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J An

Publications and source records attributed to J An.

At least 19 recordsLinked to original sources
PubMed2006

Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor.

Bcl-2 overexpression is an important mechanism underlying the aggressive behavior of prostate cancer cells and their resistance to radio- or chemotherapy. HA14-1, a recently discovered organic Bcl-2 inhibitor, potently induces apoptosis in various human cancer cells. Sequential exposure of radioresistant LNCaP (wild-type (wt) p53), LNCaP/Bcl-2 (wt p53) and PC3 (mutant p53) prostate cancer cells to a minimally cytotoxic concentration of 10 microM HA14-1 for 1 h followed by 1-6 Gy gamma radiation, resulted in a highly synergistic (combination index <1.0) induction of cell death as determined by an apoptosis assay at 72 h, and a clonogenicity assay at 12 days, after the initial treatment. The reverse treatment sequence did not cause a synergistic induction of cell death. When compared to individual treatments, cell death induced by the combined treatment was associated with dramatically increased reactive oxygen species (ROS) generation, c-Jun N-terminal kinase (JNK) activation, Bcl-2 phosphorylation, cytochrome c release, caspase-3 activation and DNA fragmentation. Exposure to either 200 microg/ml of the antioxidant alpha-tocopherol or 10 microM JNK inhibitor SP600125 before the combined treatment resulted in decreased activation of JNK and caspase-3 as well as decreased DNA fragmentation. However, treatment with the pancaspase inhibitor carbobenzoxyl-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone before the combined treatment inhibited apoptosis without affecting JNK activation, and this inhibitory effect was enhanced in the presence of alpha-tocopherol or SP600125. Taken together, our results indicate that HA14-1 potently sensitizes radioresistant LNCaP and PC3 cells to gamma radiation, regardless of the status of p53. ROS and JNK are important early signals that trigger both caspase-dependent and -independent cell death pathways and contribute to the apoptotic synergy induced by the combined treatments.

Apoptosis↗
PubMed2004

Spindle checkpoint and apoptotic response in alpha-particle transformed human bronchial epithelial cells.

The mitotic spindle checkpoint and apoptosis in response to nocodazole, a microtubule-disrupting agent, were investigated in the alpha-particle transformed human bronchial epithelial cell lines BERP35T1, BERP35T4 and the parental BEP2D cell line. When treated with 0.2 microg/ml of nocodazole, BEP2D and BERP35T1 cells were efficiently arrested in the mitotic phase, whilst BERP35T4, a transformed cell line showing chromosomal instability, failed to be arrested as evidenced by a low G2/M fraction. BERP35T4 cells also showed a higher proportion of aneuploids when treated with nocodazole or not. Thus, the BERP35T4 cell line has a defect in spindle checkpoint function. The extent of apoptosis induced by nocodazole (0.3 microg/ml) was significantly higher (2-fold to 2.5-fold) in BEP2D cells than in the two transformed cell lines. Furthermore, the induced apoptosis was found to occur predominantly before mitotic division in BEP2D cells. In BERP35T4 cells, however, 50% of induced apoptosis occurred before mitotic division and 50% occurred after division in binucleated cells when co-treated with cytochalasin B. The 5'-CpG island of the Chfr gene, a mitotic checkpoint gene that functions in entry into metaphase, was found to be methylated in BERP35T4 cells but not in BEP2D cells. Consistent with methylation, the expression of the Chfr gene was markedly suppressed in BERP35T4 cells. Our results suggest that the impaired spindle checkpoint and abnormal apoptotic response may be related to the oncogenic progression of human bronchial epithelial cells initiated by exposure to alpha-particles.

Alpha Particles↗
PubMed2004

Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas.

