Search PubMed⌕ Search

Biomedical subjects

M Santer

Publications and source records attributed to M Santer.

At least 19 recordsLinked to original sources
PubMed2002

Optical response of two-dimensional electron fluids beyond the kohn regime: strong nonparabolic confinement and intense laser light.

We investigate the linear and nonlinear optical response of two-dimensional interacting electron fluids confined by a strong nonparabolic potential. We show that such fluids may exhibit higher-harmonic spectra under realistic experimental conditions. Higher harmonics arise as the electrons explore anharmonicities of the confinement potential (electron-electron interactions reduce this nonlinear effect). This opens the possibility of controlling the optical functionality by engineering the confinement potential. Our results were obtained within time-dependent density-functional theory. A classical hydrodynamical model is in good agreement with the quantum-mechanical results.

Journal Article↗
PubMed2001

Platelet glycoprotein V binds to collagen and participates in platelet adhesion and aggregation.

Glycoprotein V (GPV) is a subunit of the platelet GPIb-V-IX receptor for von Willebrand factor and thrombin. GPV is cleaved from the platelet surface during activation by thrombin, but its role in hemostasis is still unknown. It is reported that GPV knockout mice had a decreased tendency to form arterial occluding thrombi in an intravital thrombosis model and abnormal platelet interaction with the subendothelium. In vitro, GPV-deficient platelets exhibited defective adhesion to a collagen type I-coated surface under flow or static conditions. Aggregation studies demonstrated a decreased response of the GPV-deficient platelets to collagen, reflected by an increased lag phase and reduced amplitude of aggregation. Responses to adenosine diphosphate, arachidonic acid, and the thromboxane analog U46619 were normal but were enhanced to low thrombin concentrations. The defect of GPV null platelets made them more sensitive to inhibition by the anti-GPVI monoclonal antibody (mAb) JAQ1, and this was also the case in aspirin- or apyrase-treated platelets. Moreover, an mAb (V.3) against the extracellular domain of human GPV selectively inhibited collagen-induced aggregation in human or rat platelets. V.3 injected in rats as a bolus decreased the ex vivo collagen aggregation response without affecting the platelet count. Finally, surface plasmon resonance studies demonstrated binding of recombinant soluble GPV on a collagen-coupled matrix. In conclusion, GPV binds to collagen and appears to be required for normal platelet responses to this agonist. (Blood. 2001;98:1038-1046)

Animals↗
PubMed2001

Universal eigenvector statistics in a quantum scattering ensemble.

We calculate eigenvector statistics in an ensemble of non-Hermitian matrices describing open quantum systems [F. Haake et al., Z. Phys. B 88, 359 (1992)] in the limit of large matrix size. We show that ensemble-averaged eigenvector correlations corresponding to eigenvalues in the center of the support of the density of states in the complex plane are described by an expression recently derived for Ginibre's ensemble of random non-Hermitian matrices.

Journal Article↗
PubMed2001

A novel monoclonal antibody against the extracellular domain of GPIbbeta modulates vWF mediated platelet adhesion.

GPIbbeta is disulfide-linked to GPIbalpha to form GPIb, a platelet receptor for von Willebrand factor (vWF). GPIb is in turn non covalently linked to GPIX and GPV to form the GPIb/V/IX complex. Apart from its contribution to controlling surface expression of the complex, the exact function of GPIbbeta is not well established due to a lack of suitable ligands or antibodies. The present report describes a monoclonal antibody (RAM.1) that labeled the 26 kDa GPIbbeta subunit on western blots and coprecipitated the three subunits of the GPIb/IX complex from lysates of platelets and transfected CHO and K562 cells. RAM.1 bound to GPIbbeta deleted of its intracellular domain whereas Gi27, directed against intracellular GPIbbeta, did not. Using synthetic peptides, the RAM.1 epitope was mapped to a putative cysteine loop within the COOH-terminal leucine-rich flanking region. In functional assays, RAM.1 had no effect on platelet aggregation induced by ADP, collagen or thrombin, but inhibited ristocetin induced platelet agglutination and botrocetin induced vWF binding. RAM.1 inhibited adhesion of GPIb/V/IX transfected K562 cells to a vWF matrix under flow, increased their rolling velocity and decreased the resistance of cells to detachment at high shear. This study suggests a role of GPIbbeta in modulating the adhesive properties of GPIb/V/IX and describes a useful tool to analyze the exact functions of GPIbbeta.

