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Biomedical subjects

C Kidson

Publications and source records attributed to C Kidson.

At least 109 records · Page 6Linked to original sources
PubMed1983

Perturbations of cell-cycle progression in gamma-irradiated ataxia telangiectasia and Huntington's disease cells detected by DNA flow cytometric analysis.

The effects of ionizing radiation on cell-cycle progression in lymphoblastoid cell lines derived from ataxia telangiectasia (AT) and Huntington's disease (HD) patients, and from normal individuals, were studied using DNA flow cytometric analysis. A dose of 100 rad gamma irradiation blocked a proportion of normal and HD cells in G1. A higher radiation dose applied to normal cells increased the number of cells blocked in G1 and significantly delayed cells which were in S at the time of irradiation from reaching G2 DNA content. The reduced cumulative mitotic index in irradiated cultures of normal cells 2 h after irradiation suggests that cells in G2 at the time of irradiation are delayed before entering mitosis. After irradiation HD cells responded similarly to normal cells except that a greater proportion of HD cells were blocked in G1. AT cells do not show the normal delay in progression from G1 to S, or from S to G2 in the first cycle after irradiation. The cumulative mitotic index was reduced in irradiated cells, implying that they are delayed in G2. Thus AT cells did not recognize or respond to signals from damaged DNA which in normal and HD cells caused a proportional block in G1 and an S-phase delay. The only point of arrest in cell-cycle progression in irradiated AT cells was in G2.

Ataxia Telangiectasia↗
PubMed1983

Resistance of Melanesian elliptocytes (ovalocytes) to invasion by Plasmodium knowlesi and Plasmodium falciparum malaria parasites in vitro.

Erythrocytes from humans with Melanesian elliptocytosis are resistant to invasion by Plasmodium falciparum in vitro and epidemiological evidence suggests they may be resistant to P. vivax and P. malariae. We have examined the ability of P. knowlesi merozoites to invade Melanesian elliptocytes in vitro as a definitive means of examining these cells for resistance to invasion by malarial species with different receptor requirements. The Melanesian elliptocytes were highly resistant to invasion by P. knowlesi merozoites showing that the resistance associated with this erythrocyte variant lies at a level common to the invasion pathway(s) of P. falciparum and P. knowlesi. This makes Melanesian elliptocytosis unique as no other human erythrocyte variant has been shown to be resistant to invasion by both species.

Elliptocytosis, Hereditary↗
PubMed1982

An automated assay of merozoite invasion of erythrocytes using highly synchronized Plasmodium falciparum cultures.

Plasmodium falciparum cultures were synchronized using three lytic treatments with sorbitol. Schizonts from these cultures were used in a rapid, highly sensitive assay of invasion of erythrocytes by merozoites. The parasitaemias in recipient cells after invasion were determined by flow cytofluorimetry after staining with the dye 33258 Hoechst. Invasion of erythrocytes was shown to be reduced by serum from a patient with malaria. The assay is suitable for rapidly screening large numbers of samples, such as monoclonal antibodies.

Animals↗
PubMed1982

Immunoprecipitation of biosynthetically labelled, stage-specific proteins from cultured Plasmodium falciparum using inhibitory human sera.

Proteins from synchronized continuous cultures of Plasmodium falciparum were biosynthetically labelled with [35S]methionine at ring, trophozoite, and schizont stages. Several proteins appeared to be synthesized predominantly at one stage only, especially the schizont stage. Immunoprecipitation using inhibitory human sera revealed that a variety of proteins, from all stages of parasite growth, were recognized. More proteins, especially those with high molecular weight, were precipitated from the schizont stage than from ring and trophozoite stages, but two major proteins (MW or approximately 70,000 daltons and or approximately 45,000 daltons) were recognized in all three stages.

Animals↗
PubMed1982

Ultraviolet radiation sensitivity of proliferating and differentiated human neuroblastoma cells.

The effects of ultraviolet (U.V.) radiation were studied on a cloned line of human neuroblastoma cells in proliferative and differentiated growth modes, the latter being induced by serum deprivation. The neuroblastoma cells were found to be unusually sensitive in comparison with HeLa cells when survival was measured by colony formation in soft agar, the differentiated mode being the most sensitive. Ultraviolet radiation sensitivity was associated with very low DNA repair capacity as measured by DNA repair synthesis and by removal of M. luteus endonuclease-sensitive sites from irradiated DNA. The greater sensitivity of the differentiated cells appeared to be related to a greater degree of DNA damage at a given U.V. dose, resulting from altered cell geometry in the growth mode. The neuroblastoma cells showed little or no post-irradiation inhibition of DNA replication at low U.V. doses, suggesting that it is the repair process rather than the DNA damage which is responsible for inhibiting replication.

Cell Line↗
PubMed1982

Antigenic differences among isolates of Plasmodium falciparum demonstrated by monoclonal antibodies.

Hybridomas raised against two Papua New Guinea (PNG) isolates of Plasmodium falciparum secreted monoclonal antibodies which bound to schizonts of all seven PNG isolates tested but not to schizonts of four non-PNG isolates from Thailand, Nigeria, Ghana, and The Netherlands. Some of the monoclonal antibodies were tested for their ability to inhibit the growth of one PNG isolate, one Thai isolate, and one Nigerian isolate in vitro. Only the growth of the PNG isolate was inhibited, thus demonstrating functional antigenic differences among isolates of P. falciparum.

Animals↗
PubMed1982

Purification of mature schizonts of Plasmodium falciparum on colloidal silica gradients.