Primary effusion lymphomas (PELs) are a rare type of non-Hodgkin's lymphoma that are resistant to cytotoxic chemotherapy. PELs manifest constitutive activation of nuclear factor kappa B (NF-kappaB), and inhibition of NF-kappaB induces apoptosis of PELs and sensitizes to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced death. Bortezomib (PS-341), a peptidyl boronic acid inhibitor of the proteasome, is a potent agent against a wide range of hematologic malignancies and has been shown to inhibit NF-kappaB. Thus, we examined the cytotoxic effects of bortezomib alone and in combination with various drugs. Bortezomib potently inhibited NF-kappaB in PEL cells in a dose-dependent manner. In addition, bortezomib inhibited growth and induced apoptosis of PEL cell lines (IC(50) values of 3.4-5.0 nM). Results of drug interactions between bortezomib and chemotherapy (doxorubicin and Taxol) were schedule-dependent: synergistic interactions were generally observed when PEL cells were pretreated with bortezomib prior to chemotherapy, whereas additive or even antagonistic interactions occurred with chemotherapy pretreatment or simultaneous treatment with bortezomib and chemotherapy. Most schedules of bortezomib and dexamethasone were synergistic, although pretreatment with dexamethasone resulted in additive interactions. Effects of combinations of bortezomib and TRAIL were generally additive. Thus, bortezomib represents a promising potential therapy for the treatment of PEL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Comparison of hyperkalemic cardioplegia with altered [CaCl2] and [MgCl2] on [Ca2+]i transients and function after warm global ischemia in isolated hearts.

AIM: [MgCl(2)] and [CaCl(2)] may modify the cardioprotective effects of hyperkalemic cardioplegia (CP). We changed [MgCl(2)] and [CaCl(2)] in a CP solution to examine their effects on [Ca(2+)]i transients and cardiac function before and after global normothermic ischemia. METHODS: After stabilization and loading of indo 1-AM in Kreb's solution (KR), each heart was perfused with either KR or 1 of 4 CP solutions before 37 degrees C, 30 min ischemia followed by reperfusion with KR. The KR solution contained, in mM, 4.5 KCl, 2.4 MgCl(2) and 2.5 CaCl(2); the CP solutions had in addition to 18 KCl: CP 1 (control CP): 2.4 MgCl(2), 2.5 CaCl(2); CP 2: 7.2 MgCl(2), 2.5 CaCl(2); CP 3, 7.2 MgCl(2), 1.25 CaCl(2); CP 4: 2.4 MgCl(2), 1.25 CaCl(2). RESULTS: In the KR group [Ca(2+)]i markedly increased on early reperfusion while functional return (LVP, dLVP/dt((max and min))) was much reduced; each CP group led to reduced [Ca(2+)]i loading and improved function. The rates of cytosolic Ca(2+) fluxes (d[Ca(2+)]/dt(max) and d[Ca(2+)]/dt(min)) increased significantly compared to baseline in the KR group, but were mostly suppressed in the CP groups, and d[Ca(2+)]/dt(min) was lower after CP 4 compared to CP 1 on reperfusion. At 60 min reperfusion, LVP area to [Ca(2+)] area and cardiac efficiency to phasic [Ca(2+)] relationships were shifted after KR, but not after CP 1-4. With similar functional recovery, [Ca(2+)] transient and [Ca(2+)] area were significantly lower after CP 4 than after CP 1. CONCLUSION: Increasing [MgCl(2)] (CP 2 and 3) did not improve cardiac function or reduce Ca(2+) transients on reperfusion better than the other CP groups, but reducing [CaCl(2)] (CP 3 and 4) was more effective in reducing [Ca(2+)] transients on reperfusion after global ischemia.

Animals↗
PubMed2002

Variable-temperature scanning tunneling microscopy and scanning tunneling spectroscopy study on copper phthalocyanine ultrathin films on a Au(111) surface.

Variable-temperature high-resolution scanning tunneling microscopy (STM) images reveal that well-ordered copper phthalocyanine (CuPc) strips can be self-assembled by depositing CuPc molecules on a Au(111) surface. The self-assembled strips are supposed to result from the balance of the intermolecular interaction and the interaction between the molecules and substrate during annealing. The energy band (approximately 1.9-2.1 eV) of CuPc, measured by scanning tunneling spectroscopy (STS), is comparable to the optical band gap (approximately 1.7 eV). Spectroscopic measurements confirm that a dipole layer and/or an effect of image force exist at the CuPc/Au(111) interface.