Animals↗
PubMed2000

Opportunistic screening for chlamydia infection in general practice: can we reach young women?

OBJECTIVE: To study opportunistic screening in primary care, in such a way that would include teenage women. Setting-Screening for chlamydia infection was offered opportunistically in eight general practices in Edinburgh to women aged < or = 35 years attending for cervical smear, and women aged < or = 20 years attending for contraception. The numbers of women eligible to be offered screening were 901 in the cervical smear group, and 595 in the contraception group. RESULTS: Effective screening rate (offered test, consented, and urine sample returned) was 30% for the cervical smear group compared with 23% for the contraception group. Among those tested, chlamydia prevalence was strongly associated with young age, ranging from 11.8% in those <18 years, to 0% in those >25 years. Number of sexual partners in past year did not improve prediction of infection. CONCLUSION: These findings raise concerns regarding the feasibility of opportunistic screening in general practice, particularly for those with highest prevalence of chlamydia--teenage women.

Adolescent↗
PubMed1995

A mutation at the universally conserved position 529 in Escherichia coli 16S rRNA creates a functional but highly error prone ribosome.

A base substitution of G to U was constructed at position 529 in Escherichia coli 16S rRNA. The U529 mutant ribosomes were functional and present on polysomes but were highly error prone and caused a progressive loss of cell viability. They displayed elevated levels of readthrough of stop codons and frameshifting, and an increase in thermal sensitivity of beta-galactosidase, suggestive of missense errors. These results demonstrate that the university conserved G529 is involved in tRNA selection at the A site during protein synthesis.

Base Sequence↗
PubMed1993

Functional effects of a G to U base change at position 530 in a highly conserved loop of Escherichia coli 16S RNA.

Any base change at position 530 introduced into Escherichia coli on a multicopy plasmid leads to cell death [Powers & Noller (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 1042-1046]. It was suggested that these mutants cannot carry out chain elongation. To define more precisely the function of base 530, we have studied ribosomes in which G530 was mutated to U530. In vivo, U530 16S rRNA was incorporated into 30S subunits and could combine with 50S to make 70S ribosomes. 16S rRNA in vitro transcripts containing U530 were assembled into 30S ribosomes, and their activity was tested in defined steps of protein synthesis. Mutant 30S ribosomes were as active as wild-type in poly(U)-dependent poly(Phe) synthesis, P- and A-site tRNA binding, and 30S initiation complex formation. 30S initiation complexes, in the presence of 50S, could react with puromycin like the wild-type. The rate, extent, and position of cross-linking of AcVal-tRNA in the P site to 16S RNA were identical in mutant and wild-type ribosomes. Although there appeared to be no defect in 70S initiation complex formation or in direct A-site binding of Phe-tRNA dependent on poly(U), U530 30S ribosomes were nevertheless defective in carrying out synthesis of fMet-Val dipeptide using natural mRNA. Mutant 30S ribosomes were also refractory to streptomycin-induced misreading although no misreading was observed in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1990

Base changes at position 792 of Escherichia coli 16S rRNA affect assembly of 70S ribosomes.

To investigate the function of base 792 of 16S rRNA in 30S ribosomes of Escherichia coli, the wild-type (adenine) residue was changed to guanine, cytosine, or uracil by oligonucleotide-directed mutagenesis. Each base change conferred a unique phenotype on the cells. Cells containing plasmid pKK3535 with G792 or T792 showed no difference in generation time in LB broth containing ampicillin, whereas cells with C792 exhibited a 20% increase in generation time in this medium. To study the effect on cell growth of a homogeneous population of mutant ribosomes, the mutations were cloned into the 16S rRNA gene on pKK3535 carrying a spectinomycin-resistance marker (thymine at position 1192), and the cells were grown with spectinomycin. Cells containing G792 or C792 showed 16% and 56% increases in generation time, respectively, and a concomitant decrease in 35S assimilation into proteins. Cells with T792 did not grow in spectinomycin-containing medium. Maxicell analyses indicated decreasing ability to form 70S ribosomes from 30S subunits containing guanine, cytosine, or uracil at position 792 in 16S rRNA. It appeared that C792-containing 30S ribosomes had lost the ability to bind initiation factor 3.

