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31.
We have developed a method for obtaining pneumococcal lipoteichoic acid (LTA) with none, one, or two acyl chains. Anion-exchange chromatography at pH 9.5 yields pneumococcal LTA (labeled LTA-9.5) that has a mass spectrum identical to that of pre-ion-exchange LTA and loses 500 mass units after deacylation by alkali hydrolysis. Anion exchange at pH 10.5 produces LTA (labeled LTA-10.5) with mass peaks that are 264 mass units lower than those of pre-ion-exchange LTA, and deacylation of LTA-10.5 by alkali hydrolysis reduces the mass by only 239 mass units. This result indicates that LTA-10.5 has lost one of the two acyl chains, whereas LTA-9.5 has both acyl chains. When the biological properties of LTA-9.5 and LTA-10.5 are examined with mouse cells, only LTA-9.5 (and not LTA-10.5) is able to stimulate mouse cells to produce tumor necrosis factor alpha, interleukin-1beta, and nitric oxide. In contrast, both LTA-9.5 and LTA-10.5 can stimulate human cells. LTA became inactive when both acyl chains were removed. Thus, acyl chains are critical for LTA function, and small variations in acyl chains can alter biological properties of LTA. 相似文献
32.
Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization 总被引:33,自引:0,他引:33 下载免费PDF全文
Ozaki H Seo MS Ozaki K Yamada H Yamada E Okamoto N Hofmann F Wood JM Campochiaro PA 《The American journal of pathology》2000,156(2):697-707
Retinal vasculogenesis and ischemic retinopathies provide good model systems for study of vascular development and neovascularization (NV), respectively. Vascular endothelial cell growth factor (VEGF) has been implicated in the pathogenesis of retinal vasculogenesis and in the development of retinal NV in ischemic retinopathies. However, insulin-like growth factor-I and possibly other growth factors also participate in the development of retinal NV and intraocular injections of VEGF antagonists only partially inhibit retinal NV. One possible conclusion from these studies is that it is necessary to block other growth factors in addition to VEGF to achieve complete inhibition of retinal NV. We recently demonstrated that a partially selective kinase inhibitor, PKC412, that blocks phosphorylation by VEGF and platelet-derived growth factor (PDGF) receptors and several isoforms of protein kinase C (PKC), completely inhibits retinal NV. In this study, we have used three additional selective kinase inhibitors with different selectivity profiles to explore the signaling pathways involved in retinal NV. PTK787, a drug that blocks phosphorylation by VEGF and PDGF receptors, but not PKC, completely inhibited retinal NV in murine oxygen-induced ischemic retinopathy and partially inhibited retinal vascularization during development. CGP 57148 and CGP 53716, two drugs that block phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on retinal NV. These data and our previously published study suggest that regardless of contributions by other growth factors, VEGF signaling plays a critical role in the pathogenesis of retinal NV. Inhibition of VEGF receptor kinase activity completely blocks retinal NV and is an excellent target for treatment of proliferative diabetic retinopathy and other ischemic retinopathies. 相似文献
33.
Precise control of cell proliferation and differentiation is critical for organogenesis. Geminin (Gem) has been proposed to link cell cycle exit and differentiation as a prodifferentiation factor and plays a role in neural cell fate acquisition. Here, we identified the SWI/SNF chromatin-remodeling protein Brg1 as an interacting partner of Gem. Brg1 has been implicated in cell cycle withdrawal and cellular differentiation. Surprisingly, we discovered that Gem antagonizes Brg1 activity during neurogenesis to maintain the undifferentiated cell state. Down-regulation of Gem expression normally precedes neuronal differentiation, and gain- and loss-of-function experiments in Xenopus embryos and mouse P19 cells demonstrated that Gem was essential to prevent premature neurogenesis. Misexpression of Gem also suppressed ectopic neurogenesis driven by Ngn and NeuroD. Gem's activity to block differentiation depended upon its ability to bind Brg1 and could be mediated by Gem's inhibition of proneural basic helix-loop-helix (bHLH)-Brg1 interactions required for bHLH target gene activation. Our data demonstrate a novel mechanism of Gem activity, through regulation of SWI/SNF chromatin-remodeling proteins, and indicate that Gem is an essential regulator of neurogenesis that can control the timing of neural progenitor differentiation and maintain the undifferentiated cell state. 相似文献
34.
