Ethanol concentration and chlorophyll fluorescence were measured as signs of heat stress in apple... more Ethanol concentration and chlorophyll fluorescence were measured as signs of heat stress in apple fruit [Malus sylvestris (L.) Mill. var. domestica (Borkh.) Mansf.]. 'Mclntosh', 'Cortland', 'Jonagold', and 'Northern Spy' apples were held at 46°C for 0, 4, 8, or 12 h. Following treatments, fruit were stored at 0°C in air and evaluated after 0, 4, 8, or 12 weeks. Peel and flesh browning, headspace ethanol concentration, and chlorophyll fluorescence (Fv/Fm) were measured. Peel browning became apparent in all 4 cultivars 4 weeks after treatment and increased during storage. Exposure to 46°C for 12 h caused severe flesh browning in all cultivars. Severity of flesh browning increased with increasing heat treatment time and storage time. Headspace ethanol concentrations immediately following 12 h heat treatments increased and were 48-, 70-, 9-, and 170- fold higher in 'Mclntosh', 'Cortland', 'Jonagold', and 'Northern Spy' apples than in the controls, respectively. Ethanol concentrations also increased in fruit treated for 8 h but not in those treated for 4 h. Ethanol concentrations were maintained or increased during the 12 weeks of storage. Heat treatments reduced chlorophyll fluorescence (Fv/Fm). One day following treatment, fruit exposed to 46°C for 12 h had Fv/Fm values that were 36%, 59%, 63%, and 36% of the control values in 'Mclntosh', 'Cortland', 'Jonagold', and 'Northern Spy', respectively. The 8 h heat treatment also decreased Fv/Fm in treated fruit, but the 4 h treatment had no effect. Fv/Fm decreased in all treatments during storage. Correlations between flesh browning and ethanol concentration ranged from 0.87 to 0.78, and flesh browning and Fv/Fm ranged from -0.91 to -0.67 depending on cultivar. The increase in ethanol production and decrease in chlorophyll fluorescence were apparent before browning was visually apparent and have the potential to predict injury that develops during storage.
Microtubule-stabilizing agents (MTSAs), including the taxanes and epothilones, are effective chem... more Microtubule-stabilizing agents (MTSAs), including the taxanes and epothilones, are effective chemotherapeutic agents for the treatment of many cancers. Neuropathy is a major adverse effect of MTSA-based chemotherapy, with severe peripheral neuropathy (grade 3 or 4) occurring in as many as 30% of patients treated with a MTSA. MTSA-induced neuropathy usually resolves gradually after cessation of the treatment. The most reliable method to accurately assess MTSA-induced neuropathy is by clinical evaluation, although additional techniques are being developed and evaluated. Among MTSA-induced neuropathy, the most extensively studied is that induced by taxanes; such a neuropathy usually presents as sensory neuropathy and is more common with paclitaxel than docetaxel. The incidence of MTSA-induced neuropathy seems to depend on the MTSA dose per treatment cycle, the schedule of treatment, and the duration of the infusion. Although there have been several small clinical trials with neuroprote...
Peripheral neuropathy is a serious, dose-limiting side effect of cancer treatment with microtubul... more Peripheral neuropathy is a serious, dose-limiting side effect of cancer treatment with microtubule-targeting drugs. Symptoms present in a "stocking-glove" distribution, with longest nerves affected most acutely, suggesting a length-dependent component to the toxicity. Axonal transport of ATP-producing mitochondria along neuronal microtubules from cell body to synapse is crucial to neuronal function. We compared the effects of the drugs paclitaxel and ixapebilone that bind along the lengths of microtubules and the drugs eribulin and vincristine that bind at microtubule ends, on mitochondrial trafficking in cultured human neuronal SK-N-SH cells and on axonal transport in mouse sciatic nerves. Antiproliferative concentrations of paclitaxel and ixabepilone significantly inhibited the anterograde transport velocity of mitochondria in neuronal cells, whereas eribulin and vincristine inhibited transport only at significantly higher concentrations. Confirming these observations, a...
