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Biomedical subjects

R Christian

Publications and source records attributed to R Christian.

At least 37 records · Page 2Linked to original sources
PubMed1993

EXP3174, a metabolite of losartan (MK 954, DuP 753) is more potent than losartan in blocking the angiotensin II-induced responses in vascular smooth muscle cells.

OBJECTIVE: EXP3174 is a metabolite of losartan (previous name DuP753), which is a non-peptide angiotensin II receptor antagonist. DESIGN: The inhibitory potency of these two antagonists on the angiotensin II-induced responses in vascular smooth muscle cells (VSMC) was investigated. METHODS: The effect of angiotensin II on cell growth was determined by [3H]-thymidine incorporation into cell DNA and by cellular protein measurements. Intracellular cytosolic Ca2+ concentration was measured by the fura-2 method. Inositolphosphates were determined by high-performance liquid chromatography after cell labelling with myo-[2-3H]-inositol. The early growth response gene-1 (Egr-1) messenger RNA (mRNA) expression was determined by the Northern blotting method. Binding and displacement studies of the antagonists were performed using [125I]-angiotensin II. RESULTS: An apparent dissociation constant (Kd) of 5.9 nmol/l for [125I]-angiotensin II (maximal binding coefficient 69 fmol/10(6) cells) was found. The specific binding of [125I]-angiotensin II to VSMC was inhibited by losartan, EXP3174 and saralasin with a half-maximal inhibitory concentration (IC50) of 1.0 X 10(-8), 1.1 X 10(-9) and 1.8 X 10(-9) mol/l, respectively. EXP3174 and losartan abolished the angiotensin II-induced formation of inositolphosphates in VSMC. EXP3174 and losartan inhibited the angiotensin II-induced elevation of intracellular cytosolic Ca2+ concentration with an IC50 of 5 X 10(-9) and 5 X 10(-8) mol/l, respectively. EXP3174 was more effective than losartan in blocking the angiotensin II-induced increase in Egr-1 mRNA. EXP3174 and losartan inhibited the angiotensin II-induced cell protein synthesis with an IC50 of 3 X 10(-9) and 4 X 10(-8) mol/l, respectively. CONCLUSIONS: These results indicate that EXP3174 is significantly more potent than losartan in blocking angiotensin II-induced cellular responses.

Angiotensin II↗
PubMed1993

Complete structure of the tyrosine-linked saccharide moiety from the surface layer glycoprotein of Clostridium thermohydrosulfuricum S102-70.

In this study, we have extended and completed a previous investigation (P. Messner, R. Christian, J. Kolbe, G. Schulz, and U. B. Sleytr, J. Bacteriol. 174:2236-2240, 1992) in which we demonstrated for the first time in prokaryotic organisms the presence of a novel O-glycosidic linkage via tyrosine. The surface layer glycoprotein of the eubacterium Clostridium thermohydrosulfuricum S102-70 is arranged in a hexagonal lattice, with center-to-center spacings of approximately 16.3 nm. Molecular weight determination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of both glycosylated and chemically deglycosylated surface layer glycoprotein showed values for the monomeric subunits of 94,000 and 87,500, respectively. Glycopeptide fractions obtained after exhaustive pronase digestion of purified, intact glycoprotein were isolated by reversed-phase liquid chromatography. One- and two-dimensional nuclear magnetic resonance studies, together with chemical analyses and plasma desorption time-of-flight mass spectrometry, were used to elucidate the structure of the hexasaccharide moiety linked by the novel O-glycosidic linkage to tyrosine. The combined evidence suggests the following structure: beta-D-Galf-(1-->3)-alpha-D-Galp- (1-->2)-alpha-L-Rhap-(1-->3)-alpha-D-Manp-(1--3)-alpha-L- Rhap-(1-->3)-beta- D-Glcp-(1-->4)-L-Tyr.

Bacterial Proteins↗
PubMed1992

A nuclear magnetic resonance spectroscopic investigation of Kdo-containing oligosaccharides related to the genus-specific epitope of Chlamydia lipopolysaccharides.

