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Biomedical subjects

L K White

Publications and source records attributed to L K White.

14 recordsLinked to original sources
PubMed2001

Telomerase inhibitors.

There has been a vast increase in telomerase research over the past several years, with many different pre-clinical approaches being tested for inhibiting the activity of this enzyme as a novel therapeutic modality to treat malignancy. In this review, we will provide some basic background information about telomeres and telomerase and then discuss the pros, cons and challenges of the approaches that are currently under investigation, and what we might expect in the future of this emerging field.

Animals↗
PubMed1990

Intrastriatal infusions of ascorbate antagonize the behavioral response to amphetamine.

Compared to saline, bilateral infusions of ascorbate (AA) into the neostriatum of freely moving rats attenuated rearing, head bobbing, and sniffing at various times after systemic amphetamine administration. Comparable AA infusions into overlying cerebral cortex failed to alter the amphetamine behavioral response. Intrastriatal AA also enhanced the ability of haloperidol to antagonize amphetamine-induced forepaw shuffling and locomotion. Voltammetric measurements in separate animals revealed a linear increase in neostriatal AA that remained within reasonable physiological limits over the course of the AA infusion. Thus, endogenous AA may modulate behavior via mechanisms intrinsic to the neostriatum.

Administration, Intranasal↗
PubMed1988

Ascorbate antagonizes the behavioral effects of amphetamine by a central mechanism.

The behavioral response to amphetamine was monitored in rats that received simultaneous intraventricular infusions of saline or ascorbate. Both groups of animals displayed comparable responses, although ascorbate significantly delayed the onset of amphetamine-induced locomotion and rearing. In rats pretreated with a threshold dose of haloperidol (0.025 mg/kg), virtually all aspects of the amphetamine response were attenuated, and this effect was enhanced by ascorbate. In haloperidol-pretreated rats, ascorbate significantly lowered sniffing and forepaw shuffling throughout the amphetamine response. These results suggest that ascorbate antagonizes dopaminergic transmission by a central mechanism.

Amphetamine↗
PubMed1988

Identifying reinforcers for persons with profound handicaps: staff opinion versus systematic assessment of preferences.

We evaluated a systematic means of determining stimulus preferences among seven profoundly handicapped persons. Preferences were determined by observing student approach responses to individual stimuli. Results indicated that there were differential stimulus preferences across the multiply handicapped participants. However, results of the systematic assessment did not coincide with the results of a more traditional, caregiver-opinion method of assessing student preferences. A second experiment was then conducted with five participants to evaluate whether stimuli that were assessed to consistently represent preferences would function as reinforcers in skill training programs. Results indicated that stimuli that were systematically assessed to represent student preferences typically functioned as reinforcers when applied contingently. However, preferred stimuli as reflected by caregiver opinion did not function as reinforcers unless those stimuli were also preferred on the systematic assessment. Results are discussed in terms of assisting profoundly handicapped persons by (a) improving the effectiveness of training programs by increasing the likelihood of using stimuli that have reinforcing value and (b) increasing the overall quality of life by providing preferred stimuli in the routine living environment.

Adolescent↗
PubMed1986

Synthesis of a functional F0 sector of the Escherichia coli H+-ATPase does not require synthesis of the alpha or beta subunits of F1.

The uncB, E, F, and H genes of the Escherichia coli unc operon were cloned behind the lac promoter of plasmid pUC9, generating plasmid pBP101. These unc loci code, respectively, for the chi, omega, and psi subunits of the F0 sector and the delta subunit of the F1 sector of the H+-ATP synthase complex. Induction of expression of the four unc genes by the addition of isopropyl-beta-D-thiogalactoside resulted in inhibition of growth. During isopropyl-beta-D-thiogalactoside induction, the three subunits of F0 were integrated into the cytoplasmic membrane with a resultant increase in H+ permeability. A functional F0 was formed from plasmid pBP101 in a genetic background lacking all eight of the unc structural genes coding the F1F0 complex. In the unc deletion background, a reasonable correlation was observed between the amount of F0 incorporated into the membrane and the function measured, i.e., high-affinity binding of F1 and rate of F0-mediated H+ translocation. This correlation indicates that most or all of the F0 assembled in the membrane is active. Although the F0 assembled under these conditions binds F1, only partial restoration of NADH-dependent or ATP-dependent quenching of quinacrine fluorescence was observed with these membranes. Proteolysis of a fraction of the psi subunit may account for this partial deficiency. The experiments described demonstrate that a functional F0 can be assembled in vivo in E. coli strains lacking genes for the alpha, beta, gamma, and epsilon subunits of F1.

Bacterial Proteins↗
PubMed1986

Divorce and marital instability over the life course.

"This study uses a [U.S.] national sample of married persons under age 55, interviewed in 1980 and again in 1983, to estimate why divorce and marital instability vary by age and duration of marriage. Results indicate that the accumulation of assets substantially reduces the propensity to divorce. We also find that several important correlates of divorce and instability (age at marriage, health, social integration, and income) interact with age and duration. In general, these factors seem to operate almost exclusively among young people and young marriages."

Age Factors↗
PubMed1985

H+-ATPase of Escherichia coli. An uncE mutation impairing coupling between F1 and Fo but not Fo-mediated H+ translocation.