Kim MS Seo KS Seong HS Cho SH Lee HB Hong KD Kim SK Khang G 《Bio-medical materials and engineering》2005,15(3):229-238
p-Carboxyphenoxy propane (CPP) prepolymer consisting of 4 units and sebacic acid (SA) prepolymer consisting of about 10 units were synthesized by reacting CPP and SA in the presence of excess acetic anhydride, respectively. Polyanhydride, poly(CPP-SA) copolymers were copolymerized by a melt polycondensation process with a mixture of CPP and SA prepolymer. Copolymers of average molecular weight up to 110,000 g/mol were achieved. The crystallinity of poly(CPP-SA) copolymers was decreased by the addition of the CPP homopolymer segment to SA homopolymer. Poly(CPP-SA) copolymers gradually degraded for period of 10 days. No large difference of weight loss observed according to molecular weight variation of poly(CPP-SA) copolymers. BCNU release from wafers fabricated by poly(CPP-SA) showed a sustained release pattern with no initial burst and delay of drug release. 相似文献
35.
The potent mutagen/carcinogen benzo[a]pyrene (B[a]P) is metabolically activated to (+)-anti-B[a]PDE, which induces a full spectrum of mutations primarily at the G:C base pairs (e.g. GC-->TA, GC-->AT, etc.). Each of these mutations can be induced by its major adduct [+ta]-B[a]P-N(2)-dG, where DNA sequence context appears to influence both the quantitative and qualitative pattern of mutagenesis. We noted previously that 5'-TG sequences tend to have a higher fraction of G-->T mutations for both [+ta]-B[a]P-N(2)-dG and (+)-anti-B[a]PDE in comparison with 5'-CG, 5'-GG or 5'-AG sequences. To investigate a possible structural element for this trend, the role (if any) of the methyl group on the 5'-T is considered. Using adduct site-specific means, the [G-->T/G-->A] mutational ratio for [+ta]-B[a]P-N(2)-dG is determined to be approximately 1.08 in a 5'-TGT sequence, and approximately 0.60 in a 5'-UGT sequence. (G-->C mutations are minor.) Although this modest approximately 1.8-fold decrease in [G-->T/G-->A] ratio is statistically significant (P = 0.03), it suggests that the methyl group on the 5'-T is not the main reason why a 5'-T tends to enhance G-->T mutations. This study was prompted by an adduct conformational hypothesis, which predicted that the removal of the methyl group in a 5'-TG sequence would lower the fraction of G-->T mutations; however, the approximately 1.8-fold decrease is too small to do additional experiments to assess whether this conformational hypothesis, or other hypotheses, are the true cause of the decrease, which is discussed in this paper. 相似文献
36.
Na Ri Kang Yo Han Ahn Eujin Park Keum Hwa Lee Hee Sun Baek Seong Heon Kim Heeyeon Cho Min Hyun Cho Jae Il Shin Joo Hoon Lee Hae Il Cheong Hee Gyung Kang Young Seo Park Il-Soo Ha Duk-Soo Moon Kyoung Hee Han 《Journal of Korean medical science》2021,36(20)
BackgroundChronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD.MethodsEighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years).ResultsThe mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs.ConclusionOn linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.Trial RegistrationClinicalTrials.gov Identifier: NCT02165878相似文献
37.
Park SH Park KS Park HG Lee HJ Seo JK Lee KH Kim DH Lee WH Lee CW Hong MK Park SW Park SJ 《Journal of Korean medical science》2003,18(4):585-588
This report describes an uncommon case of hypertrophic obstructive cardiomyopathy (HOCM) accompanying infundibular stenosis of the right ventricle treated by alcohol ablation therapy, in a 28-yr-old male patient presenting with dyspnea on exertion. HOCM with infundibular stenosis was detected by echocardiogram and cardiac catheterization and patient has dynamic obstructions of both ventricular outflow tracts. We performed alcohol ablation therapy to improve clinical symptoms and to relieve dynamic obstructions of both ventricular outflow tracts. This is the first case in which HOCM with infundibular stenosis of the right ventricle was treated by alcohol ablation therapy. 相似文献
38.