Vinepidine, a new derivative of vincristine, and three clinically used Catharanthus derivatives, ... more Vinepidine, a new derivative of vincristine, and three clinically used Catharanthus derivatives, vinblastine, vincristine, and vindesine, were examined for their abilities to inhibit net tubulin addition at the assembly ends of bovine brain microtubules at steady state. Although all four derivatives were generally similar in potency, their relative abilities to inhibit tubulin addition were distinguishable. Vinepidine and vincristine were the most potent derivatives (Ki, 0.079 +/- 0.018 (SD) microM and 0.085 +/- 0.013 microM, respectively), followed by vindesine (Ki, 0.110 +/- 0.007 microM) and vinblastine (Ki, 0.178 +/- 0.025 microM). In contrast to their relative abilities to inhibit microtubule assembly in vitro, vinblastine and its derivative, vindesine, were generally more potent than vincristine and vinepidine in inhibiting cell proliferation in culture. Vinblastine was nine times more potent than the weakest derivative, vinepidine, in B16 melanoma cells. In L-cells, vinblasti...
We have used a structure-activity approach to investigate whether the Vinca alkaloids inhibit cel... more We have used a structure-activity approach to investigate whether the Vinca alkaloids inhibit cell proliferation primarily by means of their effects on mitotic spindle microtubules or by another mechanism or by a combination of mechanisms. Five Vinca alkaloids were used to investigate the relationship in HeLa cells between inhibition of cell proliferation and blockage of mitosis, alteration of spindle organization, and depolymerization of microtubules. Indirect immunofluorescence staining of microtubules and 4,6-diamidino-2-phenylindole staining of chromatin were used to characterize the effects of the drugs on the distributions of cells in stages of the cell cycle and on the organization of microtubules and chromosomes in metaphase spindles. The microtubule polymer was isolated from cells and quantified using a competitive enzyme-linked immunoadsorbent assay for tubulin. We observed a nearly perfect coincidence between the concentration of each Vinca derivative that inhibited cell ...
The length dynamics both of microtubule-associated protein (MAP)-rich and MAP-depleted bovine bra... more The length dynamics both of microtubule-associated protein (MAP)-rich and MAP-depleted bovine brain microtubules were examined at polymer mass steady state. In both preparations, the microtubules exhibited length redistributions shortly after polymer mass steady state was attained. With time, however, both populations relaxed to a state in which no further changes in length distributions could be detected. Shearing the microtubules or diluting the microtubule suspensions transiently increased the extent to which microtubule length redistributions occurred, but again the microtubules relaxed to a state in which changes in the polymer length distributions were not detected. Under steady-state conditions of constant polymer mass and stable microtubule length distribution, both MAP-rich and MAP-depleted microtubules exhibited behavior consistent with treadmilling. MAPs strongly suppressed the magnitude of length redistributions and the steady-state treadmilling rates. These data indicat...
The neural microtubule-associated protein tau binds to and stabilizes microtubules. Because of al... more The neural microtubule-associated protein tau binds to and stabilizes microtubules. Because of alternative mRNA splicing, tau is expressed with either 3 or 4 C-terminal repeats. Two observations indicate that differences between these tau isoforms are functionally important. First, the pattern of tau isoform expression is tightly regulated during development. Second, mutation-induced changes in tau RNA splicing cause neuronal cell death and dementia simply by altering the isoform expression ratio. To investigate whether 3- and 4-repeat tau differentially regulate microtubule behavior in cells, we microinjected physiological levels of these two isoforms into EGFP-tubulin–expressing cultured MCF7 cells and measured the effects on the dynamic instability behavior of individual microtubules by time-lapse microscopy. Both isoforms suppressed microtubule dynamics, though to different extents. Specifically, 4-repeat tau reduced the rate and extent of both growing and shortening events. In ...
