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PubMed1980

Blood groups and types, hemoglobin variants, and G-6-PD deficiency among Abu Dhabians in the United Arab Emirates.

Some erythrocyte genetic factors were studied in the indigenous population of Abu Dhabi, the capital of the United Arab Emirates, on the southeastern coast of the Arabian peninsula. Determinations carried out included blood groups and types ABO, MNS, Rh0, KkJsa, FyaFyb, P1, Lea, Vela, hemoglobin variants, and screening for G-6-PD deficiency. Prevalence of most blood groups and types harmonized with that among neighboring Arabs and some Arabs elsewhere. The MS and NS gene complexes were noticeably high. African admixture was expressed by the presence of Jsa and HbS and large numbers of Fy. G-6-PD deficiency was rather high.

Blood Group Antigens↗
PubMed2004

New types of soluble polymer-supported bisphosphine ligands with a cyclobutane backbone for Pd-catalyzed enantioselective allylic substitution reactions.

A highly efficient and practical optical resolution of anti head-to-head racemic coumarin dimer 7 has been achieved by molecular complexation with TADDOL, (-)-8, through a hydrogen bonding interaction to afford the corresponding two enantiomers, (-)- and (+)-7, in 70 and 75 % yields, respectively, with >99 % ee. Starting from enantiopure (-)-7, a new type of C2-symmetric bisphosphine ligand (S,S,S,S)-3 with a cyclobutane backbone has been synthesized in good yield by facile transformations. The asymmetric induction efficiency of these chiral bisphosphine ligands in Pd-catalyzed asymmetric allylic substitution reactions was evaluated. Under the experimental conditions, the allylic substitution products could be obtained in excellent yields (up to 99 %) and enantioselectivities (up to 98.9 % ee). By taking advantage of the high enantioselectivity of this catalytic reaction and the easily derivable carboxylate groups on the cyclobutane backbone of ligand (S,S,S,S)-3, a new type of analogous ligand (S,S,S,S)-4 as well as the MeO-PEG-supported soluble ligand (S,S,S,S)-5 (PEG=polyethylene glycol) have also been synthesized and utilized in asymmetric allylic substitution reactions. In particular, the MeO-PEG supported (S,S,S,S)-5 b had a synergistic effect on the enantioselectivity of the reaction compared with its nonsupported precursor (S,S,S,S)-4 c, affording the corresponding allylation products 14 a and 14 b with excellent enantioselectivities (94.6 and 97.2 % ee, respectively). Moreover, the Pd complex of (S,S,S,S)-5 b could easily be recovered and recycled several times without significant loss of enantioselectivity and activity in the allylic substitution reactions.

Allyl Compounds↗
PubMed2005

Cyclic enolates of Ni and Pd: equilibrium between C- and O-bound tautomers and reactivity studies.

2-acylaryl complexes of Ni and Pd containing chelating diphosphines react with KtBuO to give metallacyclic enolate complexes. While coordination through the carbon atom is preferred in the case of Pd, the nickel O-enolate compounds are formed as the corresponding O-tautomers. Slow equilibration between O- and C-enolate tautomers is observed for the nickel complex with an unsubstituted enolate function (M-O-C=CH(2)). Theoretical DFT calculations suggest that the barrier for the tautomer exchange has its origin in the rigidity of the metallacycle. Whilst the C-enolate tautomer is unreactive towards aldehydes, the corresponding O-enolate adds to MeCHO and PhCHO, giving rise to products that retain the enolate functionality. The carbonylation of these products cleanly leads to the formation of enol lactones in a highly selective manner.

Journal Article↗
PubMed2006

Deconvoluting the memory effect in Pd-catalyzed allylic alkylation: Effect of leaving group and added chloride.

An analysis of product distributions in the Tsuji-Trost reaction indicates that several instances of reported "memory effects" can be attributed to slow interconversion of the initially formed syn- and anti-[Pd(eta3-allyl)] complexes. Addition of chloride triggers a true memory effect, in which the allylic terminus originally bearing the leaving group has a higher reactivity. The latter effect, termed regioretention, can be rationalized by ionization from a palladium complex bearing a chloride ion, forming an unsymmetrically substituted [Pd(eta3-allyl)] complex. DFT calculations verify that the position trans to the phosphine ligand is more reactive both in the initial ionization and in the subsequent nucleophilic attack.