The uncE114 mutation from Escherichia coli strain KI1 (Nieuwenhuis, F. J. R. M., Kanner, B. I., Gutnick, D. L., Postma, P. W., and Van Dam, K. (1973) Biochim. Biophys. Acta 325, 62-71) was characterized after transfer to a new genetic background. A defective H+-ATPase complex is formed in strains carrying the mutation. Based upon the genetic complementation pattern of other unc mutants by a lambda uncE114 transducing phage, and complementation of uncE114 recipients by an uncE+ plasmid (pCP35), the mutation was concluded to lie in the uncE gene. The uncE gene codes for the omega subunit ("dicyclohexylcarbodiimide binding protein") of the H+-ATPase complex. The mutation was defined by sequencing the mutant gene. The G----C transversion found results in a substitution of Glu for Gln at position 42 of the omega subunit in the Fo sector of the H+-ATPase. The substitution did not significantly impair H+ translocation by Fo or affect inhibition of H+ translocation by dicyclohexylcarbodiimide. Wild-type F1 was bound by uncE114 Fo with near normal affinity, but the functional coupling between F1 and Fo was disrupted. The uncoupling was indicated by an H+-leaky membrane, even when saturating levels of wild-type F1 were bound. Disassociation of F1 from Fo under conditions of assay did partially contribute to the H+ leakiness, but the major contributor to the high H+ conductance was Fo with bound F1. The F1 bound to uncE114 membranes exhibited normal ATPase activity, but ATP hydrolysis was uncoupled from H+ translocation and was resistant to inhibition by dicyclohexylcarbodiimide. The F1 isolated from the uncE114 mutant was modified with partial loss of coupling function. However, this modification did not account for the uncoupled properties of the mutant Fo described above, since these properties were retained after reconstitution of mutant membrane (Fo) with wild-type F1.

Alleles↗
PubMed1985

Ascorbic acid and the behavioral response to haloperidol: implications for the action of antipsychotic drugs.

Haloperidol, a widely used antipsychotic drug, was tested for its ability to block the behavioral response to amphetamine and to elicit catalepsy in rats treated with saline or ascorbic acid (1000 milligrams per kilogram of body weight). By itself, ascorbic acid failed to exert significant behavioral effects, but it enhanced the antiamphetamine and cataleptogenic effects of haloperidol (0.1 or 0.5 milligrams per kilogram). These results, combined with a growing body of biochemical evidence, suggest that ascorbic acid plays an important role in modulating the behavioral effects of haloperidol and related antipsychotic drugs.

Animals↗
PubMed1984

Mutations altering aspartyl-61 of the omega subunit (uncE protein) of Escherichia coli H+ -ATPase differ in effect on coupled ATP hydrolysis.

Mutations in the H+-translocating ATPase complex (F1F0) of Escherichia coli have been described in which aspartyl-61 of the omega subunit ( uncE protein) is substituted by either glycine ( uncE105 ) or asparagine ( uncE107 ). Either substitution blocks the H+-translocation activity of the F0 sector of the complex. Here we report a difference in the effects of the two substitutions on the coupled ATPase activity of F1 bound to F0. Wild-type F1 was bound to the F0 of either mutant with affinities comparable to wild-type. The ATPase activity of F1 bound to uncE107 F0 was inhibited by 50%, whereas that bound to uncE105 F0 was not inhibited. Complementation studies with a pBR322-derived plasmid that carried the E gene of the unc operon only indicated that a single mutation in the host strain was responsible for the respective phenotypes. In mutants complemented by the uncE + plasmid, restoration of wild-type biochemical properties was only partial and may be attributed to a mixing of wild-type and mutant omega subunits in a hybrid F0 complex. The activity of membrane-bound F1 was less inhibited in the uncE +/ uncE107 hybrid. Paradoxically, complementation of uncE105 by the uncE + plasmid resulted in substantial inhibition of the activity of membrane-bound F1. The results indicate that a glycine-versus-asparagine substitution for aspartyl-61 must lead to altered conformations of omega and that these differences in conformation are important in the coupling between the F0 and F1 sectors of the complex.

Adenosine Triphosphate↗
PubMed1981

A note on racial differences in the effect of female economic opportunity on marriage rates.

The previously observed aggregate relationship between marriage rates and female work opportunities is not found among black Americans. Alternative definitions of family formation which take illegitimacy into consideration are explored and also found to be unrelated to black females' economic opportunities. Although some of the difference may be attributed to measurement error, the significant disparity between the two populations probably reflects substantive differences.

Adolescent↗
PubMed1977

Metal site conformational states of vanadyl(IV) human serotransferrin complexes.

This study was undertaken to investigate the conformational states of the two metal sites in the human serum transferrin molecule. The 9.2 GHz electron paramagnetic resonance spectra of frozen solutions of divanadyl(IV) transferrin consist of a superposition of two sets of resonances, A and B, due to the magnetically nonequivalent binding environments of the VO2+ ion. Examination of the intensities of the A and B resonances as a function of pH from 6.0 to 10.7 reveals that they arise from two conformational states of the metal sites in which the geometrical arrangement and/or identity of one or more ligands in the first coordination sphere are different. From pH 7.5 to 9.0, the metal sites exist in A and B conformations but above pH 9.0 the A conformation. This transformation is coupled to the ionization of an apparently noncoordinating protein functional group with a pK - 10.0 +/- 0.1. Below pH 7.0, binding in the B conformation is rapidly lost, driven in part by the protonation of a functional group, possibly the anion, with a pK - 6.6 +/- 0.1. In 90% D2O, this pK is elevated to 7.8 +/- 0.1. At pH 6.0 in H2O, essentially one VO2+ ion remains bound to the protein with the metal site in the A conformation. Experiments with mixed VO2+ -Fe3+ transferrin complexes indicate that the same may be true of Fe3+. At pH 10.7, a new set of VO2+ resonances, labeled C, are observed; they possibly arise from a third conformation of the metal site. One bicarbonate or corbonate is required per VO2+ ion bound to the protein. 2.7 H+ are released per VO2+ bound in either the A or B conformations. The above results are discussed in terms of the "equivalence" and "nonequivalence" of the metal sites.

Bicarbonates↗