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Biomedical subjects

B Clarke

Publications and source records attributed to B Clarke.

At least 145 records · Page 8Linked to original sources

The suitability of immunosuppressed mice kept in a standard animal unit as recipients of human tumour xenografts.

CBA/Lac mice were immunosuppressed by thymectomy and whole body irradiation with 250 kVp X-rays following pretreatment with cytosine arabinoside. The optimum radiation dose for immunosuppression with prolonged survival was 7.35 Gy. The animals were kept in a standard animal unit with an overall survival rate of 83%. They were found to be suitable for large scale, long-term, xenotransplantation experiments at 20% of the cost of nude mice.

Animals↗

Mental illness and rehabilitation in early nineteenth-century Ireland: the case of Charles Stock.

The case of a sixteen-year-old youth is presented on the basis of correspondence over the years 1806 to 1813. His initial breakdown was probably due to hebephrenic schizophrenia, but clinical detail is defective and the evidence is chiefly about the difficulties of recovery and rehabilitation. The case is discussed in relation to the treatment he received and against the background of provision for insanity and psychiatric methods and ideas in Ireland during the period.

Adolescent↗

Radioimmunoassay techniques for the determination of the local release of prostaglandins and thromboxanes.

Radioimmunoassay techniques are described that enable the quantification of the local release of prostaglandin (PG) E2, PGF2 alpha, TxB2 (the metabolite of thromboxane A2), and 6-keto PGF1 alpha (a metabolite of prostacyclin) from various organs in vivo. Plasma samples were acidified and the prostanoids extracted with ethyl acetate, prior to assay. The mean recovery of tritiated internal standards was 60% for 6-keto PGF1 alpha and 84% for the other prostanoids. Sample extracts were redissolved in phosphate-buffered saline and the appropriate tritiated antigen and specific antibody were added. After overnight incubation the antibody-bound and free prostanoid were separated using dextran-coated charcoal. The intraassay variation and the interassay variation were similar for all prostanoids; the mean values being 8.5% and 13.2%, respectively. There were variations in the sensitivity of the radioimmunoassay for each prostanoid. Using 250 microliter plasma samples the detection limit for PGE2 was 75 pg/ml, PGF2 alpha 50 pg/ml, TxB2 25 pg/ml, and 6-keto PGF1 alpha 125 pg/ml. These assays have been used to determine prostanoid concentrations in rats, cats, dogs, and humans.

Antibody Specificity↗

Associations of enzymic and chromosomal polymorphisms in the seaweed fly, Coelopa frigida.

Populations of seaweed fly Coelopa frigida are polymorphic at three loci determining the enzymes peptidase-1 (Pep-1), alcohol dehydrogenase (Adh) and larval esterase-2 (Es-2). Alleles at these loci have been shown by others to be non-randomly associated with each other. In the present paper we report non-random associations between the Adh and Es-2 loci and inversions on chromosome I. The two common alleles Adh-B and D are in strong linkage disequilibrium with the alpha and beta inversions, but the Adh-A and C alleles are not so. The X and Y alleles at the Es-2 locus show weak, but still significant, associations with the inversions. We consider possible linkage relationships of the loci on the chromosomal arrangements, and discuss the hypothesis that they constitute part of a coadapted gene complex whose members code for functionally related enzymes.

Alcohol Oxidoreductases↗

A comparison of the response to hyperthermia of murine haemopoietic stem cells (CFU-S) and L1210 leukaemia cells: enhanced killing of leukaemic cells in presence of normal marrow cells.

When the clonogenic survival of mouse haemopoietic stem cells (CFU-S) and leukaemia L1210 cells growth as ascites tumours are compared after being heated in vitro and assayed in vivo by spleen-colony assay, there is no significant difference in the terminal slopes of the survival curves. The shoulders of the survival curves differ, but this may be explained by differences in cell kinetics. By contrast, L1210 leukaemic marrow cells are considerably more susceptible to the lethal effects of hyperthermia (43 degrees C) than either normal marrow stem cells or L1210 leukaemic cells grown as ascites tumours. Moreover, the killing of L1210 ascites cells by hyperthermia can be enhanced by heating L1210 ascites cells with an equal number of normal marrow cells, or as upernatant removed from heated marrow cells. Most cells in lukaemic marrow are normal, and it is postulated that the increased thermal sensitivity of L1210 cells in leukaemic marrow is caused by diffusible factors (e.g. lysosomal enzymes) released by heating normal marrow cells.

