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S Nakashima

Publications and source records attributed to S Nakashima.

At least 145 records · Page 8Linked to original sources
PubMed1996

Differential mRNA expression of phospholipase D (PLD) isozymes during cAMP-induced differentiation in C6 glioma cells.

GTP gamma S-dependent phospholipase D (PLD) activity time-dependently increased during differentiation of rat C6 glioma cells to astrocytic phenotypes induced by dibutyryl cyclic AMP (dbcAMP)/theophylline. The changes in PLD mRNA level were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) method using the degenerate primers designed based on two conserved amino acid sequences in PLDs of human and yeast. The amplified three DNA fragments (tentatively termed as rPLDa, b, and c) contained the conserved regions present in PLDs of various organisms. RT-PCR using non-degenerate primers showed that rPLDa mRNA increased within 12h following treatment with dbcAMP, reaching a broad plateau and then returned to the initial level at 48h. In contrast, the level of rPLDb mRNA showed a concurrent decrease. rPLDc decreased in a time-dependent manner. These results suggest that the expression of PLD mRNAs are differentially regulated during differentiation in C6 glioma cells.

Amino Acid Sequence↗
PubMed1996

Effect of Clostridium difficile toxin B on IgE receptor-mediated signal transduction in rat basophilic leukemia cells: inhibition of phospholipase D activation.

Antigen (Ag)-stimulated phospholipase D (PLD) activation and secretion were almost abolished by pretreatment of rat basophilic leukemia (RBL)-2H3 cells for 4 h with 5 ng/ml Clostridium difficile Toxin B which is known to inhibit Rho family proteins (Rho, Cdc42, Rac). The concentration-dependent inhibition of PLD activation was well correlated with the level of glucosylation of Rho family proteins. In streptolysin O-permeabilized RBL cells, Toxin B suppressed [3H] phosphatidylbutanol (PBut) formation in response to guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and phorbol 12-myristate 13-acetate (PMA) by 67 and 43%, respectively. The synergistic PLD activation by GTP gamma S and PMA was also reduced by Toxin B by 67%. These results suggest that the IgE receptor-coupled PLD activation is largely mediated by Rho proteins.

Animals↗
PubMed1996

Molecular cloning of delta 9 fatty acid desaturase from the protozoan Tetrahymena thermophila and its mRNA expression during thermal membrane adaptation.

In response to a decrease in its growth temperature, the protozoan Tetrahymena is known to increase the level of unsaturated fatty acids in its membrane phospholipids so as to maintain the correct physical state (fluidity) of the membranes. In this organism, synthesis of unsaturated fatty acids is initiated by delta 9 acyl-CoA desaturase. Our previous studies have shown that, during cold adaptation, the activity of microsomal palmitoyl- and stearoyl-CoA desaturase increases, reaching a maximal level at 2 h after a temperature down-shift to 15 degrees C. Two hypotheses have been proposed to explain this increase in desaturase activity: (1) self-regulation via a direct effect of reduced membrane fluidity, and (2) induction of desaturase mRNA. However, the precise mechanism is not clearly understood. In order to obtain further insight into the mechanism of regulation of the desaturase, we have isolated a gene that encodes delta 9 fatty acid desaturase from T. thermophila and examined its expression during cold adaptation. The nucleotide sequence indicates that the 1.4 kbp gene encodes a polypeptide of 292 amino acid residues which shows marked sequence similarity to delta 9 acyl-CoA desaturases from other sources, e.g. rat, mouse, Amblyomma americanum and Saccharomyces cerevisiae. This protein has three histidine-cluster motifs (one HXXXXH and two HXXHH), and two hydrophobic regions which are conserved among delta 9 acyl-CoA desaturases. The level of desaturase mRNA was sensitive to decreasing the temperature of the culture media, and was close to maximal immediately after the temperature was shifted down from 35 degrees C to 15 degrees C (0.8 degrees C/min). Thereafter, the amount of mRNA gradually decreased with time, but remained above the control level for at least 5 h. Furthermore, during the course of the cooling process to 15 degrees C, the increased expression of desaturase mRNA became evident at 27 degrees C. Nuclear run-on analysis and actinomycin D chase experiments revealed that the elevation of the mRNA level was due to increases in both transcription and mRNA stability. These results suggest that the enhanced desaturase activity is controlled, at least in part, at the transcriptional level.

