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Biomedical subjects

A Hastings

Publications and source records attributed to A Hastings.

17 recordsLinked to original sources
PubMed1992

Novel vectors for the expression of antibody molecules using variable regions generated by polymerase chain reaction.

A new family of vectors has been produced which facilitates the cloning and expression of immunoglobulin variable regions cloned by polymerase chain reaction (PCR). The vectors are designed to express the cloned variable regions joined to human constant regions and take advantage of priming in the leader sequence so that no amino acid changes will be introduced into the mature antibody molecule. Both the heavy chain and light chain vectors utilize a murine VH promoter provided with an EcoRV restriction site so that the amplified variable regions can be directly cloned into a functional promoter. For the heavy chain an NheI restriction site has been generated at the first two amino acids of CH1 and the cloned leader and variable region are fused directly to the CH1 domain of the constant region. When the leader and variable regions of the light chain were fused directly to C kappa, no expression was observed. Therefore the light chain expression vector was designed with a SalI restriction site for cloning into a splice junction 3' of the variable region; VL then is joined to C kappa by splicing. Both vectors direct the expression of functional, fully assembled immunoglobulin molecules with the expected molecular weight. Use of redundant oligomers to prime the PCR permits the cloning and expression of recombinant antibodies without any prior information as to their sequence and makes it possible to rapidly generate recombinant antibodies from any monoclonal antibody producing cell line.

Animals↗
PubMed1992

Production and characterization of a murine/human chimeric anti-idiotype antibody that mimics ganglioside.

The VL and VH from a murine anti-idiotypic antibody that mimics ganglioside have been cloned, sequenced, and expressed as a chimeric mouse/human IgG1 antibody. The chimeric antibody retained a binding specificity indistinguishable from the original murine antibody. The VH was a member of Vgam 3.8 family. The sequences are discussed in terms of ways in which proteins may mimic ganglioside epitopes.

Amino Acid Sequence↗
PubMed1992

Second-order approximations for selection coefficients at polygenic loci. II. Pleiotropy.

I determine the second-order approximation for the phenotypic distribution of an arbitrary number of quantitative traits, ignoring the effects of epistasis and linkage disequilibrium, conditioned on the presence of a specified genotype at one underlying locus of small effect. Using this approximation, I determine formulae for the effects of selection at a single locus with random mating under either Gaussian stabilizing selection, or correlated selection with truncation selection for one character. These formulae apply for arbitrary phenotypic distributions, yet even with multivariate Gaussian distributions of phenotypic effects the formula for correlated selection includes a correction to the standard formula in Falconer (1989). I demonstrate that this approximation has an error that is third order in the allelic or genotypic effects, independent of the form of the phenotypic distribution. I show also that the approximation of analogous form for the phenotypic distribution conditioned on the presence of a specified allele at a single locus is also correct to second order. Both approximations allow for dominance and are consistent in the sense that computing marginal fitnesses from approximations based on genotypic deviations and those based on average allelic effect yield the same answers.

Genotype↗
PubMed1992

Inferring selective history from multilocus frequency data: Wright meets the Hamiltonian.

We describe a method to study characteristics of the dynamics of multilocus population genetic models without specifying the form of selection a priori. Our approach consists of specifying initial and final genotypic frequencies (either completely or partially) and then determining the minimum time to go from the initial condition to the final condition according to a continuous time genetic model, with arbitrary constraints on the strength and possibly the form of selection. In analyzing a two-locus, two-allele model with this approach, we show that--so long as r is not much larger than s--substantial linkage disequilibrium can be generated from an initial state of linkage equilibrium in a few hundred generations. We also show that unless recombination is much larger than selection, there is only weak dependence on r of the minimum time to reach a specified state. Thus, similar strengths of selection can lead to similar levels of disequilibrium over a fixed time and a range of small recombination rates. This implies that, within the level of a single gene, selection cannot in general be assumed to lead to any particular relationship between recombination rate and levels of disequilibrium. We indicate a number of other ways in which our method can be useful in asking theoretical questions and in interpreting data.

Alleles↗
PubMed1991

The relationship between neuropsychological measures and self-care skills in patients with cerebrovascular lesions.

The present investigation examined the relationship between performance on the Michigan Neuropsychological Battery (MNB) and selected self-care skills in a group of patients with unilateral cerebrovascular lesions. Among MNB measures, left-sided somatosensory and motor functions were the best predictors of self-care skills, showing that in these stroke patients lower level cerebral functions mediated by the right hemisphere are more strongly related to the self-care skills examined than higher cerebral functions. Also, evidence that patients with cerebrovascular lesions in the left hemisphere performed better than patients with right hemisphere lesions in several self-care categories is further indication that right hemisphere processes have a special role to play in the mediation of these self-care activities. The research and clinical implications of these findings are noted.

Activities of Daily Living↗
PubMed1991

Neuropsychological studies of blacks with cerebrovascular disorders: a preliminary investigation.

Very few studies have been conducted that examine brain behavior functions in blacks and other ethnic minorities. Recognizing that measures of higher cortical functions have cultural, experiential, and organic determinants, the present investigation was designed to ascertain whether findings reported in neuropsychologic studies of white patients with lateralized cerebral lesions are applicable to groups of black patients with lesions in similar locations. Thirty-seven patients with left (n = 15) and right (n = 22) cerebrovascular lesions were administered the Michigan Neuropsychological Battery (MNB). This battery is comprised of a number of objective standardized measures of higher and lower-level cerebral functions. With one exception, the performance of patients in the brain-injured groups was not systematically different on tests of higher brain functions. As expected, tests of lower-level somatosensory and motor functions showed a pattern of greater impairment on the side of the body contralateral to the lesion. But, in contrast to neuropsychological studies of white patients, a pattern of laterality specific deficits on verbal IQ and performance IQ was not observed. Methodological and theoretical implications of these findings are discussed.

Analysis of Variance↗
PubMed1990

Second-order approximations for selection coefficients at polygenic loci.

I determine the second-order approximation for the phenotypic distribution of a quantitative trait, ignoring the effects of epistasis and linkage disequilibrium, conditioned on the presence of a specified genotype at one underlying locus of small effect. I demonstrate that this approximation has an error that is third order in the allelic or genotypic effects, independent of the form of the phenotypic distribution. I also show that the approximation of analogous form for the phenotypic distribution conditioned on the presence of a specified allele at a single locus is also correct to second order. Both approximations allow for dominance and are consistent in the sense that computing marginal fitnesses from approximations based on genotypic deviations and those based on average allelic effect yield the same answers. Surprisingly, the second-order approximations derived here yield the same approximation for dynamics at a single locus as first-order approximations used earlier thus justifying earlier stability computations based on these first-order approximations.

Alleles↗
PubMed1990

Maintenance of polygenic variation through mutation-selection balance: bifurcation analysis of a biallelic model.

Biallelic models which ignore linkage disequilibrium have been used to study variability maintained by mutation in the presence of Gaussian stabilizing selection. Recent work of Barton (1986) showed that these models have stable equilibria at which the mean phenotype differed from the optimum, and that the variability maintained at such equilibria would be higher than at the symmetric equilibria calculated by Bulmer (1980) and others. Here I determine the bifurcation structure of this model, and confirm and extend Barton's results. The form of the bifurcations gives information about the domains of attraction of various equilibria, and shows why the nonsymmetric equilibria may not be observed. The techniques may prove useful in the analysis of other population genetic models.

Alleles↗