Effect of MDR1 haplotype on risk of Parkinson disease.

Background: MDR1, a multidrug transporter, encodes a P-glycoprotein that regulates the bioavailability of xenobiotics and is highly expressed at the blood-brain-barrier. Two single nucleotide polymorphisms (SNPs) (e21/2677[G/T/A] and e26/3435[C/T]) in the MDR1 gene can lead to differences in MDR1 expression and function. Specific MDR1 alleles of the 2 SNPs are positively selected among ethnic Chinese but not in the white population.

Surfactant effects upon dissolution patterns of carbamazepine immediate release tablet.

The objective of this study was to investigate the effects of sodium lauryl sulfate upon the saturation solubility of carbamazepine, its dissolution kinetics, and T50% defined as the time required for dissolving 50% of carbamazepine. Water, 0.1 N-HCl, and phosphate buffers at pH 4.

Norepinephrine transporter (NET) promoter and 5'-UTR polymorphisms: association analysis in panic disorder.

Several biochemical and pharmacological studies suggest that the catecholaminergic system involving the norepinephrine transporter (NET) is relevant for the pathogenesis of panic disorder. Three single nucleotide polymorphisms in the promoter or untranslated 5' region of the NET gene were investigated by means of RFLP analysis in a sample of 115 German patients with panic disorder and 115 matched controls. Statistical analysis failed to show association with the overall diagnosis of panic disorder.

Supercooling ability in two populations of the land snail Helix pomatia (Gastropoda: Helicidae) and ice-nucleating activity of gut bacteria.

The land snail Helix pomatia (Gastropoda: Helicidae) is widely distributed in Northern and Central Europe where it may experience subzero temperatures during winter months. Its supercooling ability was studied in two populations of H. pomatia.

Influence of endothelial nitric oxide synthase T-786C single nucleotide polymorphism on aneurysm size.

Object: Among patients with aneurysms, those with heterozygous (T/C) endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), a mutation reducing endothelial nitric oxide synthesis, are reported to have larger ruptured intracranial aneurysms (IAs) than those with homozygous (C/C or T/T) genotype. The authors tested patients harboring aneurysms for eNOS T-786C SNP in two populations--Japanese and Korean.

Methods: The eNOS T-786C SNP was genotyped through direct sequencing in genomic DNA obtained from 336 Japanese and 191 Korean patients with lAs and 214 Japanese and 191 Korean control volunteers.

Superconductivity in boron-doped diamond.

Superconductivity of boron-doped diamond, reported recently at T(c)=4 K, is investigated exploiting its electronic and vibrational analogies to MgB2. The deformation potential of the hole states arising from the C-C bond-stretch mode is 60% larger than the corresponding quantity in MgB2 that drives its high T(c), leading to very large electron-phonon matrix elements. The calculated coupling strength lambda approximately 0.

Analysis of MDR1 haplotypes in Parkinson's disease in a white population.

The MDR1 multidrug transporter is important in regulating environmental xenobiotics and hence may play a causative role in Parkinson's disease (PD). MDR1 haplotype comprising 2677 G > T/A and 3435 C > T may be protective against PD. Using a case control methodology, we investigated the association of MDR1 haplotypes (single nucleotide polymorphisms (SNPs) 2677 G > T/A and 3435 C > T) in a Polish PD population.

Effects of two P/S ratios with same peroxidizability index value and antioxidants supplementation on serum lipid concentration and hepatic enzyme activities of rats.

Background: High polyunsaturated/saturated fatty acid (P/S) ratio of diet decreases the risk of cardiovascular disease (CVD) with improvement of serum lipid profiles and inhibition of lipid peroxidation. This study was to investigate the effects of P/S ratio and antioxidants supplementation on lipid and peroxidation when dietary peroxidizability index (PI) value was the same.

Methods: Female Sprague-Dawley rats weighing 100-120 g were fed four different experimental diets for 4 weeks.

A novel class of achiral seco-analogs of CC-1065 and the duocarmycins: design, synthesis, DNA binding, and anticancer properties.