Adaptation, Physiological↗
PubMed1996

Differential translocation of phospholipase C isozymes to integrin-mediated cytoskeletal complexes in thrombin-stimulated human platelets.

To investigate a role of phospholipase C (PLC) isozymes in the integrin alphaIIbbeta3-mediated signaling, their location was examined in thrombin-activated human platelets, revealing different regulation of their translocation to the cytoskeleton (CSK). In resting platelets, the major PLCs such as PLCbeta2, PLCbeta3a (155 kDa), and PLCgamma2 and the minor PLCs (PLCbeta1 and PLCgamma1) were located in the Triton X-100-soluble (Tx.Sol) fraction and the membrane skeleton, whereas PLCbeta3b (140 kDa) was present only in Tx.Sol fraction when examined by Western immunoblotting. Thrombin stimulation caused a rapid and transient translocation of PLCbeta3a and PLCbeta3b and a slower accumulation of PLCbeta2 and PLCgamma2 in the reorganized CSK. The translocation to CSK of both PLCbeta3a and PLCbeta3b, but not PLCbeta2, was dependent on integrin alphaIIbbeta3-mediated aggregation. Furthermore, an actin polymerization inhibitor, cytochalasin D, or a protein tyrosine kinase inhibitor, genistein, abolished the CSK association of alphaIIbbeta3, PLCbeta3a, and PLCbeta3b. In the genistein-pretreated platelets, pp60(c-)src, Gq, and protein kinase Calpha were no longer able to associate with CSK. In contrast, these agents had no or marginal inhibitory effects on the CSK association of PLCbeta2 and Gi2. The late diacylglycerol generation induced by thrombin stimulation was significantly reduced by the genistein treatment. These results suggest that the integrin alphaIIbbeta3-mediated cytoskeletal association of PLCbeta3 is regulated by protein tyrosine kinase and also that the activation of the relocated PLC may play a role in the late platelet-to-platelet aggregation in thrombin-stimulated human platelets.

Actins↗
PubMed1996

Suppressed expression of CD44 variant isoforms during human glioma A172 cell differentiation induced by cyclic AMP.

CD44 is a major receptor for hyaluronic acid, which is the most frequent route of malignant glioma invasion. Multiple isoforms of CD44 are generated by alternative mRNA splicing. We have examined differential expression of CD44 variant isoforms (CD44vs) during dibutyryl cyclic AMP (dbcAMP)/theophylline-induced differentiation of human glioma A172 cells using reverse transcriptase-polymerase chain reaction (RT-PCR). Treatment of cells with dbcAMP and theophylline caused decreased expression of all CD44 isoforms after 24 h. The CD44 standard form was observed to return to the unstimulated level after 72 h, whereas the variant isoforms, CD44 8v-10v and 10v, remained at the low level after 24-72 h. Changes of CD44vs were correlated with the level of expression of c-jun. These results suggested that the expression patterns of CD44vs might correlate with cellular differentiation in human glioma cells.).

Brain Neoplasms↗
PubMed1996

Regulation of membrane-bound phospholipase D by protein kinase C in HL60 cells. Synergistic action of small GTP-binding protein RhoA.

In HL60 cells, the membrane-bound phospholipase D (PLD) was stimulated by 4beta-phorbol 12-myristate 13-acetate (PMA) in the presence of the cytosolic fraction from HL60 cells or rat brain. The cytosolic factor for this PMA-induced PLD activation was subjected to purification from rat brain by sequential chromatographies. The PLD stimulating activity was found in protein kinase C (PKC) fraction containing alpha, betaI, betaII, and gamma isozymes. PKC isozymes were further separated by hydroxylapatite chromatography. PKCalpha and - beta, but not gamma, isozymes were found to activate membrane-bound PLD. PKCalpha was much more effective than PKCbeta for PLD activation. Millimolar concentrations of MgATP were required for the PKC-mediated PLD activation in HL60 membranes. MgATP is utilized to maintain the levels of phosphatidylinositol 4,5-bisphosphate (PIP2) under these assay conditions. The PKC-mediated PLD activation was completely inhibited by neomycin, a high affinity ligand for PIP2, and this suppression was recovered by the addition of exogenous PIP2. Thus, these results suggest that PIP2 is supposed to play a key role in PKC-mediated PLD activity in HL60 membranes. Furthermore, PKCalpha-mediated PLD activation was potentiated by the addition of recombinant RhoA protein in the presence of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). The results obtained here indicate that PKCalpha and RhoA (GTP form) exert a synergistic action in the membrane-bound PLD activation in HL60 cells.