Acute effect of ethanol on firing patterns of Purkinje cells in the rat cerebellar slice preparation
This study examined the acute effects of ethanol (EtOH) on the firing patterns of Purkinje cells (PCs) using an intracellular recording in slice preparation of rat cerebellum. The experiments were performed in sagittal cerebellar slices (400 micrometer) of adult Sprague-Dawley rats (80-100g). Ethanol was applied by a bath superfusion with a known concentration expressed as the percentage of solution by volume (v/v) at 0.1, 0.5, 1, 2, and 4%. The result of the Chi-square test illustrated that the firing patterns were altered significantly after EtOH (p=0.007). However, the firing patterns that were altered by EtOH application were not affected by EtOH concentration (p= 0.1296). Among the 54 PCs tested, 30 PCs did not display any spontaneous firing activity and 24 PCs displayed spontaneous spike activity, either spiking in the simple manner (n=14) or cyclicly oscillating (n=10). In the presence of EtOH, 31 PCs were quiet, 22 PCs exhibited simple spiking activity and 1 PC continued to oscillate. Most PCs that displayed spontaneous activity before EtOH application progressively slowed their spike activity after EtOH superfusion. Especially, it was evident that 9 out of 10 oscillating PCs stopped their regular cyclic activity. In addition, 9 out of 14 PCs that displayed simple spike activity ceased to fire after EtOH application. Eleven out of 30 quiet PCs began to fire irregularly after EtOH application and this phenomenon usually occurred with membrane depolarization. EtOH induced spontaneous activity in 36.7% (11/30) of the quiescent PCs. In conclusion, there was differential EtOH sensitivity in the vitro slice preparation. EtOH depressed the endogenously generated spontaneous activity, especially the oscillatory firing activity. In contrast, the silent PCs were excited after EtOH application. Since this differential sensitivity persists in the presence of tetrodotoxin (TTX), it is suggested that this differential sensitivity is peculiar to the PCs. 相似文献
39.
Kim YS Cheon KA Kim BN Chang SA Yoo HJ Kim JW Cho SC Seo DH Bae MO So YK Noh JS Koh YJ McBurnett K Leventhal B 《Yonsei medical journal》2004,45(1):81-89
In order to develop a structured and objective diagnostic instrument, authors completed: (1) the translation and back translation of the Korean version of the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL) and (2) the examination of its validity and reliability of the K-SADS-PL-Korean version (K-SADS- PL) when used with Korean children. A total of 91 study subjects were recruited from child and adolescent psychiatry outpatient clinics. Clinical diagnoses were used as a gold standard for the examination of validity of K-SADS-PL-K. Consensual validity of threshold and sub-threshold diagnoses were good to excellent for attention-deficit/hyperactivity disorder (ADHD), fair for tic and oppositional defiant disorders, and poor to fair for anxiety and depressive disorders. Inter-rater and test-retest reliabilities were fair to excellent for ADHD and tic disorder. The significant correlations between the K-SADS-PL-K and Korean Child Behavior Checklist (K-CBCL) were found, which provided additional support for the concurrent validity of the K-SADS-PL-K. Sensitivities varied according to the diagnostic categories, but specificities remained high over all diagnoses, suggesting that the K-SADS-PL-K is a desirable confirmatory diagnostic tool. The results of this study suggest that the K-SADS-PL-K is an effective instrument for diagnosing major child psychiatric disorders, including ADHD, behavioral disorders and tic disorders in Korean children. Future studies will examine the validity and reliability of the K-SADS-PL-K in larger samples, including adolescents and community samples on a variety of child and adolescent psychiatric disorders. 相似文献
40.
Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon (PAH) and a potent mutagen/carcinogen found ubiquitously in the environment. B[a]P is primarily metabolized to diol epoxides, which react principally at N2-dG in DNA. B[a]P-N2-dG adducts have been shown to induce a variety of mutations, notably G-->T, G-->A, G-->C and -1 frameshifts. Four stereoisomers of B[a]P-N2-dG (designated: [+ta]-;, [+ca]-, [-ta] and [-ca]) were studied by NMR in duplex 11mers in a 5'-CGC sequence context, and each adopted a different adduct conformation (Geacintov, et al. (1997) Chem. Res. Toxicol., 10, 111). Herein these four identical B[a]P-containing 11mers are built into duplex plasmid genomes and mutagenesis studied in Escherichia coli following SOS-induction. In nucleotide excision repair (NER) proficient E.coli, no adduct-derived mutants are detected. In NER deficient E.coli, G-->T mutations dominate for all four stereoisomers [+ta]-, [+ca]-, [-ta] and [-ca]-B[a]P-N(2)-dG, and mutation frequency is similar. Thus, the mutagenic pattern for these four B[a]P-N2-dG stereoisomers is the same, in spite of the fact that they adopt dramatically different conformations in ds-oligonucleotides as determined by NMR. These findings suggest that adduct conformation must be fluid enough in the 5'-CGC sequence that the duplex DNA conformation can interconvert to mutagenic and non-mutagenic conformations during lesion-bypass. A comparison of all published studies with these four B[a]P-N2-dG stereoisomers in E.coli reveals that B[a]P-N2-dG adduct stereochemistry tends to have a lesser impact on mutagenic pattern (e.g. G-->T versus G-->A mutations) than does DNA sequence context, which is discussed. 相似文献