Supercharging rice photosynthesis to increase yield.
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Breeding↗
Biomedical subjects
P L Mitchell
Publications and source records attributed to P L Mitchell.
Bi-phasic growth patterns in rice.
BACKGROUND AND AIMS: When examining the growth patterns of rice crops for a 5-year period, it was found that the time course of accumulation of above-ground dry matter did not follow a simple sigmoid curve as expected for a monocarpic plant. Instead, there was a decrease in growth around flowering, followed by an increase and then a final decrease of growth at crop maturity. There are two nearly equal phases of growth in rice, with about half of the first phase of vegetative growth preceding reproductive growth. METHODS: Logistic curves were fitted separately to the vegetative parts of the crop and to the reproductive parts (the panicle). When the curves were summed, the combined curve gave a good description of the time course of above-ground dry matter, capturing the pause in growth and its resumption. The overall pattern of growth can be seen to be the result of this bi-phasic nature of the crop. KEY RESULTS: Variations in the panicle phase of growth were shown to be largely a consequence of year-to-year variations in the weather, whereas the vegetative phase seemed largely independent of those variations. CONCLUSIONS: Analysing rice growth as two components, each with a logistic curve, provides insight into the growth processes of the plant and the pattern of yield formation.
Logistic Models↗
Positron emission tomography scanning in the assessment of patients with lymphoma.
BACKGROUND: The detection of lymphoma by computed tomography (CT) scanning is known to be improved by positron emission tomography (PET) and/or gallium scanning, although the direct comparative accuracy of these imaging modalities remains a subject of ongoing review. AIMS: The aim of the present study was to compare PET scanning with conventional imaging (CT and/or gallium scanning) in patients with lymphoma. METHODS: A retrospective study of 38 patients (25 men; 13 women; median age 39.5 years; range 18.0-81.0 years) who had had PET scans (24 scans at initial staging and 46 scans at restaging, including suspected disease relapse) was carried out. Thirty-one concurrent gallium scans had been performed. Disease was validated with clinical follow up or biopsy. RESULTS: The sensitivities of PET and CT at initial staging were 96 and 71%, respectively. PET identified additional sites of disease compared with CT in 29% of patients. Of the 15 patients who had had all three imaging modalities, the sensitivities of PET, CT and gallium were 93, 67 and 87%, respectively. At treatment completion, the positive predictive values of PET, CT and gallium scans for relapse given a residual mass were 100, 33 and 0%, respectively (P = 0.006 for PET and CT comparison). The negative predictive values of PET, CT and gallium were 76, 0 and 70%, respectively (P-value not significant). In suspected disease relapse, PET results changed management in 50% of patients. CONCLUSION: Compared with CT and gallium scans, PET has superior accuracy in staging and restaging, and its greatest value lies in its positive predictive value for relapse in patients with residual masses.
Adolescent↗
Time to chill: effects of simulated global change on leaf ice nucleation temperatures of subarctic vegetation.
We investigated the effects of long-term (7-yr) in situ CO(2) enrichment (600 μmol/mol) and increased exposure to UV-B radiation, the latter an important component of global change at high latitudes, on the ice nucleation temperatures of leaves of several evergreen and deciduous woody ericaceous shrubs in the subarctic (68° N). Three (Vaccinium uliginosum, V. vitis-idaea, and Empetrum hermaphroditum) of the four species of shrubs studied showed significantly higher ice nucleation temperatures throughout the 1999 growing season in response to CO(2) enrichment and increased exposure to UV-B radiation relative to the controls. The same species also showed a strong interactive effect when both treatments were applied together. In all cases, leaves cooled to below their ice nucleation temperatures failed to survive the damage resulting from intracellular ice formation. Our results strongly suggest that future global change on a decadal time scale (atmospheric CO(2) increases and polar stratospheric O(3) destruction) will lead to increased foliage damage of subarctic vegetation by severe late spring or early autumnal frosting events. Indeed, in support of our experimental findings, there is now some evidence that increases in atmospheric CO(2) concentration over the past three to four decades may already have acted in this manner on high-elevation arboreal plants in the Swedish Scandes. The implications for vegetation modeling in a future "greenhouse" world and palaeoclimate estimates from high-latitude plant fossils dating to the high-CO(2) environment of the Mesozoic are discussed.
Journal Article↗
Assessing the potential for the stomatal characters of extant and fossil Ginkgo leaves to signal atmospheric CO2 change.