Animals↗
PubMed1996

Ceramide inhibits IgE-mediated activation of phospholipase D, but not of phospholipase C, in rat basophilic leukemia (RBL-2H3) cells.

Ceramide, a product of sphingomyelin hydrolysis by sphingomyelinase, elicits various cellular functions and has recently been regarded as a second messenger. To investigate the role of ceramide in rat basophilic leukemia (RBL-2H3) cells, the effects of a cell-permeable analogue, N-acetylsphingosine (C2-ceramide), on Ag-mediated cellular responses were examined. C2-Ceramide inhibited Ag- or PMA-induced activation of phospholipase D (PLD), whereas Ca2+ ionophore A23187-induced PLD activation was not affected. C2-Ceramide failed to inhibit PLD activity in two different in vitro assay systems. Since PLD activity is known to be regulated by several factors, the effects of C2-ceramide on these factors were examined. We have previously reported the possible involvement of protein tyrosine kinase in Ag-mediated PLD activation. However, C2-ceramide had no effect on Ag-induced protein tyrosine phosphorylation, including mitogen-activated protein (MAP) kinases. In fura-2-loaded RBL-2H3 cells, C2-ceramide suppressed Ag-induced Ca2+ influx, leaving initial Ca2+ increase and inositol phosphate production unaffected. Western blot analysis revealed that Ag caused translocation of protein kinase C (PKC) alpha, beta 1, beta 2, delta and epsilon isozymes from cytosol to membrane fraction. Translocation of alpha, beta 1, and beta 2 isozymes was specifically prevented by C2-ceramide. Moreover, C2-ceramide suppressed Ag-induced serotonin release. In the absence of extracellular Ca2+, Ag-induced PLD activation and release reaction were greatly reduced. The inhibitory profile was nearly the same as that obtained in C2-ceramide-treated cells. These results suggest that C2-ceramide inhibits Ag-induced PLD activation and serotonin release, probably through the blockage of Ca2+ influx and translocation of Ca(2+)-dependent PKC isozymes in RBL-2H3 cells.

Animals↗
PubMed1996

PLD activation in Chinese hamster ovary (CHO) cells transfected with PGF2 alpha receptor cDNA.

Pertussis toxin-insensitive GTP-binding protein was observed to be involved in prostaglandin F2 alpha (PGF2 alpha)-induced phosphoinositide metabolism in Chinese hamster ovary (CHO) cells transfected with PGF2 alpha receptor cDNA (CHO-PGF2 alpha R cells) (Ito, S. et al. Biochem. Biophys. Res. Commun. 200: 756,1994). In the present study, we investigated PGF2 alpha-induced PLD activation in CHO-PGF2 alpha R cells. PLD activation was examined by measuring the production of [3H]phosphatidylbutanol ([3H]PBut), a specific product of the PLD-catalyzed transphosphatidylation reaction. PGF2 alpha-induced [3H]PBut formation was concentration-dependent with the maximal level obtained at 1 microM PGF2 alpha. The maximal [3H]PBut formation was observed at 2 min after addition of PGF2 alpha. Depletion of extracellular Ca2+ with EGTA suppressed PGF2 alpha-induced PLD activation by 50%. PKC inhibitors Ro31-8425 and calphostin C inhibited PGF2 alpha-induced [3H]PBut formation by 50%. PTK inhibitors genistein and herbimycin A failed to inhibit PGF2 alpha-induced PLD activation. A combination of maximal effective concentrations of PGF2 alpha (1 microM) and PMA (100 nM) enhanced PLD activation in an additive manner. Pretreatment of the cells with PMA for 2 h down-regulated PKC alpha and decreased PGF2 alpha-induced PLD activation. These results suggest that PLD activation by PGF2 alpha is mediated by both PKC-dependent and -independent pathways and that PKC alpha is involved in the former pathway.

Animals↗
PubMed1996

Membrane-associated phospholipase D activity in neural cell line PC12.