Ethanol concentration and chlorophyll fluorescence were measured as signs of heat stress in apple... more Ethanol concentration and chlorophyll fluorescence were measured as signs of heat stress in apple fruit [Malus sylvestris (L.) Mill. var. domestica (Borkh.) Mansf.]. 'Mclntosh', 'Cortland', 'Jonagold', and 'Northern Spy' apples were held at 46°C for 0, 4, 8, or 12 h. Following treatments, fruit were stored at 0°C in air and evaluated after 0, 4, 8, or 12 weeks. Peel and flesh browning, headspace ethanol concentration, and chlorophyll fluorescence (Fv/Fm) were measured. Peel browning became apparent in all 4 cultivars 4 weeks after treatment and increased during storage. Exposure to 46°C for 12 h caused severe flesh browning in all cultivars. Severity of flesh browning increased with increasing heat treatment time and storage time. Headspace ethanol concentrations immediately following 12 h heat treatments increased and were 48-, 70-, 9-, and 170- fold higher in 'Mclntosh', 'Cortland', 'Jonagold', and 'Northern Spy' apples than in the controls, respectively. Ethanol concentrations also increased in fruit treated for 8 h but not in those treated for 4 h. Ethanol concentrations were maintained or increased during the 12 weeks of storage. Heat treatments reduced chlorophyll fluorescence (Fv/Fm). One day following treatment, fruit exposed to 46°C for 12 h had Fv/Fm values that were 36%, 59%, 63%, and 36% of the control values in 'Mclntosh', 'Cortland', 'Jonagold', and 'Northern Spy', respectively. The 8 h heat treatment also decreased Fv/Fm in treated fruit, but the 4 h treatment had no effect. Fv/Fm decreased in all treatments during storage. Correlations between flesh browning and ethanol concentration ranged from 0.87 to 0.78, and flesh browning and Fv/Fm ranged from -0.91 to -0.67 depending on cultivar. The increase in ethanol production and decrease in chlorophyll fluorescence were apparent before browning was visually apparent and have the potential to predict injury that develops during storage.
Microtubule-stabilizing agents (MTSAs), including the taxanes and epothilones, are effective chem... more Microtubule-stabilizing agents (MTSAs), including the taxanes and epothilones, are effective chemotherapeutic agents for the treatment of many cancers. Neuropathy is a major adverse effect of MTSA-based chemotherapy, with severe peripheral neuropathy (grade 3 or 4) occurring in as many as 30% of patients treated with a MTSA. MTSA-induced neuropathy usually resolves gradually after cessation of the treatment. The most reliable method to accurately assess MTSA-induced neuropathy is by clinical evaluation, although additional techniques are being developed and evaluated. Among MTSA-induced neuropathy, the most extensively studied is that induced by taxanes; such a neuropathy usually presents as sensory neuropathy and is more common with paclitaxel than docetaxel. The incidence of MTSA-induced neuropathy seems to depend on the MTSA dose per treatment cycle, the schedule of treatment, and the duration of the infusion. Although there have been several small clinical trials with neuroprote...
Peripheral neuropathy is a serious, dose-limiting side effect of cancer treatment with microtubul... more Peripheral neuropathy is a serious, dose-limiting side effect of cancer treatment with microtubule-targeting drugs. Symptoms present in a "stocking-glove" distribution, with longest nerves affected most acutely, suggesting a length-dependent component to the toxicity. Axonal transport of ATP-producing mitochondria along neuronal microtubules from cell body to synapse is crucial to neuronal function. We compared the effects of the drugs paclitaxel and ixapebilone that bind along the lengths of microtubules and the drugs eribulin and vincristine that bind at microtubule ends, on mitochondrial trafficking in cultured human neuronal SK-N-SH cells and on axonal transport in mouse sciatic nerves. Antiproliferative concentrations of paclitaxel and ixabepilone significantly inhibited the anterograde transport velocity of mitochondria in neuronal cells, whereas eribulin and vincristine inhibited transport only at significantly higher concentrations. Confirming these observations, a...