The synthesis, DNA binding properties, and in vitro and in vivo anticancer activity of fifteen achiral seco-cyclopropylindoline (or achiral seco-CI) analogs (5a-o) of CC-1065 and the duocarmycins are described. The achiral seco-CI analogs contain a 4-hydroxyphenethyl halide moiety that is attached to a wide range of indole, benzimidazole, pyrrole, and pyridyl-containing noncovalent binding components. The 4-hydroxyphenethyl halide moiety represents the simplest mimic of the seco-cyclopropylpyrroloindoline (seco-CPI) pharmacophore found in the natural products, and it lacks a chiral center.

Synthesis and evaluation of antitumor activity of 2- and 6-[(1,3-benzothiazol-2-yl)aminomethyl]-5,8-dimethoxy-1,4-naphthoquinone derivatives.

2- or 6-substituted BZT-N derivatives were synthesized, and their cytotoxic activity against cancer L1210 and SNU-1 cells was examined. The antitumor action was also assessed in mice bearing S-180 cells in peritoneal cavity. In a comparison, it was found that 6-substituted BZT-N derivatives exhibited higher potencies in both bioactivities than 2-substituted BZT-N derivatives against L1210 cells in in vitro and S-180 in vitro tests exception of compound 36.

Association of estrogen receptor 1 intron 1 C/T polymorphism in Korean vitiligo patients.

Background: Vitiligo is a common disease characterized by cutaneous white maculae due to loss of melanocytes. It is a polygenic disease, however, the exact pathogenesis of vitiligo is not yet known. The estrogen receptor (ESR) 1 gene was selected as a candidate gene because some researchers treated vitiligo successfully with the steroid-thyroid hormone mixture containing estrogen.

Estrogen receptor-alpha gene haplotype is associated with primary knee osteoarthritis in Korean population.

Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate ER-alpha gene polymorphisms for its associations with primary knee OA, we conducted a case-control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the ER-alpha gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA.

Cytokine gene polymorphisms in Taiwan.

Cytokine gene polymorphisms may affect their transcription, influence their level of production, and may be implicated in inducing susceptibility or resistance to diseases. Cytokine single-nucleotide polymorphisms (SNPs) were used to determine allelic and genotypic frequencies in the Minnan, the Hakka, and in four indigenous tribes: the Ami, the Tsou, the Atayal, and the Tao (or Yami). The following cytokine gene polymorphisms were analyzed: interleukin-1alpha (IL-1alpha) (T/C -889), IL-1beta (C/T -511, T/C +3962), IL-1R (C/T Pst-I 1970), IL-1Ralpha (T/C Mspa1-I 1100), IL-2 (T/G -330, G/T +166), IL-4 (T/G -1098, T/C -590, T/C -33), IL-4Ralpha (G/A +1902), IL-6 (G/C -174, G/A nt565), IL-10 (G/A -1082, C/T -819, C/A -592), IL-12 (C/A -1188), interferon-gamma (A/T UTR 5644), transforming growth factor-beta (C/T codon 10, G/C codon 25), and TNF-alpha (G/A -308, G/A -238).

Interfacial pinning in the superfluid 3He A-B transition in aerogel.

Continuous-wave NMR studies of 3He in the presence of 99.3% porosity silica aerogel at 34.0 bars and in a magnetic field of 28.

Folding of the Tetrahymena ribozyme by polyamines: importance of counterion valence and size.

Polyamines are abundant metabolites that directly influence gene expression. Although the role of polyamines in DNA condensation is well known, their role in RNA folding is less understood. Non-denaturing gel electrophoresis was used to monitor the equilibrium folding transitions of the Tetrahymena ribozyme in the presence of polyamines.

An unusual isotope effect in a high-transition-temperature superconductor.

In conventional superconductors, the electron pairing that allows superconductivity is caused by exchange of virtual phonons, which are quanta of lattice vibration. For high-transition-temperature (high-T(c)) superconductors, it is far from clear that phonons are involved in the pairing at all. For example, the negligible change in T(c) of optimally doped Bi2Sr2CaCu2O8+delta (Bi2212; ref.

ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics.

Background: A disintegrin and metalloprotease 33 (ADAM33) is expressed in the lung by fibroblasts and bronchial smooth muscle cells. Given its structure and cellular provenance, ADAM33 may be associated with airway remodelling and bronchial hyper-responsiveness. Single nucleotide polymorphisms (SNPs) and haplotypes of the ADAM33 gene have previously been associated with asthma susceptibility in the Caucasian population.

Kohn anomaly in MgB2 by inelastic X-ray scattering.