Journal Article↗
PubMedDate not supplied

The biocompatibility of a dental Ag-Pd-Cu-Au-based casting alloy and its structural components.

The biocompatibility of type III casting gold alloy, an Ag-Pd-Cu-Au-based dental casting alloy and its two main structural components, a CuPd-rich and an Ag-rich phase, was studied after subcutaneous implantation for 7 weeks in 20 guinea pigs. The Ag-Pd-Cu-Au alloy was surrounded by a capsule of immature collagen with fibroblasts and an increased vascular supply. The CuPd-rich component induced and maintained an acute inflammation with highly vascularized granulation tissue. The tissue reaction to the Ag-rich component and the Au-based alloy was slight. Ten of the guinea pigs were sensitized to PdCl2 prior to the implantation period, but this caused no enhanced tissue reaction, except for an increase in the number of mast cells around three of the alloys.

Animals↗
PubMedDate not supplied

In vitro cytotoxicity of Ag-Pd-Cu-based casting alloys.

The cytotoxicity and its correlation to alloy composition, structure, corrosion, as well as galvanic coupling was studied with 12 Ag-Pd-Cu-type alloys, one conventional type III gold alloy and pure Ag, Cu, and Pd. The agar overlay cell culture technique was used. Single phase binary CuPd alloys were only slightly cytotoxic below a Cu content of 30 wt%. The tested multiphase alloys were all toxic, but no correlation between toxicity and Cu content could be observed. Solid solution annealing increased the cytotoxicity of a multiphase alloy. Exposure of a single phase alloy to an artificial saliva for 1 week prior to the test decreased its cytotoxicity significantly. Galvanic coupling of the alloys through an outer copper wire decreased their cytotoxicity.

Biocompatible Materials↗
PubMed2004

Overexpression of regucalcin suppresses cell death and apoptosis in cloned rat hepatoma H4-II-E cells induced by lipopolysaccharide, PD 98059, dibucaine, or Bay K 8644.

The effect of regucalcin, a regulatory protein in intracellular signaling pathway, on cell death was investigated by using the cloned rat hepatoma H4-II-E cells overexpressing regucalcin. The hepatoma cells (wild-type) and stable regucalcin (RC)/pCXN2 transfectants were cultured for 72 h in medium containing 10% fetal bovine serum (FBS) to obtain subconfluent monolayers. After culture for 72 h, cells were further cultured for 12-72 h in medium without FBS containing either vehicle or lipopolysaccharide (LPS; 0.1 or 1.0 microg/ml). The number of wild-type cells was significantly decreased by culture for 24 or 48 h in the presence of LPS (0.1 or 1.0 microg/ml). The effect of LPS (0.1 or 1.0 microg/ml) in decreasing the number of hepatoma cells was significantly prevented in transfectants overexpressing regucalcin. However, the culture with LPS (0.1 or 1.0 microg/ml) for 72 h caused a significant decrease in cell number of transfectants. Ca(2+)/calmodulin-dependent nitric oxide (NO) synthase activity was significantly decreased by culture with LPS (1.0 microg/ml) for 24-72 h of wild-type cells. This decrease was significantly prevented in transfectants. LPS (0.1 or 1.0 microg/ml)-induced decrease in the number of wild-type cells was significantly prevented by culture with caspase-3 inhibitor (10(-8) M). Moreover, the number of wild-type cells was significantly decreased by culture with PD 98059 (10(-6) M), dibucaine (10(-6) M), or staurosporine (10(-6) M), which is an inhibitor of various protein kinases. The effect of PD 98059 or dibucaine on the number of wild-type cells was not observed in transfectants, although the effect of staurosporine was seen in transfectants. Culture with Bay K 8644 (2.5 x 10(-6) M), an agonist of Ca(2+) entry in cells, caused a significant decrease in the number of wild-type cells. Such an effect was not seen in transfectants. The presence of LPS did not significantly decrease the number of wild-type cells in the presence of Bay K 8644. Agarose gel electrophoresis showed the presence of low-molecular-weight deoxyribonucleic acid (DNA) fragments of adherent wild-type cells cultured with Bay K 8644, and this DNA fragmentation was significantly prevented in transfectants. This study demonstrates that overexpression of regucalcin has a suppressive effect on cell death induced by LPS or various intracellular signaling-related factors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

PD 90780, a non peptide inhibitor of nerve growth factor's binding to the P75 NGF receptor.