Vinepidine, a new derivative of vincristine, and three clinically used Catharanthus derivatives, ... more Vinepidine, a new derivative of vincristine, and three clinically used Catharanthus derivatives, vinblastine, vincristine, and vindesine, were examined for their abilities to inhibit net tubulin addition at the assembly ends of bovine brain microtubules at steady state. Although all four derivatives were generally similar in potency, their relative abilities to inhibit tubulin addition were distinguishable. Vinepidine and vincristine were the most potent derivatives (Ki, 0.079 +/- 0.018 (SD) microM and 0.085 +/- 0.013 microM, respectively), followed by vindesine (Ki, 0.110 +/- 0.007 microM) and vinblastine (Ki, 0.178 +/- 0.025 microM). In contrast to their relative abilities to inhibit microtubule assembly in vitro, vinblastine and its derivative, vindesine, were generally more potent than vincristine and vinepidine in inhibiting cell proliferation in culture. Vinblastine was nine times more potent than the weakest derivative, vinepidine, in B16 melanoma cells. In L-cells, vinblasti...
We have used a structure-activity approach to investigate whether the Vinca alkaloids inhibit cel... more We have used a structure-activity approach to investigate whether the Vinca alkaloids inhibit cell proliferation primarily by means of their effects on mitotic spindle microtubules or by another mechanism or by a combination of mechanisms. Five Vinca alkaloids were used to investigate the relationship in HeLa cells between inhibition of cell proliferation and blockage of mitosis, alteration of spindle organization, and depolymerization of microtubules. Indirect immunofluorescence staining of microtubules and 4,6-diamidino-2-phenylindole staining of chromatin were used to characterize the effects of the drugs on the distributions of cells in stages of the cell cycle and on the organization of microtubules and chromosomes in metaphase spindles. The microtubule polymer was isolated from cells and quantified using a competitive enzyme-linked immunoadsorbent assay for tubulin. We observed a nearly perfect coincidence between the concentration of each Vinca derivative that inhibited cell ...
The length dynamics both of microtubule-associated protein (MAP)-rich and MAP-depleted bovine bra... more The length dynamics both of microtubule-associated protein (MAP)-rich and MAP-depleted bovine brain microtubules were examined at polymer mass steady state. In both preparations, the microtubules exhibited length redistributions shortly after polymer mass steady state was attained. With time, however, both populations relaxed to a state in which no further changes in length distributions could be detected. Shearing the microtubules or diluting the microtubule suspensions transiently increased the extent to which microtubule length redistributions occurred, but again the microtubules relaxed to a state in which changes in the polymer length distributions were not detected. Under steady-state conditions of constant polymer mass and stable microtubule length distribution, both MAP-rich and MAP-depleted microtubules exhibited behavior consistent with treadmilling. MAPs strongly suppressed the magnitude of length redistributions and the steady-state treadmilling rates. These data indicat...
The neural microtubule-associated protein tau binds to and stabilizes microtubules. Because of al... more The neural microtubule-associated protein tau binds to and stabilizes microtubules. Because of alternative mRNA splicing, tau is expressed with either 3 or 4 C-terminal repeats. Two observations indicate that differences between these tau isoforms are functionally important. First, the pattern of tau isoform expression is tightly regulated during development. Second, mutation-induced changes in tau RNA splicing cause neuronal cell death and dementia simply by altering the isoform expression ratio. To investigate whether 3- and 4-repeat tau differentially regulate microtubule behavior in cells, we microinjected physiological levels of these two isoforms into EGFP-tubulin–expressing cultured MCF7 cells and measured the effects on the dynamic instability behavior of individual microtubules by time-lapse microscopy. Both isoforms suppressed microtubule dynamics, though to different extents. Specifically, 4-repeat tau reduced the rate and extent of both growing and shortening events. In ...
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Papers by Mary Jordan