Crystallization↗
PubMed2001

Estrogen receptor beta-selective transcriptional activity and recruitment of coregulators by phytoestrogens.

Estrogens used in hormone replacement therapy regimens may increase the risk of developing breast cancer. Paradoxically, high consumption of plant-derived phytoestrogens, particularly soybean isoflavones, is associated with a low incidence of breast cancer. To explore the molecular basis for these potential different clinical outcomes, we investigated whether soybean isoflavones elicit distinct transcriptional actions from estrogens. Our results demonstrate that the estrogen 17beta-estradiol effectively triggers the transcriptional activation and repression pathways with both estrogen receptors (ERs) ERalpha and ERbeta. In contrast, soybean isoflavones (genistein, daidzein, and biochanin A) are ERbeta-selective agonists of transcriptional repression and activation at physiological levels. The molecular mechanism for ERbeta selectivity by isoflavones involves their capacity to create an activation function-2 surface of ERbeta that has a greater affinity for coregulators than ERalpha. Phytoestrogens may act as natural selective estrogen receptor modulators that elicit distinct clinical effects from estrogens used for hormone replacement by selectively recruiting coregulatory proteins to ERbeta that trigger transcriptional pathways.

Animals↗
PubMed2001

Overexpression of the P46 (T1) translocase component of the glucose-6-phosphatase complex in hepatocytes impairs glycogen accumulation via hydrolysis of glucose 1-phosphate.

The final step of gluconeogenesis and glycogenolysis is catalyzed by the glucose-6-phosphatase (Glc-6-Pase) enzyme complex, located in the endoplasmic reticulum. The complex consists of a 36-kDa catalytic subunit (P36), a 46-kDa glucose 6-phosphate translocase (P46), and putative glucose and inorganic phosphate transporters. Mutations in the genes encoding P36 or P46 have been linked to glycogen storage diseases type Ia and type Ib, respectively. However, the relative roles of these two proteins in control of the rate of glucose 6-phosphate hydrolysis have not been defined. To gain insight into this area, we have constructed a recombinant adenovirus containing the cDNA encoding human P46 (AdCMV-P46) and treated rat hepatocytes with this virus, or a virus encoding P36 (AdCMV-P36), or the combination of both viruses, resulting in large and equivalent increases in expression of the transgenes within 8-24 h of viral treatment. The overexpressed P46 protein was appropriately targeted to hepatocyte microsomes and caused a 58% increase in glucose 6-phosphate hydrolysis in nondetergent-treated (intact) microsomal preparations relative to controls, whereas overexpression of P36 caused a 3.6-fold increase. Overexpression of P46 caused a 50% inhibition of glycogen accumulation in hepatocytes from fasted rats incubated at 25 mm glucose relative to cells treated with a control virus (AdCMV-betaGAL). Furthermore, in hepatocytes from fed rats cultured at 25 mm glucose and then exposed to 15 mm glucose, AdCMV-P46 treatment activated glycogenolysis, as indicated by a 50% reduction in glycogen content relative to AdCMV-betaGAL-treated controls. In contrast, overexpression of P46 had only small effects on glycolysis, whereas overexpression of P36 had large effects on both glycogen metabolism and glycolysis, even in the presence of co-overexpressed glucokinase. Finally, P46 overexpression enhanced glucose 1-phosphate but not fructose 6-phosphate hydrolysis in intact microsomes, providing a mechanism by which P46 overexpression may exert its preferential effects on glycogen metabolism.

Animals↗
PubMed2001

Thermodynamic database for protein-nucleic acid interactions (ProNIT).