The 1H- and 13C-NMR parameters, chemical shifts and coupling constants, for the pentasaccharide of the genus-specific epitope of Chlamydia lipopolysaccharide and related di-, tri-, and tetra-saccharides have been measured and assigned completely using 1D and 2D techniques, and their structures have been confirmed. NOE experiments indicated the preferred conformation of the pentasaccharide and the component oligosaccharides. The 3JH,H demonstrate a change in conformation by rotation of the C-6-C-7 bond of the side chain of the (2----8)-linked Kdo (unit b) in alpha-Kdo-(2----8)-alpha-Kdo-(2----4)-alpha-Kdo-(2----6)-beta-GlcN-(1--- -6)- GlcNol, alpha-Kdo-(2----8)-alpha-Kdo-(2----4)-alpha-Kdo-(2----6)-beta-GlcNAc-(1- ---O)- allyl, and alpha-Kdo-(2----8)-alpha-Kdo-(2----4)-alpha-Kdo-(2----O)-allyl relative to that preferred in alpha-Kdo-(2----4)-alpha-Kdo-(2----6)-beta-GlcNAc-(1----O)-allyl, alpha-Kdo-(2----8)-alpha-Kdo-(2----O)-allyl, alpha-Kdo-(2----4)-alpha-Kdo-(2----O)-allyl, and alpha-Kdo-(2----6)-beta-GlcNAc-(1----O)-allyl, irrespective of the size of the aglycon, e.g., allyl or beta-D-GlcN residues. The conformational results have been substantiated by computer calculations using the HSEA approach.

Antigens, Bacterial↗
PubMed1992

Elucidation of the topological parameters of N-acetylneuraminic acid and some analogues involved in their interaction with the N-acetylneuraminate lyase from Clostridium perfringens.

A series of neuraminic acid derivatives modified in the side chain or at C-3, C-4 or C-5 were tested as substrates of inhibitors of N-acetylneuraminate lyase (EC 4.1.3.3) from Clostridium perfringens. The results, together with Km and Ki values reported previously, indicate that the region most important for the binding of sialic acids is an equatorial zone reaching from C-8 via the ring oxygen atom to C-4 of the sugar molecule, whereas the substituents at C-9 and C-5 may be varied to a higher extent without significantly disturbing enzyme action. It is shown that stereo-electronic factors are responsible for the immediate heterolytic fragmentation of the cyclic sialic acid into pyruvic acid and 2-acetamidomannose or a related C-6 sugar.

Clostridium perfringens↗
PubMed1992

Analysis of a novel linkage unit of O-linked carbohydrates from the crystalline surface layer glycoprotein of Clostridium thermohydrosulfuricum S102-70.

The surface layer glycoprotein of Clostridium thermohydrosulfuricum S102-70 was shown to contain a new type of glycan chain. Different from all known eubacterial glycoproteins, the saccharide moiety consists only of six sugar residues without any repeat sequences. Proteolytic digestion of purified S-layer glycoprotein resulted in isolation of several glycopeptide fractions. These are composed of the same hexasaccharide portion but are linked to oligopeptides of different length. One of them contains only a single amino acid. As concluded from chemical analyses and proton and carbon nuclear magnetic resonance spectroscopy of this preparation, the hexasaccharide moiety is linked via a novel O-glycosidic linkage. This is a beta-D-glucose residue linked to the phenolic hydroxyl group of tyrosine in intact S-layer glycoprotein.

Bacterial Outer Membrane Proteins↗
PubMed1990

Bacteriophage-associated glycan hydrolases specific for Escherichia coli capsular serotype K12.