The density of human erythrocytes infected in vitro with Plasmodium falciparum has been measured by isopycnic centrifugation in colloidal silica gradients. The densities of uninfected cells, rings, trophozoites, young schizonts, and mature schizonts were approximately 1.110, 1.110, 1.106, 1.097, and 1.090 g/ml, respectively. This information has been used to design a simple procedure for the separation of schizonts from other parasite stages and uninfected erythrocytes. By using synchronized cultures it is possible to obtain essentially pure schizonts after two centrifugations using a bench centrifuge. Such preparations are an excellent source of parasite antigen for immunological studies.

Centrifugation↗
PubMed1982

Familial melanoma associated with dominant ultraviolet radiation sensitivity.

Sensitivity to ultraviolet radiation was studied in lymphoblastoid cell lines derived from 32 members of two families with histories of multiple primary melanomas in several generations. As assayed by colony formation in agar or by trypan blue exclusion following irradiation, cellular sensitivity showed a bimodal distribution. All persons with melanoma or multiple moles were in the sensitive group, while some family members exhibited responses similar to those of controls. Cells from four cases of sporadic melanoma showed normal levels of sensitivity. The data are consistent with a dominantly inherited ultraviolet light sensitivity associated with these examples of familial melanoma. Spontaneous and ultraviolet light-induced sister chromatid exchange frequencies were similar to those in control cell lines. No defect in excision repair was detected in any of the above cell lines, but the sensitive group showed postirradiation inhibition of DNA replication intermediate between controls and an excision-deficient xeroderma pigmentosum cell line.

Cell Survival↗
PubMed1981

Sensitivity and resistance of human melanoma cells to ultraviolet radiation.

A human melanoma cell line (MM253) was found to be sensitive to ultraviolet (UV) radiation, having a Do of 1.0 J/M2 when cloned on plastic culture dishes and a Do of 2.3 J/m2 when cloned in agar. These figures are much lower than those obtained for all other human melanoma cell lines studied in this laboratory (Do of 32-40 J/m2) and demonstrate that MM253 is unusually UV sensitive. The increased level of UV sensitivity in MM253 is not due to a reduced capacity for excision of pyrimidine dimers, repair of DNA single-strand breaks or elongation of newly-synthesized DNA strands when comparison is made with a UV-resistant melanoma cell line.

Cell Line↗
PubMed1981

Ovalocytic erythrocytes from Melanesians are resistant to invasion by malaria parasites in culture.

Ovalocytic erythrocytes from Melanesians in Papua New Guinea have been demonstrated to be resistant to infection by malaria parasites (Plasmodium falciparum) in culture by using a double-label fluorescence assay of merozoite invasion. That merozoites do not bind irreversibly to ovalocytes has been demonstrated by an assay that measures competition between ovalocytes and normocytes. Analysis of behavior on thermal deformation has demonstrated that ovalocytes are more more thermostable than normocytes, suggesting that there is a major difference in cytoskeletal structure. These findings with P. falciparum and epidemiological data demonstrating clinical resistance to P. vivax and P. malariae suggest that the membrane alterations(s) in these ovalocytes affect(s) invasion step(s) common to all three species of malaria parasite.

Animals↗
PubMed1981

Huntington's disease: implications of associated cellular radiosensitivity.

Ionizing radiation sensitivity was studied in a series of Huntington's Disease (HD) patients and controls by measurement of radiation-induced chromosome aberrations in lymphocytes and by clonogenic survival of lymphoblastoid cell lines. As a group, HD patients were found to be significantly more radiosensitive than controls (p less than 0.001), but there was an overlap between values for the two groups such that an absolute distinction is not possible. These data are consistent with an association between HD and radiosensitivity but not with identity between HD and a radiosensitive phenotype, so that cellular radiosensitivity cannot be used for individual diagnosis. Analysis of three families including 5 HD patients and 11 first-degree relative confirmed this conclusion and demonstrated that even within a given family presymptomatic diagnosis cannot be based on measurement of radiosensitivity. However, the common association of cellular radiosensitivity with HD probands and their families provides a potential lead to the identification of HD gene(s) and so to an eventual understanding of the aetiopathogenesis of this disease at the molecular level.

Cell Line↗
PubMed1981

Ovalocytosis in Papua New Guinea -- dominantly inherited resistance to malaria.

Analysis of ovalocytosis in families has demonstrated dominant inheritance. This conclusion is based on finding ovalocytic children of ovalocytic Melanesian mothers and normocytic Caucasian fathers. Inheritance of resistance to thermal deformation and to crenation upon storage correlated with inheritance of ovalocytic erythrocyte morphology. The latter was associated with in vitro resistance to invasion by P. falciparum.

Elliptocytosis, Hereditary↗
PubMed1980

Mammalian cell function mediating recombination of genetic elements.

Recombination of segments of the SV40 genome by a variety of mechanisms is described. These include the faithful joining of linear segments that have flush termini as opposed to previously described cohesive or resected termini. Lack of involvement of viral proteins has been demonstrated for recombination of segments with homologous overlapping termini, but probably applies also to the other joining reactions. Segments of the genome that have been cleaved in such a manner as to be unable to manufacture any known viral proteins are neutral elements of genetic information, incapable of selection by replication or biological function until recombined. These recombination functions presumably are available to the host cell and any element of genetic information that can be generated in that cell.

Animals↗
PubMed1980

Analysis of recombination in mammalian cells using SV40 genome segments having homologous overlapping termini.

Segments of SV40 DNA having homologous overlapping termini recombine to produce viable genomes in monkey cells. Frequencies of recombination on either side of a deletion marker are non-random; replication and palindromes do not appear to be essential. Since recombination involves host enzymes, a suitable system has been devised for analysing host cell recombination functions.

Animals↗