MOTIVATION: Protein-nucleic acid interactions are fundamental to the regulation of gene expression. In order to elucidate the molecular mechanism of protein-nucleic acid recognition and analyze the gene regulation network, not only structural data but also quantitative binding data are necessary. Although there are structural databases for proteins and nucleic acids, there exists no database for their experimental binding data. Thus, we have developed a Thermodynamic Database for Protein-Nucleic Acid Interactions (ProNIT). RESULTS: We have collected experimentally observed binding data from the literature. ProNIT contains several important thermodynamic data for protein-nucleic acid binding, such as dissociation constant (K(d)), association constant (K(a)), Gibbs free energy change (DeltaG), enthalpy change (DeltaH), heat capacity change (DeltaC(p)), experimental conditions, structural information of proteins, nucleic acids and the complex, and literature information. These data are integrated into a relational database system together with structural and functional information to provide flexible searching facilities by using combinations of various terms and parameters. A www interface allows users to search for data based on various conditions, with different display and sorting options, and to visualize molecular structures and their interactions. AVAILABILITY: ProNIT is freely accessible at the URL http://www.rtc.riken.go.jp/jouhou/pronit/pronit.html.

Amino Acid Sequence↗
PubMed2001

Changes in [Na(+)](i), compartmental [Ca(2+)], and NADH with dysfunction after global ischemia in intact hearts.

We measured the effects of global ischemia and reperfusion on intracellular Na(+), NADH, cytosolic and mitochondrial (subscript mito) Ca(2+), relaxation, metabolism, contractility, and Ca(2+) sensitivity in the intact heart. Langendorff-prepared guinea pig hearts were crystalloid perfused, and the left ventricular (LV) pressure (LVP), first derivative of LVP (LV dP/dt), coronary flow, and O(2) extraction and consumption were measured before, during, and after 30-min global ischemia and 60-min reperfusion. Ca(2+), Na(+), and NADH were measured by luminescence spectrophotometry at the LV free wall using indo 1 and sodium benzofuran isophthalate, respectively, after subtracting changes in tissue autofluorescence (NADH). Mitochondrial Ca(2+) was assessed by quenching cytosolic indo 1 with MnCl(2). Mechanical responses to changes in cytosolic-systolic (subscript sys), diastolic (subscript dia), and mitochondrial Ca(2+) were tested over a range of extracellular [Ca(2+)] before and after ischemia-reperfusion. Both [Ca(2+)](sys) and [Ca(2+)](dia) doubled at 1-min reperfusion but returned to preischemia values within 10 min, whereas [Ca(2+)](mito) was elevated over 60-min reperfusion. Reperfusion dissociated [Ca(2+)](dia) and [Ca(2+)](sys) from contractile function as LVP(sys-dia) and the rise in LV dP/dt (LV dP/dt(max)) were depressed by one-third and the fall in LV dP/dt (LV dP/dt(min)) was depressed by one-half at 30-min reperfusion, whereas LVP(dia) remained markedly elevated. [Ca(2+)](sys-dia) sensitivity at 100% LV dP/dt(max) was not altered after reperfusion, but [Ca(2+)](dia) at 100% LV dP/dt(min) and [Ca(2+)](mito) at 100% LV dP/dt(max) were markedly shifted right on reperfusion (ED(50) +36 and +125 nM [Ca(2+)], respectively) with no change in slope. NADH doubled during ischemia but returned to normal on initial reperfusion. The intracellular [Na(+)] ([Na(+)](i)) increased minimally during ischemia but doubled on reperfusion and remained elevated at 60-min reperfusion. Thus Na(+) and Ca(2+) temporally accumulate during initial reperfusion, and cytosolic Ca(2+) returns toward normal, whereas [Na(+)](i) and [Ca(2+)](mito) remain elevated on later reperfusion. Na(+) loading likely contributes to Ca(2+) overload and contractile dysfunction during reperfusion.

Animals↗
PubMed2001

Ischemic and anesthetic preconditioning reduces cytosolic [Ca2+] and improves Ca(2+) responses in intact hearts.