We study phonons in MgB2 using inelastic x-ray scattering (1.6 and 6 meV resolution). We clearly observe the softening and broadening of the crucial E(2g) mode through the Kohn anomaly along GammaM, in excellent agreement with ab initio calculations.

Staggered flux vortices and the superconducting transition in the layered cuprates.

We propose an effective model for the superconducting transition in the high-T(c) cuprates motivated by the SU(2) gauge theory approach. In addition to variations of the superconducting phase we allow for local admixture of staggered flux order. This leads to an unbinding transition of vortices with a staggered flux core that are energetically preferable to conventional vortices.

Synthesis and biological activity of novel platinum(II) complexes of glutamate tethered to hydrophilic hematoporphyrin derivatives.

A new series of hematoporphyrin-platinum(II) conjugates was prepared by platination of the glutamate ligand tethered to hydrophilic hematoporphyrin derivatives, in which different numbers of ethylene oxide unit were introduced to modulate the hydrophobic/hydrophilic balance of the conjugates. The antitumor activity of the hematoporphyrin-platinum(II) conjugates was assayed in vitro and in vivo against the leukemia L1210 cell line. Among the complexes, compound 11 exhibited not only higher in vivo activity (T/C% = 192) than cisplatin (T/C% = 184) and carboplatin (T/C% = 168), but also elevated tumor-localizing effect (tumor/muscle ratio > 3).

Molecular analysis of X-linked chronic granulomatous disease in five unrelated Korean patients.

Chronic granulomatous disease (CGD) is a fatal genetic disorder in which phagocytes fail to produce antimicrobial superoxide because of NADPH oxidase deficiency. Molecular defects in CYBB gene causing X-linked CGD are responsible for about 70% of all cases. This study was done to confirm genetic defects of CYBB gene in five Korean patients who were highly suggestive of having CGD by clinical history.

Telomerase and c-myc expression in hepatocellular carcinomas.

Background: Telomerase is activated in the majority of cancer tissues and immortalized cell lines. The hTERT (human telomerase reverse transcriptase-major component of telomerase) gene promoter has been cloned and contains many c-myc binding sites that mediate hTERT transcriptional activation. Thus far, the role of hTERT in tumorigenesis in hepatocellular carcinoma (HCC) has been little studied using RNA in situ hybridization.

Genetic polymorphisms in peroxisome proliferator-activated receptor delta associated with obesity.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. Three different PPARs, PPAR-alpha, -gamma, and -delta, have been characterized, and they are distinguished from each other by tissue distribution and cell activation. All PPARs are, to different extents, activated by fatty acids and derivatives.

Identification of variants in NFKBIA and association analysis with hepatocellular carcinoma risk among chronic HBV patients.

Human nuclear factor of kappa light chain gene enhancer in B cells inhibitor, alpha (NFKBIA) inhibits the action of NF-kappaB by forming a heterodimer with NF-kappaB, and preventing its translocation to the nucleus. We have sequenced a human NFKBIA full gene including -1000bp promoter region to identify its gene polymorphisms as a potential candidate gene for host genetic study of Hepatocellular Carcinoma (HCC). Nine novel single nucleotide polymorphisms (SNPs) and one GAA deletion were identified; two in promoter region (c.

Enhanced antitumor activity [correction for activitiy] of trans(+/-)-1,2-diaminocyclo- hexaneglutamatoplatinum(II) formulated with stealth liposome.

The antitumor platinum(II) compound, [Pt(dach)(Glu)] (dach=trans(+/-)-1,2-diaminocyclohexane, Glu=glutamate) was formulated with a stealth liposome to improve its biological activity. Liposomes were composed of PC/PEG2000-PE/CH (PC=1,2-diacyl-glycero-3-phosphocholine; PEG2000-PE=poly(ethylene glycol)2000-1,2-diacyl-glycero-3-phosphoethanolamine; CH=cholesterol) involving different acyl moieties of phospholipids such as DO (dioleoyl), DM (dimyristoyl) or DS (distearoyl) group. Among the different acyl groups in the stealth liposomes, the DM formulation was optimal for the preparation of the liposomal [Pt(dach)(Glu)] at the mole ratio of DMPC/PEG2000-DMPE/CH=50/5/45 and at the weight ratio of drug/lipid=1/20, which is represented as L-[Pt(dach)(Glu)].