Stimulation of PC12 cells with carbachol (Cch) or phorbol 12-myristate 13-acetate (PMA) induced [3H]phosphatidylbutanol (PBut) production. Depletion of extracellular Ca2+ abolished the Cch-mediated phospholipase D (PLD) activation, indicating the requirement of Ca2+ influx. Two different types of PLD activity, oleate-dependent and GTP gamma S-dependent, were examined by using exogenous [3H]phosphatidylcholine substrate. PLD activity of the membrane fraction of PC12 cells was highly dependent on oleate and independent of GTP gamma S. This profile is in sharp contrast to that observed in HL60 cells showing the profound GTP gamma S-induced activation of PLD. The oleate-dependent PLD activity of PC12 membrane was inhibited by high concentrations of Ca2+ and Mg2+. These results indicate that Ca2+ may not directly activate PLD but through some Ca(2+)-dependent mechanism(s) in Cch-stimulated cells.

Animals↗
PubMed1996

Brefeldin A inhibits antigen- or calcium ionophore-mediated but not PMA-induced phospholipase D activation in rat basophilic leukemia (RBL-2H3) cells.

Recent reports have indicated that ADP-ribosylation factor (ARF) plays a role in the regulation of phospholipase D (PLD) activity in the in vitro assay system. Since a fungal metabolite brefeldin A (BFA) is known to interfere with ARF function, the effect of BFA on antigen-induced PLD activation was examined in rat basophilic leukemia (RBL-2H3) cells. BFA inhibited the antigen-induced formation of phosphatidylbutanol (PBut), a specific and stable metabolite produced by PLD activity in a concentration-dependent manner. The maximal inhibition obtained at 10 micrograms/ml of the drug was nearly 70% and further inhibition was not observed at higher concentrations. Ca(2+)-ionophore A23187-mediated PLD activation was also prevented by BFA. In contrast, BFA failed to inhibit PLD activation in response to 4 beta-phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC). This indicates that there are BFA-sensitive and BFA-insensitive pathways leading to PLD activation in RBL-2H3 cells and also that the PKC-mediated pathway may be insensitive to BFA treatment, suggesting the existence of PLD isozymes. BFA inhibited Ag-induced serotonin release at a concentration 20-fold lower than that needed for the inhibition of PLD. Moreover, PMA caused a marked production of PBut, but it failed to elicit secretory response. This implies that PLD may be not a crucial element for secretory responses.

Animals↗
PubMed1996

Phenylarsine oxide (PAO)-mediated activation of phospholipase D in rat basophilic leukemia (RBL-2H3) cells: possible involvement of calcium and protein kinase C.

Addition of phenylarsine oxide (PAO) to [3H]oleic acid-labeled rat basophilic leukemia (RBL-2H3) cells gave rise to the remarkable formation of [3H]phosphatidylbutanol (PBut), a specific product of phospholipase D (PLD) activation. Preincubation of cells with 2,3-dimercaptopropanol (DMP) or dithiothreitol (DTT), compounds containing sulfhydryls, prevented PAO-stimulated [3H]PBut formation, indicating that PAO-stimulated PLD through interacting with vicinal thiol groups. Treatment of cells with PAO resulted in increase in intracellular Ca2+ concentration without significant production of inositol phosphates. Removal of extracellular free Ca2+ by chelating with EGTA was found to inhibit [3H]PBut formation by PAO. Incubation of cells with 20 nM phorbol 12-myristate 13-acetate (PMA) for 6 h caused down-regulation of protein kinase C (PKC) alpha and beta isozymes, whereas it had no effect on PKC delta, epsilon and zeta isozymes. Under this condition, decrease in PAO-stimulated [3H]PBut formation was observed to occur with a concomitant decrease in the level of PKC alpha and beta isozymes. These results suggest that a covalent bridge between vicinal thiol groups of cell surface proteins induced by PAO potentiates PLD activation and that PAO-induced PLD activation is regulated by Ca2+ and PKC alpha and/or beta isozymes.

Animals↗
PubMed1996

Mitogen-activated protein kinase activation in hepatocyte growth factor-stimulated rat hepatocytes: involvement of protein tyrosine kinase and protein kinase C.