Four bacteriophages were identified, which carry glycan hydrolases specific for the Escherichia coli K12 capsular polysaccharide. All these glycanases catalyze the hydrolysis of the alpha-L-rhamnosyl-1,5-beta-3-deoxy-D-manno-2-octulosonic acid linkage as demonstrated with a special thiobarbituric acid assay procedure, which discriminates between the C5 substituted and unsubstituted 3-deoxy-D-manno-2-octulosonic acid (dOclA). This assay, together with gel filtration, 1H-NMR and 13C-NMR spectroscopy showed that depolymerization led to the dimer of the K12 repeating unit, (,5-beta-dOcl1Ap-2,3-alpha-LRhap-1,2-alpha LRhap-1,)2, as the primary degradation product. The phages (phi 12-W, phi 12-S, phi 82-W1, phi 82-W2) were tested for their ability to infect Escherichia coli strains Su65-42 (O4:K12:H-) and CDC63-57 [O139:K82(12):H1]. phi 12-W and phi 12-S, respectively, infected strain Su65-42 only, phi 82-W2 CDC63-57 only, and phi 82-W1 both bacterial strains. These distinct host specificities cannot be explained by differences in the action of the glycanases, which depolymerize the capsules of both strains.

Coliphages↗
PubMed1990

Characterization of the surface layer glycoprotein of Clostridium symbiosum HB25.

The cell surface of Clostridium symbiosum HB25 is covered by a squarely arranged surface layer (S-layer) glycoprotein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the sodium dodecyl sulfate-soluble whole-cell extract showed the presence of several high-molecular-weight protein bands in a narrow range (approximate Mr, 140,000) which, upon periodic acid-Schiff staining, gave a positive reaction. After proteolytic degradation of the purified S-layer glycoprotein, a single glycopeptide fraction was obtained by gel permeation chromatography. Hydrolysis, treatment with aqueous hydrofluoric acid, and 1H and 13C nuclear magnetic resonance studies showed that the glycoprotein glycan is a high-molecular-weight polymer (approximate Mr, 15,000) of tetrasaccharide repeating units with the component sugars N-acetylgalactosamine (GalNAc), N-acetylmannosamine (ManNAc), and N-acetylbacillosamine (BacNAc; 2-N-acetyl-4-amino-2,4,6-trideoxy glucose) linked by monophosphate diesters. The following structure is proposed: [----6)-alpha-D-ManpNAc-(1----4)-beta-D-GalpNAc-(1----3)-alpha-D-+ ++BacpNAc- (1----4)-alpha-D-GalpNAc-(1----PO3)----]n. The nuclear magnetic resonance data provided evidence for a charge interaction between the free amino group of BacNAc and the phosphate group of adjacent glycan chains. Since polycationic ferritin did not label the cell surface of intact cells, an electrostatic interaction can also be expected in vivo, leading to a charge-neutral outer surface, which is characteristic of all other S layers from members of the family Bacillaceae studied so far.

Amino Acids↗
PubMed1989

The side-chain conformations of N-acetyl-7-,8-,9-deoxy-, and -4,7-dideoxy-neuraminic acid and their effect on the activation of CTP:N-acylneuraminic acid cytidylyltransferase.

The conformations of the deoxy side-chain analogs of N-acetylneuraminic acid and of N-acetyl-4-deoxyneuraminic acid have been studied by n.m.r. spectroscopy, which allowed us to distinguish between local minima conformations suggested by hard-sphere calculations. The conformations were correlated with the activity with CTP: N-acetylneuraminic acid cytidylyltransferase (CMPsialate synthase; EC 2.7.7.43).

Carbohydrate Conformation↗
PubMed1988

Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association.

