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Biomedical subjects

G Lowe

Publications and source records attributed to G Lowe.

At least 19 recordsLinked to original sources
PubMed1997

Presence of t(8;21)(q22;q22) in myeloperoxidase-positive, myeloid surface antigen-negative acute myeloid leukemia.

Although acute myeloid leukemias (AMLs) cytochemically negative for myeloperoxidase are now well recognized, myeloid surface antigen-negative AMLs are rare. The morphologic, cytochemical, immunologic, and cytogenetic or molecular features of such cases are described in four adults aged 19 to 60 years. All had AML with maturation (FAB M2) and were myeloperoxidase positive. Immunologic studies showed all to be HLA-DR positive but negative for the CD13, CD14, and CD33 antigens. Two of four were CD34 antigen positive. Cytogenetic studies were performed in three patients, and all demonstrated t(8;21)(q22;q22). In studies using the reverse transcriptase polymerase chain reaction in two patients, including the patient in whom karytypic analysis was not performed, the AML1-ETO fusion product of t(8;21) was identified. These findings suggest an association between the lack of myeloid antigen expression in myeloperoxidase-positive AML and the presence of t(8;21). In addition, the results demonstrate the continued need for cytochemical studies in the evaluation of acute leukemias.

Adult↗
PubMed1996

An investigation of the binding of protein proteinase inhibitors to trypsin by electrospray ionization mass spectrometry.

The binding of BPTI and SBTI with trypsin has been investigated by ESI MS, using the mutant K15V-BPTI and the chemically modified RcamBPTI as controls. Although high cone voltages (+80 V) produce sharp spectra of BPTI, RcamBPTI, SBTI and trypsin alone, the complexes of BPTI, RcamBPTI and SBTI with trypsin undergo partial dissociation due to collisional activation. At lower cone voltages (+40 V) these non-covalent complexes are stable. The charge distribution on the trypsin and the inhibitors produced by gas phase dissociation of the complexes are markedly different from those of the components alone, indicating that ESI MS provides a novel probe for exploring the ionic interactions at the contact surface of proteins. Moreover, by determining the cone voltage at which the gas phase dissociation of complexes occurs it may be possible to use ESI MS to compare the binding energies of closely related complexes.

Acetates↗
PubMed1996

Inhibition of human leukocyte and porcine pancreatic elastase by homologues of bovine pancreatic trypsin inhibitor.

The interactions of three BPTI homologues with human leukocyte elastase and porcine pancreatic elastase have been investigated. The principal mutation in determining the specificity of inhibition was the Lys15-Val mutation at the P1 position. An additional mutation at P3, i.e., BPTI (Lys15-Val, Pro13-Ile), increased the inhibition of HLE to a Ki = 2.5 x 10(-10) M, but decreased the inhibition of PPE, showing this to be a useful site for improving selectivity. Kinetic evidence suggests that the inhibition of HLE by BPTI homologues probably takes place by a two-step mechanism in which an isomerization step occurs after initial binding. 1H NMR spectroscopy of the BPTI (Lys15-Val) and BPTI (Lys15-Val, Pro13-Ile) mutants indicates that small conformational changes are associated with the mutations, but these are localized in the immediate vicinity of the mutation in the outer binding loop and in the inner loop connected to it through the Cys14-Cys38 disulfide bridge.

Amino Acid Sequence↗
PubMed1996

The structure of 4-way DNA junctions: specific binding of bis-intercalators with rigid linkers.

During replication and recombination, two DNA duplexes lie side by side. We have developed reagents that might be used to probe structure during these critical processes; they contain two intercalating groups connected by a rigid linker that forces those groups to point in opposite directions. If their stereochemistry proves appropriate, such structure-specific agents should intercalate specifically into adjacent duplexes in the Y- and X-shaped structures (i.e. 3- and 4-way junctions, now known as 3H and 4H junctions) found at replication and recombination sites. We prepared DNA structures in which four duplexes were arranged in all possible combinations around 2- and 4-way junctions and then probed the accessibility to DNase I of all their phosphodiester bonds. In the absence of any bis-intercalators, 7-9 nucleotides (nt) in each of the strands in 4-way junctions were protected from attack; protected regions were significantly offset to the 3' side of the junction in continuous strands, but only slightly offset, if at all, in exchanging strands. All the intercalators decreased accessibility throughout the structure, but none did so at specific points in the two adjacent arms of 4-way junctions. However, one bis-intercalator--but not its sister with a shorter linker--strikingly increased access to a particular CpT bond that lay 9 nt away from the centre of some 4-way junctions without reducing access to neighbouring bonds. Binding was both sequence and structure specific, and depended on complementary stereochemistry between bis-intercalator and junction.

