Administrative and health policy training for residents.
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Curriculum↗
Biomedical subjects
J Plumb
Publications and source records attributed to J Plumb.
Differential intracellular processing of the anthracycline drug ME2303 in doxorubicin-sensitive (A2780) and -resistant (A2780AD) human ovarian cancer cells as studied with confocal laser scanning microscopy and image analysis.
Laser scanning confocal microscopy has been used to follow the uptake and efflux of the 2-fluoroglycoside of doxorubicin, ME2303, in live cultures of the human ovarian cancer cell line A2780 and its doxorubicin-resistant variant A2780AD. Our methods combine confocal laser scanning microscopy and image analysis to examine the dynamics of anthracycline drugs in cancer cells. Cytotoxicity determined by MTT dye reduction showed that A2780AD cells were more than 400 times less sensitive to doxorubicin compared to A2780 cells but almost 9 times more sensitive to ME2303 compared to doxorubicin. The naturally fluorescent drug was tracked within live cells at 37 degrees C to provide time-course information in relation to nuclear and Golgi-associated cellular domains, as indicated by BODIPY FL ceramide-associated fluorescence. In both cell types, ME2303 was characterised by strong nuclear membrane and perinucleolar fluorescence and as a localised punctate pattern within the nucleus. A2780AD cells accumulated ME2303 in their nuclei at a much reduced rate compared to the doxorubicin-sensitive cells, and ME2303 efflux from resistant cell nuclei was approximately twice as fast as from A2780 cells. The relative uptake of ME2303 into Golgi-associated domains and the nucleus were monitored simultaneously during the initial 35 min of exposure to 10 microM ME2303 and during the first 45 min of a "chase" culture following exposure to 20 microM ME2303. ME2303 was detectable within the Golgi-associated domains of A2780 cells several minutes later and in less relative concentration than in A2780AD cells 15 min into a chase culture. Our results suggest the direct involvement of differences in drug processing via the Golgi apparatus in the expression of P-glycoprotein-related drug resistance.
Coloring Agents↗
Characterisation and properties of a small cell lung cancer cell line and xenograft WX322 with marked sensitivity to alpha-interferon.
Controversy exists as to whether interferons usefully influence the growth of epithelial carcinomas. A small cell lung carcinoma (SCLC) cell line, WX322, has been derived which is greater than 1000-fold more sensitive to alpha-interferon (IFN) when grown in agar than other reported SCLC cell lines. The WX322 line has been characterised to prove its epithelial origin and its chemosensitivity compared with that of the NCI-H69 small cell line. The WX322 cell line expresses neuroendocrine and epithelial markers and possesses a morphology consistent with SCLC origin. A concentration of 5 IU ml-1 of IFN produced 50% inhibition of colony formation in agar in the WX322 line, whereas a concentration of greater than 10(5) IU ml-1 was required to produce a comparable effect with the NCI-H69 cell line. In contrast, WX322, possessed similar sensitivity to NCI-H69 cells when exposed to a range of cytotoxic agents. Analysis of the cell cycle indicated that IFN increased the percentage of cells in the G0/G1 phase for the WX322 cell line but increased the percentage in S phase for the NCI-H69 line. Growth of the xenograft, from which the cell line was derived, was also inhibited by IFN at doses greater than 10(5) IU/mouse/day. The WX322 cell line whether grown in agar or as a xenograft shows an unusually high sensitivity to IFN and provides an interesting model for studying mechanisms of IFN cytotoxicity to epithelial cells.
Animals↗
Primary hyperoxaluria (L-glyceric aciduria) in the cat: a newly recognised inherited disease.
The clinical features of a newly recognised inherited disease, primary hyperoxaluria in the cat, are reported. Affected cats developed acute renal failure between five and nine months old owing to the deposition of oxalate crystals in the tubules of the kidney. In addition to the signs attributable to kidney failure the affected animals became profoundly weak; there was evidence of denervation atrophy in skeletal muscle, and accumulations of neurofilaments were found in the proximal axons of the ventral horn cells and dorsal root ganglion cells of the spinal cord. Examination of urine from affected cats revealed L-glyceric aciduria and intermittent hyperoxaluria suggesting that the disease is a feline analogue of the human disorder, primary hyperoxaluria type 2. This supposition was confirmed by liver enzyme studies.
Acute Kidney Injury↗
The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration.
Bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration were measured in rabbits recovering from thrombocytopenia caused by a single injection of anti-platelet serum. Similar measurements were made on rabbits in a steady state of normal platelet production. The effects of a sustained state of thrombocytopenia on megakaryocyte DNA concentration were investigated by repeated daily injections of anti-platelet serum. It is shown that bleeding time depends on both platelet count and mean platelet volume. Furthermore changes in mean platelet volume appear to play a more important role in haemostasis than changes in platelet count. The mean megakaryocyte nuclear DNA concentration is significantly increased after 24 hours of thrombocytopenia and continues to increase as thrombocytopenia is sustained. Thromboxane B2 production/unit volume of platelet is increased in platelets produced after 24 hours of thrombocytopenia compared with platelets produced in normal steady state function. As a consequence platelets produced in response to thrombocytopenia not only have a larger mean platelet volume but are also more reactive. Mean platelet volume, as well as platelet count, should be considered as an index of haemostasis and its dysfunction, thrombosis.
Animals↗
Changes in volume and density of platelets in myocardial infarction.
The distributions of platelet volume and density were measured in 15 men suffering myocardial infarction and in 22 healthy controls. The method used separated 93% of the total platelet population from whole blood. Mean platelet volume of the study group compared with that of controls was increased by a mean of 0.98 fl (p less than 0.001) in the first 12 hours after myocardial infarction, and by 1.24 fl six weeks later (p less than 0.001). Distribution of platelet volume remained log normal after myocardial infarction. Modal platelet density was increased by a mean of 25 g/l (p less than 0.05) after myocardial infarction. Platelet volume is probably chronically large in men suffering myocardial infarction and may be related to changes in megakaryocytes. It is suggested that the increase in platelet volume occurs before infarction.
Adult↗
Sedatives and driving.
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Accidents, Traffic↗