Ca(+) loading during reperfusion after myocardial ischemia is linked to reduced cardiac function. Like ischemic preconditioning (IPC), a volatile anesthetic given briefly before ischemia can reduce reperfusion injury. We determined whether IPC and sevoflurane preconditioning (SPC) before ischemia equivalently improve mechanical and metabolic function, reduce cytosolic Ca(2+) loading, and improve myocardial Ca(2+) responsiveness. Four groups of guinea pig isolated hearts were perfused: no ischemia, no treatment before 30-min global ischemia and 60-min reperfusion (control), IPC (two 2-min occlusions) before ischemia, and SPC (3.5 vol%, two 2-min exposures) before ischemia. Intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured at the left ventricular (LV) free wall with the fluorescent probe indo 1. Ca(2+) responsiveness was assessed by changing extracellular [Ca(2+)]. In control hearts, initial reperfusion increased diastolic [Ca(2+)] and diastolic LV pressure (LVP), and the maximal and minimal derivatives of LVP (dLVP/dt(max) and dLVP/dt(min), respectively), O(2) consumption, and cardiac efficiency (CE). Throughout reperfusion, IPC and SPC similarly reduced ischemic contracture, ventricular fibrillation, and enzyme release, attenuated rises in systolic and diastolic [Ca(2+)], improved contractile and relaxation indexes, O(2) consumption, and CE, and reduced infarct size. Diastolic [Ca(2+)] at 50% dLVP/dt(min) was right shifted by 32-53 +/- 8 nM after 30-min reperfusion for all groups. Phasic [Ca(2+)] at 50% dLVP/dt(max) was not altered in control but was left shifted by -235 +/- 40 nM [Ca(2+)] after IPC and by -135 +/- 20 nM [Ca(2+)] after SPC. Both SPC and IPC similarly reduce Ca(2+) loading, while augmenting contractile responsiveness to Ca(2+), improving postischemia cardiac function and attenuating permanent damage.

Anesthetics, Inhalation↗
PubMed2001

Blocking Na(+)/H(+) exchange reduces [Na(+)](i) and [Ca(2+)](i) load after ischemia and improves function in intact hearts.

We determined in intact hearts whether inhibition of Na(+)/H(+) exchange (NHE) decreases intracellular Na(+) and Ca(2+) during ischemia and reperfusion, improves function during reperfusion, and reduces infarct size. Guinea pig isolated hearts were perfused with Krebs-Ringer solution at 37 degrees C. Left ventricular (LV) free wall intracellular Na(+) concentration ([Na(+)](i)) and intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured using fluorescence dyes. Hearts were exposed to 30 min of ischemia with or without 10 microM of benzamide (BIIB-513), a selective NHE-1 inhibitor, infused for 10 min just before ischemia or for 10 min immediately on reperfusion. At 2 min of reperfusion, BIIB-513 given before ischemia decreased peak increases in [Na(+)](i) and [Ca(2+)](i), respectively, from 2.5 and 2.3 times (controls) to 1.6 and 1.3 times pre-ischemia values. At 30 min of reperfusion, BIIB-513 increased systolic-diastolic LV pressure (LVP) from 49 +/- 2% (controls) to 80 +/- 2% of pre-ischemia values. BIIB-513 reduced ventricular fibrillation by 54% and reduced infarct size from 64 +/- 1% to 20 +/- 3%. First derivative of the LVP, O(2) consumption, and cardiac efficiency were also improved by BIIB-513. Similar results were obtained with BIIB-513 given on reperfusion. These data show that Na(+) loading is a marker of reperfusion injury in intact hearts in that inhibiting NHE reduces Na(+) and Ca(2+) loading during reperfusion while improving function. These results clearly implicate the ionic basis by which inhibiting NHE protects the guinea pig intact heart from ischemia-reperfusion injury.

Animals↗
PubMed2000

Overexpression of a modified human malonyl-CoA decarboxylase blocks the glucose-induced increase in malonyl-CoA level but has no impact on insulin secretion in INS-1-derived (832/13) beta-cells.