Acridines↗
PubMed1996

4-Picoline-2,2':6',2"-terpyridine-platinum(II) - a potent intercalator of DNA.

4-Picoloine-2,2':6',2"-terpyridine-platinum(II) is shown in a ligation assay to unwind and so intercalate into DNA. Circular dichroism is used to determine an equilibrium binding constant of approximately 2 x 10(7) M(-1) for the most stable binding mode of 4-picoline-2,2':6',2"-terpyridine-platinum(II) to poly[d(A-T)2] with a site size of about 4 base pairs, and about 1 x 10(6) M(-1) for a second binding mode with a site size of about 2 base pairs. Fluorescence spectroscopy provides further evidence for the strong equilibrium binding constant of 4-picoline-2,2':6',2"-terpyridine-platinum(II) in that it displaces ethidium bromide bound to DNA. The double positive charge on 4-picoline-2,2':6',2"-terpyridine-platinum(II), together with the intercalative binding mode is probably responsible for the large binding constant.

Binding Sites↗
PubMed1996

Diffusion through narrow pores: movement of ions, water and nonelectrolytes through track-etched PETP membranes.

The rates at which ions (86Rb+, [3H]-choline, 36Cl), 3H2O and nonelectrolytes ([14C]-urea, [14C]-glycerol, and [14C]-sugars) equilibrate across track-etched polyethyleneterephthalate (PETP) membranes (isotopic diffusion) have been measured by a 'static' and a 'dynamic' technique under conditions where no net flow takes place; the two techniques give essentially the same results. All tracers diffuse faster the longer the membranes are etched, consistent with an increase in pore size. Water and neutral solutes diffuse at rates that are relatively independent of ionic strength, pH or the presence of divalent cations. Diffusion of cations is decreased by high ionic strength, by reducing pH or by addition of divalent cations; diffusion of chloride is increased by these procedures. Treatment of the membrane with diazomethane to reduce the negative fixed charge decreases diffusion of cations and increases that of anions; diffusion of water and neutral solutes is unaffected by methylation except in the membranes with the narrowest pores (i.e., those etched for the shortest time), in which case diffusion is reduced. We conclude (1) that the special features of flow near a charged surface apply to ions but not to water or nonelectrolytes and (2) that calculation of absolute rates of diffusion leads to values for the radii of pores through track-etched PETP membranes that are in remarkably good agreement with measured values.

Anions↗
PubMed1996

A mass spectrometric investigation of the reaction between 4,4'-vinylenedipyridine bis[2,2':6',2"-terpyridine platinum(II)] and the self-complementary oligonucleotide d(CpGpTpApCpG).

4,4'-Vinylenedipyridine bis[2,2':6',2"-terpyridine platinum(II)], a potential intermolecular bis-intercalator of DNA, reacts slowly at PtII, the linker being displaced by nucleobases. Crystallization of 4,4'-vinylenedipyridine bis[2,2':6',2"-terpyridine platinum(II)] in the presence of the self-complementary oligonucleotide d(CpGpTpApCpG) gave a product which was analyzed by electrospray ionization mass spectrometry. Molecular mass measurements demonstrated ligation of one terpyridine PtII, which was shown by liquid chromatography-mass spectrometry to reside exclusively on deoxyguanosine. The terpyridine PtII was shown by tandem mass spectrometry to be attached to the 3'-terminal deoxyguanosine, consistent with N-7 substitution.

2,2'-Dipyridyl↗
PubMed1996

The effect of oral vanadyl sulfate on body composition and performance in weight-training athletes.

