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Biomedical subjects

B Clarke

Publications and source records attributed to B Clarke.

At least 163 records · Page 9Linked to original sources
PubMed1976

Commitment to erythroid differentiation by friend erythroleukemia cells: a stochastic analysis.

A method for the clonal analysis of murine erythroleukemia cells has been developed which allows the precise characterization of the number of progeny produced by each cell and the degree of differentiation of each progeny cell. The potential of almost every cell in the culture can be monitored because a plating efficiency close to 100% has been achieved. The effects of treatment with an inducer of differentiation (DMSO) on the proliferative capacity of the treated cells have been studied with this technique. Cells from a mass culture treated with inducer give rise to colonies of differentiated progeny when subsequently cloned in the absence of inducer. Colonies exhibiting this phenotype represent the progeny of cells committed to the differentiation pathway by treatment with inducer. We observe that the commitment decision limits the subsequent proliferative capacity of the cell to four additional cell divisions. A quantitative analysis suggests that the commitment decision for each cell is made in a stochastic manner. Irreversible commitment to the expression of differentiated functions occurs with discrete probability per cell generation for many cell generations. The value for this probability is a function of the concentration of inducer (DMSO). A correlative biochemical study suggests that an irreversible commitment decision by a significant proportion of the population precedes or accompanies increases in cytoplasmic globin mRNA levels, one of the earliest detectable biochemical markers for erythroid differentiation in this system. A specific kinetic model based on these considerations has been developed to predict clonal phenotypes as a function of time and probability of commitment. Quantitative predictions based on this model are in excellent agreement with experimental observations. The effectiveness of a stochastic model in predicting the behavior of this system is discussed in relation to the stochastic behavior of normal hematopoiesis and the biochemical mechanisms which control these differentiation programs.

Cell Division↗
PubMed1976

Supergenes in polymorphic land snails. I. Partula taeniata.

The general colour of the shell in Partula taeniata is controlled by at least two loci. One of these (C) has a series of six alleles which determine the yellow (Y) and neutral brown (N) series of colours. Alleles for darker colours are dominant to those for lighter colours, but dominance is not always complete. The pink (P) colours are determined by a second locus (P) which modified the expression of the lighter alleles of the C locus. Orangeshell colour segregates with yellow but its allelic relationship is unknown. Colour of the lip is controlled by a locus (L) with pink lip dominant to white lip. The colour of the spire is determined by a locus (S) with dark (N4) spire dominant to light spire. An intermediate spire colour shows the same pattern of inheritance and may represent the effect of another allele. Banding of the shell is dominant to absence of bands, with two loci (B1 and B2) determining the type of banding. An allele at B1 produces the frenata pattern; an allele at B2 produces zonata; together they produce lyra. All the loci for which linkage data are available are linked so strongly that the whole array may be considered a supergene. Self-fertilisation takes place primarily during early reproductive life. About 20 per cent of the young of the first mating of an individual are produced by selfing, but over the whole reproductive span the frequency is only about 2-5 per cent. There is inconclusive evidence for heterozygote advantage of banded individuals.

Alleles↗
PubMed1976

Supergenes in polymorphic land snails. II. Partula suturalis.

The colour and banding of the shell of Partula suturalis are controlled by a single locus (M) with a series of at least six alleles. MX, giving apex as a homozygote, is dominant to MF1, giving frenata, which is dominant to the other alleles. MF2 is similar to MF1 except in its relation with MA. MF2MA produces bisecta and provides a striking example of a heterozygote that is qualitatively different from both homozygotes for the alleles producing it. MA gives atra as a homozygote and is dominant to MC and MS. MC, giving cestata as a homozygote, is recessive to all except MS. MS, giving strigata, is the universal recessive. It is suggested that the locus may be complex. The direction of coiling of the shell is determined by the H locus with HS (sinistrality) dominant to HD (dextrality). The expression of coiling is delayed by one generation, the maternal genotype determining the phenotype of the offspring. M and H are not linked. Self-fertilisation occurs infrequently and non-randomly.

Alleles↗
PubMed1976

Infection in the intensive care unit.

An epidemic of infection associated with Serratia marcescens and other Gram-negative organisms resistant to aminoglycosides and other chemotherapeutic agents occurred in the Intensive Care Unit, and spread to other areas of the hospital. This paper describes the problems of sepsis in the critically ill patient, outlines the occurrence of organisms in the patients concerned in this epidemic, and discusses the policies adopted to control the incidence of life-threatening infection caused by bacteria resistant to all other agents.

Anti-Bacterial Agents↗
PubMed1975

Effects of radial artery cannulation.

A prospective study has been carried out in 40 patients of the effects of radial artery cannulation for monitoring purposes. A Doppler flow meter was used to secure objective evidence of the incidence of thrombosis in the cannulated radial artery. Twenty-two of the 41 arteries cannulated were shown to have undergone thrombosis, and the haemodynamic defect associated with the arterial block persisted in all but two until the time of the patient's discharge from hospital. Thirteen of the 20 hands in which a persistent block was demonstrated developed features of mild ischaemia. In four instances, these were transient, and disappeared within a few days. In the remaining nine hands, however, the features persisted to the time of the patient's discharge from hospital at an average of three weeks from the date of cannulation. The mean cannulation time was 45 hours. Radial artery cannulation carries a definite morbidity, and should not be used unless there is no other reasonable way of obtaining vital information for the management of a critically ill patient.

Adult↗
PubMed1975

The contribution of ecological genetics to evolutionary theory: detecting the direct effects of natural selection on particular polymorphic loci.

It is possible to define a strategy for experimentally demonstrating that natural selection acts directly on a particular polymorphic locus, rather than on other loci in linkage disequilibrium with it. This strategy has been applied to the alcohol dehydrogenase polymorphism of Drosophila melanogaster and has provided very strong evidence that the polymorphism is directly subject to selection. It is equally applicable to other polymorphisms and offers the hope of resolving the long-standing debate about the causes of enzyme variation.

Alcohol Oxidoreductases↗