Base Sequence↗
PubMed1987

A single base change in the Shine-Dalgarno region of 16S rRNA of Escherichia coli affects translation of many proteins.

A single base mutation was constructed at position 1538 of Escherichia coli 16S rRNA, changing a cytidine to a uridine. This position is in the Shine-Dalgarno region, thought to be involved in base-pairing to mRNA during initiation of protein synthesis. The mutation was constructed by using a synthetic oligodeoxynucleotide that differs in sequence by one base from the wild-type sequence of 16S rRNA. This oligonucleotide was used as a primer on single-stranded DNA of phage M13, into which was cloned a specific region of DNA encoding 16S rRNA. The mutation is lethal when expressed from the normal promoters of rRNA operons, P1 and P2, in a high-copy-number plasmid. Expression can be repressed by a temperature-sensitive repressor, cI857, in combination with the bacteriophage lambda PL promoter. Induction of transcription by temperature shift yields mutant 16S rRNA that is processed and assembled into functional ribosomal subunits. The presence of mutant ribosomes retards cell growth and dramatically alters incorporation of [35S]methionine into a large proportion of the cellular proteins. The change in level of synthesis of individual proteins correlates with the change in base-pairing between mutant rRNA and the Shine-Dalgarno region of the mRNA.

Bacterial Proteins↗
PubMed1986

Effect of various treatments of gamma-globulin (IgG) for achieving intravenous tolerance on the capacity to interact with human monocyte Fc receptors. A comparative study.

Gamma-globulins for intravenous application (IgG-IV), processed by various methods, were tested for their ability to interact with human monocyte Fc receptors by determining the dose required to inhibit monocyte Fc receptor-mediated rosette formation and phagocytosis by half (ID50). Since dimeric and oligomeric IgG were found to be 2-3 times and 5-15 times more potent, respectively, than monomeric IgG, the varying proportions of polymeric IgG in intact IgG-IV were corrected for by calculation. The results of the rosette formation and phagocytosis tests were closely correlated, and insignificant differences between preparations processed by the same procedure were noted, while considerable differences were found between different procedures. The decreasing order of inhibitory activity was DEAE-Sephadex-treated IgG, acid-treated IgG, plasmin-digested IgG, polyethylene glycol(PEG)-precipitated IgG, IgG subjected to reduction/alkylation, IgG that underwent sulfitolysis, IgG treated with beta-propiolactone, and finally pepsin-treated IgG. Thus, while mild procedures preserve the capacity of IgG to interact with monocyte Fc receptors, chemical modification severely interferes with this important effector function.

Humans↗
PubMed1979

Comparative surfact structure of 16S ribosomal ribonucleic acid of 30S ribosomes of procaryotic cells.

Ribonuclease T(1) treatment of 30S ribosomes of Escherichia coli converts a large region at the 3' OH end of 16S ribosomal ribonucleic acid (rRNA) to low-molecular-weight RNA. The final 25 nucleotides at the 3' terminus of the molecule emerge relatively intact, whereas most of the region "upstream," for about 150 nucleotides, is converted to oligonucleotides. Identical enzyme treatment generates a fragment of about 60 nucleotides from the middle of 16S rRNA (section D'). To determine whether there are similar sequences in other bacteria, which occupy similar accessible surface locations, we treated 30S ribosomes from Azotobacter vinelandii and Bacillus stearothermophilus with RNase T(1). In each case, a fragment of RNA about 25 nucleotides in length containing the 3' OH end of 16S rRNA and a fragment of about 60 nucleotides in length similar, but not identical, in oligonucleotide composition to section D' of E. coli 16S rRNA were obtained from nuclease-treated 30S ribosomes. These data indicate that, although the primary structure at the 3' end and the middle (section D') of the various 16S rRNA's is not completely conserved, their respective conformations are conserved. A number of identical oligonucleotides were found in the low-molecular-weight fraction obtained from RNase T(1)-treated E. coli, A. vinelandii, and B. stearothermophilus 30S ribosomes. These results show that identical RNase T(1)-sensitive sequences are present in all three bacteria. Hydrolysis of these regions leads to the production of the fragments 25 and 60 nucleotides in length.