Hepatocyte growth factor (HGF) stimulated mitogen-activated protein (MAP) kinases and MAP kinase kinase in primary cultured rat hepatocytes. Inhibitors for protein kinase C (PKC), Ro31-8425, H-7, and calphostin C, reduced HGF-induced MAP kinase activity. A PKC activator, phorbol myristate acetate (PMA), induced MAP kinase activation in a concentration-dependent manner. Protein tyrosine kinase (PTK) inhibitors, genistein, and ST638 also inhibited HGF-induced MAP kinase activation. Furthermore, HGF increased formation of Ras guanosine triphosphate (GTP) complex, indicating Ras activation. Genistein inhibited HGF-induced Ras activation, but Ro31-8425 was without effect. On the other hand, Ro31-8425 decreased HGF-induced [3H]arachidonic acid (AA) release and [3H]thymidine incorporation. Genistein also prevented [3H]AA release and [3H]-thymidine incorporation. Moreover, a commonly used phospholipase A2 (PLA2) inhibitor, quinacrine, decreased HGF-induced [3H]AA release and [3H]thymidine incorporation. The inhibitory profile of [3H]AA release was well correlated with that of [3H]thymidine incorporation in Ro31-8425-, genistein-, and quinacrine-treated cells. A cyclooxygenase inhibitor, indomethacin, which suppressed HGF-induced DNA synthesis, had minimal effect on MAP kinase activation. In contrast, prostaglandin (PG) E1, E2, or F2 alpha, which stimulate [3H]thymidine incorporation to the same level as that caused by HGF in hepatocytes, caused very weak activation of MAP kinases. These results suggest that PTK, Ras, and PKC play roles in MAP kinase activation induced by HGF and that MAP kinase activation resulting in AA release is involved in DNA synthesis in rat hepatocytes.

Animals↗
PubMed1996

Phospholipase D activation in hepatocyte growth factor-stimulated rat hepatocytes mediates the expressions of c-jun and c-fos: involvement of protein tyrosine kinase, protein kinase C, and Ca2+.

Hepatocyte growth factor (HGF) activated phospholipase D (PLD) in primary-cultured rat hepatocytes, as assessed by the formation of phosphatidylbutanol (PBut), a specific and stable product of PLD activity in the presence of 0.3% butanol. PLD hydrolyzes phosphatidylcholine to choline and phosphatidic acid (PA), which is further metabolized to diacylglycerol (DG) by PA phosphohydrolase (PAP). In HGF-stimulated hepatocytes, butanol prevented the formation of PA and DG. A PAP inhibitor, propranolol, inhibited DG production with a reciprocal increase of PA, implying that PLD played a role in the formation of not only PA but DG. Inhibitors for protein kinase C (PKC), Ro31-8425, H-7, and calphostin C, reduced HGF-induced PLD activation. A protein tyrosine kinase (PTK) inhibitor, genistein but not its inactive analogue daidzein, inhibited PLD activation by HGF. Moreover, depletion of extracellular Ca2+ by omission of Ca2+ or by chelating residual Ca2+ with ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) abolished HGF-induced PLD activation. HGF, phorbol myristate acetate (PMA) and a DG analog, oleylacetylglycerol (OAG), activated the expression of c-jun and c-fos messenger RNAs (mRNAs). Ro31-8425, calphostin C, and genistein, which prevented HGF-induced PLD activation, inhibited induction of these immediate early genes. Butanol and propranolol at concentrations which effectively inhibited the formation of DG, suppressed HGF-induced expression of c-jun and c-fos mRNAs. However, HGF-induced mitogen-activated protein kinase (MAPK) activation was not affected by both butanol and propranolol. These results suggest that PTK, PKC, and Ca2+ regulate HGF-induced PLD activation, and that DG produced by PLD pathway may play a role in the induction of immediate early genes, which is activated in MAPK-independent manner, in rat hepatocytes.

Animals↗
PubMed1996

Isolation and characterization of teichoic acid-lake substance as an adhesin of Staphylococcus aureus to HeLa cells.

A cell wall component that bound to HeLa cells (HeLa cell-binding CWC) was isolated from a clinical isolate of Staphylococcus aureus. The HeLa cell-binding CWC was resistant to heat (100 C, 1 hr) and proteases, did not stain with Coomassie Brilliant Blue R-250 on SDS-PAGE but stained as a broad band with antiserum against the strain on Western blots. These data suggest that the HeLa cell-binding CWC is not a protein, and may be teichoic acid. Purified teichoic acid bound to HeLa cells, whereas fractions without teichoic acid did not. In Western blots, HeLa cell-binding CWC appeared as a broad band of less than 35 kDa, similar to that of purified teichoic acid. These data suggest that the HeLa cell-binding CWC obtained in this study is teichoic acid. Teichoic acid inhibited S. aureus adherence to HeLa cells and bound to the cells time and dose dependently, in a saturable and reversible manner, and therefore appears to be an adhesin of S. aureus to HeLa cells.