The effects of oral vanadyl sulfate (VOSO4) (0.5 mg/kg/day) on anthropometry, body composition, and performance were investigated in a 12-week, double-blind, placebo-controlled trial involving weight-training volunteers. Performance was assessed in the treatment (VS) and placebo (P) groups using 1 and 10 repetitions maximum (RM) for the bench press and leg extension. Thirty-one subjects completed the trial, with 2 VS subjects withdrawing because of apparent side effects. There were no significant treatment effects for anthropometric parameters and body composition during the trial. Both groups had significant improvements in performance but the only significant effect of treatment was a Treatment x Time interaction in the 1 RM leg extension (p = .002), which could have arisen because the VS group had a lower performance at baseline in this test. It was concluded that oral vanadyl sulfate was ineffective in changing body composition in weight-training athletes, and any modest performance-enhancing effect requires further investigation.

Absorptiometry, Photon↗
PubMed1995

Olfactory transduction is intrinsically noisy.

The sources of noise that limit olfactory signal detection were investigated in dissociated rat olfactory receptor cells. Near-threshold odorant-evoked currents exhibited large random fluctuation. However, similar fluctuations were observed in the absence of applied odorants when currents were induced by elevating the intracellular cyclic AMP concentration. This suggests that the fluctuations reflect noise intrinsic to the transduction mechanism, rather than the quantal nature of an odorant stimulus. For many odorants, this intrinsic noise may preclude the reliable detection of single odorant molecules.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Judgments of substance use and creativity in 'ordinary' people's everyday lifestyles.

To investigate the relationship between substance use and creativity, four pairs of raters independently assessed the reports of over 600 respondents from the Mass-Observation (M-O) Archive. The M-O directive addressed, their use of 'stimulants and relaxants.' Correlations between 'creativity' ratings and 'substance use' ratings were low but significantly positive (around .275). The observed links are discussed in relation to laboratory-based and other studies of substance use and creativity.

Adolescent↗
PubMed1995

Production of bovine-pancreatic-trypsin-inhibitor homologues in Escherichia coli and their characterization.

Biologically active bovine pancreatic trypsin inhibitor (BPTI) was produced in Escherichia coli using an OmpA leader-peptide fusion-protein system, and BPTI homologues were generated by cassette mutagenesis. Amino acids in the reactive loop of alpha 1-proteinase inhibitor (alpha 1-PI) were incorporated into the reactive loop of BPTI in a stepwise approach such that the contribution of individual amino acids could be assessed. The introduction of mutations into BPTI diminished the yield of heterologous protein relative to wild-type BPTI. However, for three BPTI homologues sufficient material was isolated to allow characterization of the proteins by electrospray MS and N-terminal peptide sequencing.

Amino Acids↗
PubMed1995

Teenage drinking: a 4-year comparative study.

Two adolescent drinking surveys carried out within 4 years in the same region of the UK were compared on three aspects of drinking behaviour. The results showed that there was a higher proportion of non-drinkers in 1992 as compared with 1988 for males aged 11-15 and females aged 11-13; more 11-13 year-old females in 1992 reported their home as the location of their first alcoholic drink without their parents; and younger boys were less likely, in 1992, to report ever being drunk. The relative increase in the proportion of non-drinking adolescents is in line with similar recent trends in national sample surveys of young adults.

Adolescent↗
PubMed1994

Crystal structure of the mutant D52S hen egg white lysozyme with an oligosaccharide product.