Nerve growth factor is a peptide that supports the survival and differentiation of discrete neuronal populations in the peripheral and central nervous systems. NGF binds to both trkA, a tyrosine kinase receptor, and to the p75 nerve growth factor receptor, a protein lacking a consensus signalling sequence. We have identified a substituted pyrazoloquinazolinone, PD 90780, which inhibits binding of nerve growth factor to the p75 receptor. This inhibition of binding occurs due to PD 90780 binding to nerve growth factor, not to the p75 receptor. This compound may be useful in identifying the region(s) of nerve growth factor involved in binding to the p75 receptor and in clarifying the role of p75 receptor in the actions of the neurotrophins.

Animals↗
PubMed1998

Discovery and development of an endothelin A receptor-selective antagonist PD 156707.

PD 156707 is a highly potent, selective antagonist of the ETA receptor that has demonstrated efficacy in a number of different disease models. The next few years will be exciting in the field of ET research as several compounds progress through clinical development. It is our hope that the efficacy that data demonstrated to date with PD 156707 will some day be translated into real hope for the patients who are waiting beyond the confines of our research laboratories.

Animals↗
PubMed2003

Neural stem/progenitor cells survive and differentiate better in PD rats than in normal rats.

To investigate the effects of grafted neural stem/mesencephalic progenitor cells (NSCs/MP) on rotational behavior of Parkinson's disease (PD) rats and the influence of intracerebral environment on NSCs/MP, we observed the survival and differentiation of NSCs/MP transplanted into 6-hydroxydopamine (6-OHDA)-lesioned and intact striatums. NSCs/MP were prepared from E(11-15) rats and proliferated in serum-free medium with bFGF for several weeks. One day after being primed with serum/dbcAMP to differentiate, cell suspensions were grafted into 6-OHDA-lesioned and intact striatums respectively. It had been found that NSCs/MP were able to survive better and differentiate into more tyrosine hydroxylase (TH)-positive neurons in 6-OHDA-lesioned striatums than in intact ones, and apomorphine-induced rotations were obviously attenuated in MP graft models. The data suggested that NSCs/MP tend to survive and differentiate into TH-positive neurons in 6-OHDA-lesioned striatums. The data demonstrated that striatums in which DAergic terminals are destroyed by 6-OHDA undergo some changes and thus provide more appropriate conditions for NSCs/MP to differentiate into mature DAergic neurons. Furthermore, the finding that MP had greater relieving effects on rotational behavior than NSCs suggests that NSCs could not be used in clinical therapy of PD unless being induced into MP in vitro before transplantation.

Animals↗
PubMed2003

Mesencephalic progenitors can improve rotational behavior and reconstruct nigrostriatal pathway in PD rats.

The aim of this study was to investigate the possibility of mesencephalic progenitors (MP) in treating Parkinson's disease (PD). MP were prepared from E(11-13) rats and proliferated in serum-free medium with basic fibroblast growth factor (bFGF) for 10 days. Cells were then collected and implanted into the striatum only--single grafts or simultaneously into the substantia nigra (SN) and the striatum--double grafts. Twelve weeks after transplantation, DiI, a fluorescent dye, was microinjected into the ipsilateral striatum. Using this strategy, it was found that MP of double grafts had more potent effects on rotational behavior than that of single grafts. Injection of the retrograde tracer DiI into the striatum resulted in fluorescent-labeled cells within the intranigral grafts in double grafts. These data greatly support that MP transplants could not only improve rotational behavior, but does help to re-establish nigrostriatal connections so that it may become one efficient way in treating PD.