Adhesins, Bacterial↗
PubMed1996

Efficacy and side effects of intermittent recombinant interferon-alpha 2a in chronic aggressive hepatitis C: with or without initial daily administration.

To investigate the therapeutic effect and incidence of side effects of recombinant interferon-alpha 2a (IFN-alpha) in chronic aggressive hepatitis C under stratification by administration mode, a study was conducted by assigning patients to either group A (daily consecutive administration of 9 million units (MU) IFN-alpha for 2 weeks and, thereafter, 3 MU intermittently 3 times weekly for 22 weeks) or group B (exclusively intermittent administration; 9 MU IFN-alpha twice weekly or 6 MU IFN-alpha thrice weekly for 24 weeks). The 28 patients in group A received IFN-alpha for 24 weeks up to a total dose of 324 MU and the 53 patients in group B received the same for 24 weeks up to a total dose of 432 MU. When recovery was defined as the absence of hepatitis C virus (HCV)-RNA 6 months after the completion of treatment, the rate of recovery for group A was 32.1% and that for group B was 37.7%, the latter being higher but without significance. Side effects in groups A and B consisted of leucopenia occupying 14.3 and 7.5%, respectively, and thrombocytopenia occupying 42.9 and 11.3%, respectively; group B exhibited lower values for both side effects. No difference was detected between these groups in other side effects, including pyrexia, generalized malaise, arthralgia or psilosis. Intermittent administration from the outset permitted shortened duration of hospitalization and earlier rehabilitation. Intermittent administration of INF-alpha is required when treating patients with chronic hepatitis C showing lower leucocyte or platelet counts.

Chronic Disease↗
PubMed1996

Clinico-epidemiological features of infantile hydrocephalus in Japan.

In 1988, a nationwide survey was conducted in Japan, in order to examine the prevalence and clinico-epidemiological features of hydrocephalus that developed before 1 year of age. The study was based on questionnaires that were sent to all hospitals in Japan with more than 200 beds. There were 1435 patients who were eligible for the analysis. They were born before 1987 and diagnosed as having infantile hydrocephalus. Approximately two-thirds of the patients had primary hydrocephalus. Neural tube defects were the most frequent cause of the primary hydrocephalus and common among full-term infants. On the other hand, secondary hydrocephalus occurred more often in preterm infants, mainly following intracranial hemorrhage. Intracranial hemorrhage as a cause of hydrocephalus increased over the year, while the incidence of hydrocephalus secondary to intracranial infection decreased during the same period.

Brain↗
PubMed1996

Cortical hypometabolism and delayed myelination in West syndrome.

PURPOSE: We examined the relation between cortical hypometabolism and delayed myelination in patients with West syndrome (WS). METHODS: Serial positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG) and magnetic resonance imaging (MRI) were performed in 18 patients with WS, first at the onset of epileptic spasms and later at age 10 months. The age at onset of seizures ranged from 2 to 7 months. Ten patients were diagnosed as having cryptogenic WS and 8 as having symptomatic WS. RESULTS: Cortical hypometabolism was detected in many patients at onset of epilepsy, but disappeared later, whereas delayed myelination tended to become evident with age. PET showed diffuse or focal cortical hypometabolism in 12 patients at onset, but in only 6 patients at age 10 months. MRI showed delayed myelination in only 2 patients at onset of epilepsy, but the number of patients with delayed myelination increased to 12 at age 10 months. Delayed myelination was more often present in patients with cortical hypometabolism. Delayed myelination was noted in 11 (85%) of 13 patients with cortical hypometabolism on first or second PET scans, but in only 1 (20%) of 5 patients who did not show PET abnormalities. Hypometabolism on the first or second PET scan was positively correlated with delayed myelination at age 10 months. CONCLUSIONS: In patients with WS, assessing myelination with MRI again at age 8-10 months is important even when MRI at the onset of epilepsy appears normal. Serial MRI and PET scans disclose more detailed pathophysiology of WS.

Age of Onset↗