The crystal structure of a mutant hen egg white lysozyme, in which the key catalytic residue aspartic acid 52 has been changed to a serine residue (D52S HEWL), has been determined and refined to a crystallographic R value of 0.173 for all data F > 0 between 8 and 1.9 A resolution. The D52S HEWL structure is very similar to the native HEWL structure (r.m.s. deviation of main-chain atoms 0.20 A). Small shifts that result from the change in hydrogen bonding pattern on substitution of Asp by Ser were observed in the loop between beta-strands in the region of residues 46 to 49. D52S HEWL exhibits less than 1% activity against the bacterial cell wall substrate. Cocrystallisation experiments with the hexasaccharide substrate beta(1-4) polymer of N-acetyl-D-glucosamine (GlcNAc6) resulted in crystals between 5 days and 14 days after the initial mixing of enzyme and substrate. Analysis by laser absorption mass spectrometry of the oligosaccharides present after incubation with native and D52S HEWL under conditions similar to those used for crystal growth showed that after 14 days with native HEWL complete catalysis to GlcNAc3. GlcNAc2 and GlcNac had occurred but with D52S HEWL only partial catalysis to the major products GlcNAc4 and GlcNAc2 had occurred and at least 50% of the GlcNAc6 remained intact. X-ray analysis of the D52S-oligosaccharide complex crystals showed that they contained the product GlcNAc4. The structure of the D52S HEWL-GlcNAc4 complex has been determined and refined to an R value of 0.160 for data between 8 and 2 A resolution. GlcNAc4 occupies sites A to D in the active site cleft. Careful refinement and examination of 2Fo-Fc electron density maps showed that the sugar in site D has the sofa conformation, a conformation previously observed with the HEWL complex with tetra-N-acetylglucosamine lactone transition state analogue, the HEWL complex with the cell wall trisaccharide and the phage T4 lysozyme complex with a cell wall product. The semi-axial C(5)-C(6) geometry of the sofa is stabilised by hydrogen bonds from the O-6 hydroxyl group to the main-chain N of Val109 and main-chain O of Ala107. The sugar in site D adopts the alpha configuration, seemingly in conflict with the observation that the hydrolysis of beta (1-4) glycosidie linkage by HEWL proceeds with 99.9% retention of beta-configuration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Suppression of odorant responses by odorants in olfactory receptor cells.

Odorants activate an inward current in vertebrate olfactory receptor cells. Here it is shown, in receptor cells from the newt, that odorants can also suppress this current, by a mechanism that is distinct from inhibition and adaptation. Suppression provides a simple explanation for two seemingly unrelated phenomena: the anomalously long latency of olfactory transduction and the existence of an "off response" at the end of a prolonged stimulus. Suppression may influence the perception of odorants by masking odorant responses and by sharpening the odorant specificities of single cells.

Acetophenones↗
PubMed1994

The closure of a long-stay psychiatric hospital: a longitudinal study of patients' behavior.

This paper summarises longitudinal data based on repeat assessments of the behavioural functioning of 90 long-stay psychiatric patients. Data were gathered over a period of 4-5 years that spanned a hospital closure and the resettlement of patients in various alternative settings. Time-series analyses of individual data sets showed that resettlement led to no significant behavioural change in the majority of patients. However, some significant behavioural improvements were evidenced for approximately 20% of the group, while behavioural deterioration occurred in approximately 12%. Supplementary findings showed that following resettlement the quality of care provided significantly improved in many respects. However, access to social, recreational or vocational activities was reduced. In addition, the level of physical health symptomatology was shown to increase for this group of patients.

Aged↗
PubMed1994

Group differences in alcohol-creativity interactions.

A repeated-measures, balanced-order design was used to test for the effects of alcohol on creativity as measured by verbal forms of the Torrance Creativity Test. Social drinkers (8 men and 8 women) performed under 2 conditions, alcohol (dose = 0.83 ml ethanol/kg body weight) and a placebo. Significant group differences in the alcohol-creativity interaction were noted in that the performance of higher-scoring (in the placebo condition) subjects was impaired by alcohol whereas that of lower-scoring subjects was enhanced.

Achievement↗
PubMed1993

Nonlinear amplification by calcium-dependent chloride channels in olfactory receptor cells.

The sense of smell is highly evolved in mammals, allowing discrimination between a vast number of odorants, with detection thresholds as low as 10(-17) M (ref. 1). Although several features of mammalian olfactory transduction have been revealed by biochemical and molecular biological studies, the odorant-induced membrane current has remained elusive. In amphibians this current is mediated by cyclic-nucleotide-gated channels, which depolarize the cell by Na+ and Ca+ influx and consequent Cl- efflux through Ca(2+)-dependent Cl- channels. The Cl- current may be absent in mammals, however, because its proposed role is linked to the aquatic habitat of amphibians. Here we show that the transduction current in rat olfactory receptor cells is initiated by cyclic-nucleotide-gated channels. The Cl- current is also present and endows the transduction current with a steep sigmoidal dependence on cyclic AMP concentration in both rat and in an amphibian, indicating a new function for the Cl- channel: nonlinear amplification of the transduction signal, whereby suprathreshold responses are boosted relative to basal transduction noise.

Amphibians↗