The long-chain acyl-CoA (LC-CoA) model of glucose-stimulated insulin secretion (GSIS) holds that secretion is linked to a glucose-induced increase in malonyl-CoA level and accumulation of LC-CoA in the cytosol. We have previously tested the validity of this proposal by overexpressing goose malonyl-CoA decarboxylase (MCD) in INS-1 cells, but these studies have been criticized due to: 1) the small insulin secretion response (2-4-fold) of the INS-1 cells used; 2) unknown contribution of the ATP-sensitive K(+) (K(ATP)) channel-independent pathway of GSIS in INS-1 cells, which has been implicated as the site at which lipids regulate insulin granule exocytosis; and 3) deletion of the N-terminal mitochondrial targeting sequence, but not the C-terminal peroxisomal targeting sequence in the goose MCD construct, raising the possibility that a significant fraction of the overexpressed enzyme was localized to peroxisomes. To address these outstanding concerns, INS-1-derived 832/13 cells, which exhibit robust K(ATP) channel-dependent and -independent pathways of GSIS, were treated with a new adenovirus encoding human MCD lacking both its mitochondrial and peroxisomal targeting sequences (AdCMV-MCD Delta 5), resulting in large increases in cytosolic MCD activity. Treatment of 832/13 cells with AdCMV-MCD Delta 5 completely blocked the glucose-induced rise in malonyl-CoA and attenuated the inhibitory effect of glucose on fatty acid oxidation. However, MCD overexpression had no effect on K(ATP) channel-dependent or -independent GSIS in 832/13 cells. Furthermore, combined treatment of 832/13 cells with AdCMV-MCD Delta 5 and triacsin C, an inhibitor of long chain acyl-CoA synthetase that reduces LC-CoA levels, did not impair GSIS. These findings extend our previous observations and are not consistent with the LC-CoA hypothesis as originally set forth.

Adenoviridae↗
PubMed2000

Reduced cytosolic Ca(2+) loading and improved cardiac function after cardioplegic cold storage of guinea pig isolated hearts.

BACKGROUND: Hypothermia is cardioprotective, but it causes Ca(2+) loading and reduced function on rewarming. The aim was to associate changes in cytosolic Ca(2+) with function in intact hearts before, during, and after cold storage with or without cardioplegia (CP). METHODS AND RESULTS: Guinea pig hearts were initially perfused at 37 degrees C with Krebs-Ringer's (KR) solution (in mmol/L: Ca(2+) 2.5, K(+) 5, Mg(2+) 2.4). One group was perfused with CP solution (Ca(2+) 2.5, K(+) 18, Mg(2+) 7.2) during cooling and storage at 3 degrees C for 4 hours; another was perfused with KR. LV pressure (LVP), dP/dt, O(2) consumption, and cardiac efficiency were monitored. Cytosolic phasic [Ca(2+)] was calculated from indo 1 fluorescence signals obtained at the LV free wall. Cooling with KR increased diastolic and phasic [Ca(2+)], whereas cooling with CP suppressed phasic [Ca(2+)] and reduced the rise in diastolic [Ca(2+)]. Reperfusion with warm KR increased phasic [Ca(2+)] 86% more after CP at 20 minutes and did not increase diastolic [Ca(2+)] at 60 minutes, compared with a 20% increase in phasic [Ca(2+)] after KR. During early and later reperfusion after CP, there was a 126% and 50% better return of LVP than after KR; during later reperfusion, O(2) consumption was 23% higher and cardiac efficiency was 38% higher after CP than after KR. CONCLUSIONS: CP decreases the rise in cardiac diastolic [Ca(2+)] observed during cold storage in KR. Decreased diastolic [Ca(2+)] and increased systolic [Ca(2+)] after CP improves function on reperfusion because of reduced Ca(2+) loading during and immediately after cold CP storage.

Animals↗
PubMed2000

ProTherm, version 2.0: thermodynamic database for proteins and mutants.