Azotobacter↗
PubMed1978

Conservation of the primary structure at the 3' end of 18S rRNA from eucaryotic cells.

DNA sequencing methods have been used to determine a sequence of about 20 nucleotides at the 3' termini of various 18S (small ribosomal subunit) RNA molecules. Polyadenylated rRNA was first synthesized using the enzyme ATP:polynucleotidyl transferase from mainze. Then in the presence of an oligonucleotide primer uniquely complementary to the end of each adenylated rRNA, a cDNA copy was produced using AMV reverse transcriptase. In every case, the cDNA transcript was of finite size, which we ascribe to the appearance of an oligonucleotide containing m62A near the 3' end of the 18S rRNAs. Sequences at the 3' termini of 18S rRNA molecules from the four eucaryotic species examined here (mouse, silk worm, wheat embryo and slime mold) are highly conserved. They also exhibit strong homology to the 3' end of E. coli 16S rRNA. Two important differences, however, are apparent. First, the 16S sequence CCUCC, implicated in mRNA binding by E. coli ribosomes, is absent from each eucaryotic rRNA sequence. Second, a purine-rich region which exhibits extensive complementarity to the 5' noncoding regions of many eucaryotic mRNAs appears consistently.

Animals↗
PubMed1977

Area of 16S ribonucleic acid at or near the interface between 30S and 50S ribosomes of Escherichia coli.

To determine the region of 16S ribonucleic acid (RNA) at the interface between 30 and 50S ribosomes of Escherichia coli, 30 and 70S ribosomes were treated with T1 ribonuclease (RNase). The accessibility of 16S RNA in the 5' half of the molecule is the same in 30 and 70S ribosomes. The interaction with 50S ribosomes decreases the sensitivity to T1 RNase of an area in the middle of 16S RNA. A large area near the 3' end of 16S RNA is completely protected in 70S ribosomes. The RNA near the 3' end of the molecule and an area of RNA in the middle of the molecule appear to be at the interface between 30 and 50S ribosomes. One site in 16S RNA, 13 to 15 nucleotides from the 3' end, normally inaccessible to T1 RNase in 30S ribosomes, becomes accessible to T1 RNase in 70S ribosomes. This indicates a conformational change at the 3' end of 16S RNA when 30S ribosomes are associated with 50S ribosomes.

Ammonium Chloride↗
PubMed1973

Action of ribonuclease T1 on 30S ribosomes of Escherichia coli and its role in sequence studies on 16S ribonucleic acid.

Two large ribonucleic acid (RNA) fragments have been obtained from T1-RNase-treated 30S ribosomes of Escherichia coli. One fragment, about 475 nucleotides long, contains all the unique oligonucleotides found by Fellner and associates in sections of 16S RNA designated P, E, E', and K, and one-half the large oligonucleotides of section A. The other large fragment is about 300 nucleotides long and contains the oligonucleotides found in sections C, C', C''. The isolation of these large fragments seems to confirm the arrangement of sections within 16S RNA. There are also recovered from nuclease-treated ribosomes three small fragments, one (120 nucleotides long) from the 5' end, one (26 nucleotides long) from the 3' OH end of the chain, and another section (66 nucleotides long) from the middle of the 16S RNA chain. Small molecular weight material is also generated by nuclease treatment, and about half this material is derived from a region close to the 3' OH end of the 16S RNA chain. This indicates that the most accessible part of the rRNA of E. coli 30S ribosomes is a region 100 to 150 nucleotides long near the 3' end of the chain. A general scheme is proposed to explain the generation of the various-sized RNA products from the rRNA of the 30S ribosome.

Autoradiography↗