.7) of bacteriologically proven tuberculosis seen during the period from 1986 to 1992 retrospectively. Of 1093 patients, who were indentified in previous medical history, 454 (41.5%) had a history of prior antituberculous chemotherapy. RESULTS: Resistance rate (resistant to 1 or more drugs) was 33.9%. Eleven percent of patients had resistance to a single drug (INH: 80.6%). Twenty two percent of patients had resistance to 2 or more drugs. Resistance rate is higher (47.4%) in the patients with a history of prior treatment than without a history (25.5%). CONCLUSIONS: These data suggest that the high rate of multidrug resistance in Korea did not show any decreasing tendency. So, mycobacterial culture and sensitivity tests should be recommended at initial treatment of tuberculosis and potent antituberculosis drugs are strongly recommended.

Adult↗

Cytokine mRNA expression in postischemic/reperfused myocardium.

While the role of cytokines in mediating injury during hind limb skeletal muscle ischemia followed by reperfusion has recently been described, the role of cytokines in myocardial infarction and ischemia/reperfusion have remained relatively unexplored. We hypothesize that cytokines play an important role in the regulation of postischemic myocardial inflammation. This study reports the temporal sequence of proinflammatory cytokine gene expression in postischemic/reperfused myocardium and localizes interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha)-protein by immunostaining. Rats were subjected to either permanent left anterior descending (LAD) occlusion or to 35 minutes of LAD occlusion followed by reperfusion and sacrificed up to 7 days later. Rat-specific oligonucleotide probes were used to semiquantitatively assess the relative expression of mRNA for TNF-alpha, IL-1 beta, IL-2, IL-6, interferon-gamma (IFN-gamma), and transforming growth factor-beta 1 (TGF-beta 1) utilizing the reverse transcriptase-polymerase chain reaction amplification technique. Increased cardiac mRNA levels for all cytokines except IL-6 and IFN-gamma were measurable within 15 to 30 minutes of LAD occlusion and increased levels were generally sustained for 3 hours. During early reperfusion, mRNA levels for IL-6 and TGF-beta 1 were significantly reduced compared with permanent LAD occlusion. In both groups, cytokine mRNA levels all returned to baseline levels at 24 hours, while IL-1 beta, TNF-alpha, and TGF-beta 1 mRNA levels again rose significantly at 7 days only in animals with permanent LAD occlusion. Immunostaining for IL-1 beta and TNF-alpha protein revealed two patterns of reactivity: 1) microvascular staining for both IL-1 beta and TNF-alpha protein only in postischemic reperfused myocardium in early post-reperfusion time points; and 2) staining of infiltrating macrophages in healing infarct zones which was most prominent at 7 days after permanent LAD occlusion. These results provide evidence for local expression of cytokine mRNA in postischemic myocardium and suggest that regulation of local cytokine release is altered during the postischemic period.

Animals↗

Unusual mechanism of hydrocarbon formation in the housefly: cytochrome P450 converts aldehyde to the sex pheromone component (Z)-9-tricosene and CO2.

An unusual mechanism for hydrocarbon biosynthesis is proposed from work examining the formation of (Z)-9-tricosene (Z9-23:Hy), the major sex pheromone component of the female housefly, Musca domestica. Incubation of (Z)-15-[1-14C]- and (Z)-15-[15,16-3H2]tetracosenoic acid (24:1 fatty acid) with microsomes from houseflies gave equal amounts of [3H]Z9-23:Hy and 14CO2. The formation of CO2 and not CO, as reported for hydrocarbon formation in plants, animals, and microorganisms [Dennis, M. & Kolattukudy, P. E. (1992) Proc. Natl. Acad. Sci. USA 89, 5306-5310], was verified by trapping agents and by radio-GLC analysis. Incubation of (Z)-15-[15,16-3H2]tetracosenoyl-CoA with microsomal preparations in the presence of NADPH and O2 gave almost equal amounts of (Z)-15-3H2]tetrasosenal (24:1 aldehyde) and Z9-23:Hy. Addition of increasing amounts of hydroxylamine (aldehyde trapping agent) caused a decrease in hydrocarbon formation with a concomitant increase in oxime (aldehyde derivative) formation. The 24:1 aldehyde was efficiently converted to (Z)-9-tricosene only in the presence of both NADPH and O2. Bubbling carbon monoxide (20:80 CO/O2) or including an antibody against housefly cytochrome P450 reductase inhibited the formation Z9-23:Hy from 24:1 aldehyde. These data demonstrate an unusual mechanism for hydrocarbon formation in insects in which the acyl-CoA is reduced to the corresponding aldehyde and then carbon-1 is removed as CO2. The requirement for NADPH and O2 and the inhibition by CO and the antibody to cytochrome P450 reductase strongly implicate the participation of a cytochrome P450 in this reaction.

Aldehydes↗

Intracerebral cytokine mRNA expression during fatal and nonfatal alphavirus encephalitis suggests a predominant type 2 T cell response.

Sindbis virus (SV) causes an acute encephalomyelitis in mice. A T cell-dependent inflammatory response is first detected 3 days after infection and includes T cells, B cells, and macrophages. The cytokines produced locally by intrinsic cells of the brain in response to infection and by infiltrating mononuclear cells and their contributions to outcome of infection have not been identified. Semiquantitative reverse transcriptase-PCR was used to evaluate the expression of mRNAs for IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, leukemia inhibitory factor (LIF), and TGF-beta in the brain during fatal and nonfatal SV encephalitis of immunocompetent BALB/cJ and immunodeficient scid/CB17 mice. IL-1 beta and IL-6 mRNAs were detected in uninfected mice before infection and were up-regulated within 24 h. TGF-beta mRNA was also constitutively expressed in uninfected mice. LIF mRNA was occasionally detected in uninfected mice but increased in amounts only in BALB/cJ not scid mice after infection. TNF-alpha, IL-4, and IL-10 mRNAs were not found in uninfected mice but were induced within 24 h and continued to rise through 7 days after infection with substantially higher levels in BALB/cJ than scid mice. These data suggest that intrinsic brain cells produce IL-1, IL-4, IL-6, IL-10, LIF, and TGF-beta mRNAs in response to viral infection. IFN-gamma and IL-2 mRNAs were detected only in BALB/cJ mice and not until 3 days after infection with the initiation of inflammation. IL-4 and IL-10 mRNAs were more persistent and more easily detectable than IL-2 and IFN-gamma mRNAs. These data suggest a predominant type 2 cytokine response in the brain during SV encephalitis. BALB/cJ mice infected with a neurovirulent strain of SV (NSV), had 100% mortality, whereas NSV-infected scid mice developed persistent nonfatal infection. Inflammation was more intense in NSV-infected mice, however, no substantial differences in cytokine mRNA levels were detected when compared with mice with nonfatal SV infection suggesting that the cytokines measured do not in and of themselves lead to fatal central nervous system disease.

Alphavirus Infections↗

Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains.

The amount of messenger RNA encoding human inducible nitric oxide synthase and the presence and distribution of NADPH diaphorase were determined in tissue sections from multiple sclerosis (MS) and control brains. Levels of human nitric oxide synthase messenger RNA were markedly elevated in MS brains when compared to normal control brains. NADPH diaphorase activity, a histochemical stain reflecting nitric oxide synthase catalytic activity, was detected in reactive astrocytes in active demyelinating MS lesions and at the edge of chronic active demyelinating lesions. Control brains did not contain NADPH diaphorase-positive astrocytes. These results implicate the free radical nitric oxide in the pathogenesis of demyelinating MS lesions.

Adult↗