The stomatal density and index of fossil Ginkgo leaves (Early Jurassic to Early Cretaceous) have been investigated to test whether these plant fossils provide evidence for CO(2)-rich atmosphere in the Mesozoic. We first assessed five sources of natural variation in the stomatal density and index of extant Gingko biloba leaves: (1) timing of leaf maturation, (2) young vs. fully developed leaves, (3) short shoots vs. long shoots, (4) position in the canopy, and (5) male vs. female trees. Our analysis indicated that some significant differences in leaf stomatal density and index were evident arising from these considerations. However, this variability was considerably less than the difference in leaf stomatal density and index between modern and fossil samples, with the stomatal index of four species of Mesozoic Ginkgo (G. coriacea, G. huttoni, G. yimaensis, and G. obrutschewii) 60-40% lower than the modern values recorded in this study for extant G. biloba. Calculated as stomatal ratios (the stomatal index of the fossil leaves relative to the modern value), the values generally tracked the CO(2) variations predicted by a long-term carbon cycle model confirming the utility of this plant group to provide a reasonable measure of ancient atmospheric CO(2) change.
Journal Article↗
Open label, multi-centre phase II study of raltitrexed ('Tomudex') in patients with inoperable squamous-cell carcinoma of head and neck.
BACKGROUND: Raltitrexed ('Tomudex') is a folate based inhibitor of thymidylate synthase which has been registered in Europe and Australia for the treatment of advanced colorectal cancer. In a European phase I trial of raltitrexed anti-tumour activity was seen in two patients with head and neck cancer, prompting the current study. PATIENTS AND METHODS: From November 1996 to December 1998, 24 patients with metastatic or recurrent squamous-cell carcinoma of the head and neck from 7 Australian centres received raltitrexed, 3 mg/m2 given intravenously over 15 minutes every 3 weeks, for a maximum of 6 cycles. Patients were required to be chemotherapy naïve and have measurable disease, age > 18 years, WHO performance status initially < or = 2, no significant intercurrent illness or organ dysfunction and a life expectancy > 12 weeks. RESULTS: Twenty-two men and two women, median age 65 years, median performance status 1 were enrolled. Fifteen patients (63%) had received both prior surgery and radiotherapy. In 15 patients (63%) there was recurrent locoregional disease only. Twelve patients (50%) received one cycle of treatment with only four patients (17%) receiving four or more cycles of treatment. No patient achieved a complete or partial response, although 5 patients experienced stable disease which lasted a median of 188 days (range 61-436). The median survival for the whole group was 101 days (range 20436). Raltitrexed was generally well tolerated with minimal antiproliferative toxicity. CONCLUSIONS: Single-agent raltitrexed does not demonstrate significant anti-tumour response rates in patients with predominantly locally recurrent head and neck cancer.
Adult↗
Quality of life and cisplatin-gemcitabine chemotherapy.
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Antineoplastic Agents↗
Treatment of nondysgerminomatous ovarian germ cell tumors: an analysis of 69 cases.
BACKGROUND: Combination chemotherapy has dramatically improved the prognosis of patients with nondysgerminomatous ovarian germ cell tumors (NDOGCT). However, guidelines are needed for the identification of patients at risk of relapse. METHODS: The authors performed a retrospective analysis of women with NDOGCT managed during the period 1970-1994 at the Royal Marsden Hospital and other hospitals of the London Gynaecological Oncology Group. RESULTS: Sixty-nine women were included; their median follow-up was 5.7 years (minimum, 12 months). The median age was 21 years (range, 4-44 years), with a histology of immature teratoma (IT) for 17 patients, endodermal sinus tumor (EST) for 20 patients, and mixed tumors for 32 patients. Thirty-five patients (51%) had Stage I disease. Nine patients with Stage I tumors were observed without further therapy (six with IT and three with mixed tumors), and one relapsed. Seven patients received non-platinum-based chemotherapy, and four relapsed. A total of 52 patients were treated with platinum-based chemotherapy, with relapse free and overall survival rates of 87% (95% confidence interval [CI], 73-93%) and 84% (95% CI, 70-91%), respectively. Of these patients, relapse was seen in 0 of 9 IT patients, 1 of 25 patients with mixed tumors, and 6 of 18 EST patients. With alpha-fetoprotein (AFP) > 1000 kU/L, relapse was seen in 6 of 18 patients compared with 1 of 33 relapses with lower AFP levels. In multivariate analysis, including all patients who received chemotherapy, AFP >1000 kU/L (P = 0.001) and non-platinum-based chemotherapy (P = 0.005) were associated with relapse. When only patients given platinum-based treatment were considered, EST histology (P = 0.003) and AFP >1000 kU/L (P = 0.003) were associated with relapse in univariate analysis; however, these factors were linked. No malignant tumor was found at second-look surgery performed on 24 patients. Of 26 women assessable for fertility, 24 subsequently recommenced regular menstrual function, and 11 patients had pregnancies. CONCLUSIONS: Platinum-based chemotherapy has been confirmed to be effective in the management of patients with NDOGCT. Relapses were principally seen among patients with AFP >1000 kU/L or pure EST histology. Efforts to improve outcome need to focus on patients with EST, whereas less intensive management strategies may be appropriate for some patients with IT.
Adolescent↗
Granulocyte-macrophage-colony-stimulating factor in established febrile neutropenia.
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Fever↗
Positron emission tomography in assessing response to neoadjuvant chemotherapy for non-small-cell lung cancer.