Animals↗
PubMed1982

G-6-PD Guadalajara. A new mutant associated with chronic nonspherocytic hemolytic anemia.

This paper describes a new G-6-PD variant designated Guadalajara, which was found in a Mexican boy suffering from chronic hemolytic anemia. The red cell enzyme activity of the subject is about 14%. The mutant enzyme showed rapid electrophoretic mobility, slightly increased affinity for glucose-6-phosphate, slightly decreased affinity for NADP+, moderately elevated utilization of substrate analogues, and normal heat stability, pH curve, and inhibition by NADPH. G-6-PD Guadalajara differs from all previously reported variants and is the first variant associated with chronic hemolysis found in Mexico.

Anemia, Hemolytic, Congenital↗
PubMed1987

Electrical PD, short-circuit current and fluxes of Na and Cl across avian intestine.

In vitro measurements were made of transmural potential difference (PD), short-circuit current (Isc), resistance and unidirectional fluxes of 22Na and 36Cl across the duodenum, jejunum, ileum and colon of normal sodium-replete domestic fowl (Gallus domesticus). The PD ranged from about 1 mV across the duodenum to 8 mV across the colon while the Isc was, respectively, 2.8 and 64 microA X cm-2. The jejunum and ileum exhibited values between these extremes. Unidirectional fluxes (under short-circuit conditions) of Na and Cl were lowest across the duodenum where there was no evidence of active transport of these ions. Unidirectional fluxes of Na and Cl were less across the jejunum than across the ileum or colon. A net active transport of Na (but not Cl) was observed in the ileum (= 106% of the Isc) and colon (= 50% of Isc). The possible physiological significance of these observations in the domestic fowl are discussed and are compared to that of a mammal, the rabbit.

Animals↗
PubMed1975

G-6-PD Poznań, variant with severe enzyme deficiency.

A new variant of G-6-PD with severe enzyme dificiency without chronic hemolysis is characterized. The biochemical properties of the variant closely resemble those of the G-6-PD Ramat-Gan described in a case of chronic non-spherocytic hemolytic anemia. As the family data on linking of chronic hemolysis with Ramat-Gan variant are lacking, the differentiation of the variants on the basis of clinical manifestations is not well-founded.

Child, Preschool↗
PubMed1992

Susceptibility of anaerobic bacteria to PD 131628.

The in vitro activity of PD 131628 against anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, Bacteroides spp. and fusobacteria was determined by the agar dilution method. This activity was compared with that of ciprofloxacin, piperacillin, cefoxitin, imipenem, clindamycin, metronidazole and chloramphenicol. PD 131628, imipenem, clindamycin, metronidazole and chloramphenicol were the most active agents tested.

Anti-Infective Agents↗
PubMed2006

Pharmacokinetic-pharmacodynamic (PK-PD) modeling of cardiovascular effects of metoprolol in spontaneously hypertensive rats: a microdialysis study.

The present work addressed possible alterations in the pharmacokinetics and the in vivo pharmacodynamic of metoprolol (MET) in spontaneously hypertensive (SH) rats and Wistar Kyoto (WKY) animals by means of the microdialysis technique. The correlation between MET unbound plasma concentrations and its pharmacological effects, such as heart rate and blood pressure change, was also examined in SH and WKY rats by the application of a PK-PD model. MET dialysate concentrations and its chronotropic and blood pressure effect were determined during 3 h after the administration of 3 and 10 mg.kg(-1) of the drug. A PK-PD model with a separate effect compartment was used to analyse the data. A good correlation between plasma MET concentrations and its hypotensive and chronotropic effect was found in all experimental groups. Although a greater maximal effect (E(max)) for the antihypertensive effect of MET was observed in SH rats (WKY: E(max): -17+/-1 mmHg; SH: E(max): -28+/-4 mmHg; P<0.05 versus WKY rats), no differences were found in the concentration yielding half-maximal response (IC(50)) comparing SH (IC(50): 583+/-146 ng x ml(-1)) and WKY animals (IC(50): 639+/-187 ng x ml(-1)). The bradycardic effect of MET was greater in SH rats (E(max): -29+/-1%, P<0.05 versus WKY rats) than in WK animals (E(max): -22+/-2%), but no differences were observed in the IC(50) comparing both experimental groups (WKY: IC(50): 187+/-53 ng x ml(-1); SH: IC(50): 216+/-62 ng x ml(-1)). Pharmacokinetic analysis shows that the volume of distribution of MET was greater in SH rats (Vd: 3.4+/-0.5 l, P<0.05 versus WKY rats) with regard to Wistar Kyoto (WKY) animals (Vd: 1.9+/-0.2 l). The results suggest that the pharmacokinetic behaviour of metoprolol are modified in SH rats, resulting in an increased volume of distribution. A greater maximal efficacy to the hypotensive effect of metoprolol was observed in SH rats, suggesting participation of beta-adrenoceptors in the maintenance of the hypertension. Also, a greater chronotropic response to metoprolol was found in the hypertensive group compared with WKY animals, suggesting that, at least in part, the greater cardiac effect of metoprolol explained the enhanced hypotensive response of the beta blocker in the SH animals.