One hundred thirty-eight patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally four times daily or tamoxifen 10 mg orally twice a day. Upon treatment failure patients were crossed over to the alternate treatment. Eligibility required that either the estrogen receptor (ER) or progesterone receptor (PR) be positive or that both values be unknown, and that the patients be at least 2 years post-spontaneous menopause or over 50 years of age. Pretreatment characteristics including performance status (PS), disease-free interval (DFI), receptor status, and prior treatment were similar for both groups. Only three patients had previous hormonal therapy while one third had prior chemotherapy. Objective response was determined using strict International Union Against Cancer (UICC) criteria. Seventeen of 61 patients achieved complete response (CR) or partial response (PR) on megestrol (28%) while 20 of 64 patients achieved CR or PR on tamoxifen (31%). Responses of skin and bone lesions were similar for both agents; however, more patients with visceral disease responded to tamoxifen. Response did not correlate with the level of ER or PR but was correlated with age. Both unadjusted and adjusted analysis of time to progression and adjusted analysis (for pretreatment variables) of survival showed significant differences favoring tamoxifen. Six of 44 patients (14%) crossed from megestrol to tamoxifen achieved CR or PR while only two of 38 patients (5%) crossed from tamoxifen to megestrol achieved response. Only one of the original patients randomized to megestrol remains on study, while 12 patients still remain on tamoxifen. These data indicate similar response rates for megestrol and tamoxifen; however, time to progression and overall survival significantly favor tamoxifen when used as first-line therapy in this trial.

Adult↗
PubMed1988

A comparison study of dynamic visual acuity between athletes and nonathletes.

A comparison study of dynamic visual acuity (DVA) was conducted using samples of nonathletic college students and college baseball players. The experimental population consisted of 17 male baseball players ranging in age from 19-24 years. The control population was made up of 25 male graduate students ranging in age from 23-29 years. Subjects reported the direction of a 20/25 "Landolt C" target exhibiting uniform angular motion produced by a projection system. Angular target velocities between 10 deg/sec and 110 deg/sec with an exposure time of 400 ms were used. The results showed a statistically significant difference between the two groups' DVA. The mean DVA for the baseball players was 82.35 deg/sec and 69.90 deg/sec for the control group.

Adult↗
PubMed1987

Isolation and structure determination of a diacetamidodideoxyuronic acid-containing glycan chain from the S-layer glycoprotein of Bacillus stearothermophilus NRS 2004/3a.

A glycan isolated from the surface-layer glycoprotein of Bacillus stearothermophilus strain NRS 2004/3a was shown by 1H- and 13C-n.m.r. spectroscopy to have the tetrasaccharide repeating-unit ----4)-beta-ManpA2,3(NAc)2-(1----3)-alpha-GlcpNAc-(1----4)-beta- ManpA2,3(NAc)-(1----6)-alpha-Glcp(1----.

Carbohydrate Conformation↗
PubMed1987

Artificial antigens. Synthesis of polyacrylamide copolymers containing 3-deoxy-D-manno-2-octulopyranosylonic acid (KDO) residues.

Starting from an anomeric mixture of methyl (allyl 4,5,7,8-tetra-O-acetyl-3-deoxy-alpha- and -beta-D-manno-2-octulopyranosid)onates, the glycosides sodium (allyl 3-deoxy-alpha- and -beta-D-manno-2-octulopyranosid)onate, sodium O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2----4)-[allyl 3-deoxy-alpha-D-manno-2-octulopyranosid]onate and sodium (allyl 3-deoxy-7-O-beta-D-ribofuranosyl-beta-D-manno-2-octulopyranosid)++ +onate were prepared in several steps. Radical copolymerization of the allyl glycosides with acrylamide afforded linear macromolecular antigens containing mono- and di-saccharide residues corresponding to the KDO-region of Salmonella minnesota rough-form lipopolysaccharide and to partial structures of the capsular polysaccharide from Escherichia coli K 23, respectively. The copolymers were substituted by KDO-residues in a ratio of 1:18 +/- 2 (based on acrylamide) and had molecular masses of 60-100 kdaltons.

Acrylic Resins↗
PubMed1987

On the side-chain conformation of N-acetylneuraminic acid and its epimers at C-7, C-8, and C-7,8.

The side-chain conformation of N-acetylneuraminic acid and analogs has been studied by n.m.r. spectroscopy. The results of the 1H-, 13C-n.m.r.-, and 1H-nuclear-Overhauser-enhancement measurements were used to distinguish between different local-minima conformations suggested by hard-sphere calculations. Attempts were made to correlate the major conformation determined for each compound with the behavior towards activation with N-acetylneuraminic acid-CMP-synthetase.

Carbohydrate Conformation↗