ProTherm 2.0 is the second release of the Thermo-dynamic Database for Proteins and Mutants that includes numerical data for several thermodynamic parameters, structural information, experimental methods and conditions, functional and literature information. The present release contains >5500 entries, an approximately 67% increase over the previous version. In addition, we have included information about reversibility of data, details about buffer and ion concentrations and the surrounding residues in space for all mutants. A WWW interface enables users to search data based on various conditions with different sorting options for outputs. Further, ProTherm has links with other structural and literature databases, and the mutation sites and surrounding residues are automatically mapped on the structures and can be directly viewed through 3DinSight developed in our laboratory. The ProTherm database is freely available through the WWW at http://www.rtc.riken.go.jp/protherm.html

Databases, Factual↗
PubMed2000

Effect of Ar ion irradiation on electrochemical behaviors of zircaloy-4

In order to investigate the effect of the damage on the electrochemical behavior, zircaloy-4 specimens were irradiated by Ar ions using an accelerator at an energy of 50 keV, with doses from 3 x 10(14) to 3 x 10(16) ions/cm2 at liquid nitrogen temperature. Potentiodynamic polarization measurements were employed to evaluate the corrosion resistance of zircaloy-4 in a 0.5 M H2SO4 water solution at room temperature. A damage efficiency function on the passive current density of the polarization curve was defined and deduced theoretically.

Journal Article↗
PubMed2000

Linkage of the genes controlling natural killer cell activity to HLA-B.

OBJECTIVE: To study whether there is a relationship between HLA-B alleles and low natural killer(NK) cell activity in Chinese. METHODS: The subjects were 34 unrelated healthy individuals (10 males and 24 females), aged 25-60 years, and 31 individuals (17 males and 14 females) from 11 families, aged 22-70 years, previously genotyped for HLA class I, II, complotypes and haplotypes that were assigned based on family studies. The unrelated individuals were typed for HLA-A, -B antigen by a microcytotoxicity assay and all the subjects were tested for NK cell activity by lactate dehydrogenase (LDH) enzyme-release assay. RESULTS: Statistical analysis showed that 30 lysis unit(LU) was the cutoff value of low and high NK reactors. The frequency of low reactor individuals homozygous for HLA-B was significantly higher than that for those for HLA-DR(P< 0. 05). The associated genes included HLA-B13, B40, B46, B7, B57, defined as NKB1 genes, and HLA-B44 as NKB2 gene. Family studies provide further evidence that the genes controlling low NK cell activity were located in the MHC region and it was a recessive trait. CONCLUSION: There were recessive genes associated with HLA-B controlling low NK cell activity in Chinese. The NKB alleles were partly different from those found in Caucasian.

Adult↗
PubMed2000

Utility of the Arabidopsis FAE1 and yeast SLC1-1 genes for improvements in erucic acid and oil content in rapeseed.

High-erucic acid (HEA) Brassica napus cultivars are regaining interest in industrial contexts. Erucic acid and its derivatives are important renewable raw materials utilized in the manufacture of plastic films, in the synthesis of Nylon 13,13, and in the lubricant and emollient industries. Theoretically, the highest level of erucic acid that can be achieved by means of classical breeding is 66 mol%; however, using new approaches on the basis of genetic engineering, it might be possible to develop a B. napus cultivar containing levels of erucic acid significantly above 66 mol% (>80 mol%). In an attempt to increase the amounts of very-long-chain fatty acids (VLCFAs), and erucic acid in particular, in Canadian HEA B. napus cultivars, we have focused on two targets using a transgenic approach. We examined both the role/function of the Arabidopsis thaliana FAE1 (fatty acid elongase) gene by expressing it under the control of the seed-specific napin promoter in B. napus germplasm with analysis of the changes in VLCFA content in the seed oil of transgenic lines, and the performance of the yeast SLC1-1 (sphingolipid compensation mutant) in B. napus cv. Hero transgenic progeny in the field. Here, we report analyses of the contents of 22:1, total VLCFAand oil in the seed oil, as well as seed yield of the field-grown FAE1 and SLC1-1 B. napus cv. Hero progeny.

Acetyltransferases↗