Animals↗

Selection associated with the alcohol dehydrogenase locus in Drosophila melanogaster: differential survival of adults maintained on low concentrations of ethanol.

David and his collaborators have reported that adult Drosophila melanogaster survive longer on 2 per cent ethanol than on distilled water, but that the increased survival on ethanol does not occur in mutant flies lacking alcohol dehydrogenase activity. This has led us to enquire if the polymorphic alleles at the alcohol dehydrogenase locus (AdhF and AdhS), which code for enzymes with different activities, affect survival on low concentrations of ethanol. Flies were kept in sealed glass chambers containing either 2 per cent ethanol or distilled water. In four experiments, comprising a total of 126 replicates, the proportion of surviving FF flies, relative to SS, was greater on ethanol than on water. In two experiments the excess was highly significant. It appears that FF flies are better able than SS to use ethanol as food. Our results support the view that selection acts directly on the Adh polymorphism.

Alcohol Oxidoreductases↗

The construction of a recombinant cDNA library representative of the poly(A)+ mRNA population from normal human lymphocytes.

A recombinant library has been constructed using the plasmid pAT153 and double stranded cDNA prepared from normal human lymphocyte poly(A)+ RNA. Transformation conditions were optimized to yield approximately 200,000 recombinants per microgram of double stranded cDNA. Statistical analysis as well as sequence complexity analysis of the inserted sequences indicates that the cDNA library is representative of > 99% of the poly(A)+ RNA present in the normal human lymphocyte.

Base Sequence↗

Human erythroid burst-forming unit: T-cell requirement for proliferation in vitro.

Human mononuclear leukocytes were fractionated into populations of null, T and B cells by immunoabsorbent column chromatography followed by E-rosette formation and purification of T cells by differential centrifugation and osmotic lysis. The unfractionated and fractionated cell populations were first separately cultured for 14 days in plasma clots in the presence of two international units erythropoietin. Typical erythroid burst-forming unit (BFU-E)-derived colonies grew in the unfractionated cell cultures but not from T- or B-cell cultures. BFU-E colonies grew in null cell cultures but most of the colonies were small and variably hemoglobinized with less than three subcolonies. When intact T cells were added to null cells and cocultured, many typical large BFU-E colonies with more than 10 well homogenized subcolonies appeared. Increasing numbers of large BFU-E colonies in null cell cultures were induced by stepwise addition of T cells but not by the addition of B cells. A conditioned medium in which T cells had been induced to divide by tetanus toxoid substituted for intact T cells in this T-cell-dependent BFU-E colony formation observed in null cells. These findings demonstrate that the BFU-E, a committeded erythroid stem cell, resides in the null cell fraction of peripheral blood, but its proliferative capacity and differentiation in vitro requires a soluble product of T cells. Such experiments now permit a new approach to the assessment of various disorders of erythropoiesis. Erythroid hypoplasia in a particular case may be due to dysfunction of the committed precursor cell or to a failure of a helper effect induced by T cells.

B-Lymphocytes↗

Studies of globin chain synthesis and globin mRNA content in a patient homozygous for hemoglobin Lepore.

Globin chain synthesis and globin mRNA content were studied in blood cells of a patient homozygous for Hb Lepore. Peripheral blood cells incubated with tritiated leucine synthesized approximately 1.5 to 3% as many Lepore globin chains as alpha chains. Globin mRNA in peripheral blood cell RNA was assayed by molecular hybridization assays using human alpha and beta cDNA, and the results indicated the presence of approximately 1% to 2% as much beta-like mRNA (presumably deltabeta Lepore mRNA) as alpha mRNA. The amount of Lepore deltabeta chain mRNA in peripheral blood cells is therefore proportional to the amount of Lepore globin chain synthesis in the same cells. An incidental observation was the finding that peripheral blood cell RNA of this patient, at a time when she was being heavily transfused, contained substantially higher levels of beta-like mRNA (relative to alpha mRNA) than in subsequent studies. Cell-free translation of this mRNA however revealed that it contained authentic beta chain mRNA which must have been derived in some way from the transfused blood cells.

Child↗