Adrenergic beta-Antagonists↗
PubMed2000

Isotope dilution inductively coupled plasma quadrupole mass spectrometry in connection with a chromatographic separation for ultra trace determinations of platinum group elements (Pt, Pd, Ru, Ir) in environmental samples.

An isotope dilution inductively coupled plasma quadrupole mass spectrometric (ID-ICP-QMS) method was developed for the simultaneous determination of the platinum group elements Pt, Pd, Ru, and Ir in environmental samples. Spike solutions, enriched with the isotopes 194Pt, 108Pd, 99Ru, and 191Ir, were used for the isotope dilution step. Interfering elements were eliminated by chromatographic separation using an anion-exchange resin. Samples were dissolved with aqua regia in a high pressure asher. Additional dissolution of possible silicate portions by hydrofluoric acid was usually not necessary. Detection limits of 0.15 ng x g(-1), 0.075 ng x g(-1), and 0.015 ng x g(-1) were achieved for Pt, Pd, Ru, and Ir, respectively, using sample weights of only 0.2 g. The reliability of the ID-ICP-QMS method was demonstrated by analyzing a Canadian geological reference material and by participating in an interlaboratory study for the determination of platinum and palladium in a homogenized road dust sample. Surface soil, sampled at different distances from a highway, showed concentrations in the range of 0.1-87 ng x g(-1). An exponential decrease of the platinum and palladium concentration with increasing distance and a small anthropogenic contribution to the natural background concentration of ruthenium and iridium was found in these samples.

Chromatography, Ion Exchange↗
PubMed2006

Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers.

PURPOSE: The programmed death-1 (PD-1)/B7-H1 (also called PD-L1) pathway negatively regulates T cell activation and has been suggested to play an important role in regulating antitumor host immunity. To investigate the clinical significance of B7-H1 expression to the tumor grade and postoperative prognosis of patients with urothelial cancer, we analyzed the relationship between B7-H1 expression and various clinicopathological features and postoperative prognosis. EXPERIMENTAL DESIGN: Sixty-five urothelial cancer cases were examined. B7-H1 expression in tumors and the numbers and phenotypes of tumor-infiltrating lymphocytes were evaluated by immunohistochemistry and flow cytometry. RESULTS: A substantial expression of B7-H1 was observed in all urothelial cancers investigated. Tumor specimens from patients with higher WHO grade or primary tumor classifications showed significantly higher percentages of tumor-associated B7-H1. Tumor-associated B7-H1 expression was significantly associated with a high frequency of postoperative recurrence and poor survival rate. Furthermore, multivariate analysis indicated that tumor-associated B7-H1 was more significant prognostic factor than WHO grade. CONCLUSIONS: Our results demonstrate that the aberrant expression of B7-H1 in urothelial cancer is associated with aggressive tumors, suggesting a regulatory role of tumor-associated B7-H1 in antitumor immunity. Therefore, the manipulation of tumor-associated B7-H1 may become a beneficial target for immunotherapy in human urothelial cancer.

Antigens, CD↗