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Aged↗
Liposomal vincristine for the treatment of human acute lymphoblastic leukaemia in severe combined immunodeficient (SCID) mice.
Non-obese diabetic NOD/SCID mice have been used to grow human leukaemia as a systemic disease. The animals were inoculated with leukaemic cells obtained from a 36-year-old male with early B-cell precursor acute lymphoblastic leukaemia and on day 15 were given the first of three weekly injections of 1 mg/kg vincristine or equimolar liposomal vincristine. The development of leukaemia in the mice was monitored by taking weekly blood samples and measuring the cell content by flow cytometry. The median time to 50% human cells in the peripheral blood of mice treated with free vincristine was 41 d from the start of treatment compared with 49 d for mice treated with liposomal vincristine (P < 0.01). The median day of death for mice treated with free vincristine was 47 d from the start of treatment and 57 d for mice receiving liposomal vincristine (P<0.01), thus providing a 21% increase in lifespan for animals treated with the liposomal preparation. There was slightly greater weight loss in mice treated with free vincristine than those given liposomal vincristine. Measurement of in vitro colony forming bone marrow progenitor cells in similarly treated, tumour-free mice, showed no difference in progenitor cell survival between mice that received either type of vincristine. We conclude that encapsulating vincristine in liposomes improves the therapeutic index of this drug measured in mice bearing human leukaemia. This may lead to use of the drug in conventional combination chemotherapy with greater safety or, in this setting, at higher dosage.
Adult↗
Growth of human T-cell lineage acute leukemia in severe combined immunodeficiency (SCID) mice and non-obese diabetic SCID mice.
Primary leukemic cells from patients with acute lymphoblastic leukemia (ALL) can be injected intravenously into mice with severe combined immunodeficiency (SCID) to create a model of human leukemia. Leukemic cells disseminate to murine tissues in a clinicopathologic pattern similar to that seen in humans. Thus far, reports of engraftment of lymphoid leukemia in SCID mice have mainly been from patients with B-cell lineage ALL, for which engraftment occurs more frequently with cells from high-risk patients. There are few data on the engraftment of T-cell lineage ALL in SCID mice. Leukemic cells from 19 patients (16 adult and three pediatric) with T-cell lineage ALL were injected into SCID mice, with overt engraftment of 12 cases (63%). Engraftment of leukemia in SCID mice was associated with earlier death due to leukemia of the patient donors (P < .01, log-rank test). The recently developed non-obese diabetic (NOD)/SCID mouse may expand the uses of the SCID model. Cells from the seven patients with T-cell lineage ALL that failed to cause leukemia in SCID mice were injected into NOD/SCID mice. Overt leukemia engraftment was observed in all seven cases. Thus, growth of human T-cell lineage ALL cells in SCID mice was associated with a high-risk patient group. However, this association was not observed when NOD/SCID mice were used, suggesting that this model would no longer predict patients likely to die early of leukemia, but may provide a more realistic system for studying the biology and treatment of the disease.
Acute Disease↗
Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.
PURPOSE: Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective. PATIENTS AND METHODS: In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated. RESULTS: Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04). CONCLUSION: Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.
Anti-Bacterial Agents↗
Interleukin-4 enhances the survival of severe combined immunodeficient mice engrafted with human B-cell precursor leukemia.
Human interleukin-4 (huIL-4) has been shown to inhibit the growth in vitro of cells from patients with acute lymphoblastic leukemia (ALL). With the aim of determining whether this cytokine might be useful in the treatment of patients with ALL, the effects of huIL-4 on human B-cell precursor ALL engrafted in severe combined immunodeficient (SCID) mice were examined. The inhibition of [3H] thymidine uptake of primary ALL cells by huIL-4 was maintained following engraftment and passage of leukemia in SCID mice. Five of seven xenograft leukemias showed significant inhibition in vitro by huIL-4 at concentrations as low as 0.5 ng/mL; furthermore, huIL-4 counteracted the proliferative effects of IL-7. When used to treat two human leukemias engrafted in SCID mice, huIL-4 200 microgram/kg/d, as a continuous 14-day subcutaneous infusion, suppressed the appearance of circulating lymphoblasts and extended survival of mice by 39% and 108%, respectively, the first demonstration of IL-4 activity against human leukemia in vivo. The mean steady-state huIL-4 level in mouse plasma during the infusion was 1.46 ng/mL (SEM +/- 0.14 ng/mL), which was similar to concentrations found to be effective in vitro. ALL cells obtained from mice relapsing after huIL-4 treatment continued to show inhibition by the cytokine in vitro. These data suggest that IL-4 may be useful in the treatment of patients with ALL.
Animals↗
Phase II trial of procarbazine, vincristine and lomustine (POC) chemotherapy in metastatic cutaneous malignant melanoma.
40 patients with symptomatic metastatic melanoma were treated with procarbazine, vincristine and lomustine (POC). 4 patients had received chemotherapy previously. Responses were seen in 8 patients (20%), 4 of whom had a complete remission. All responding patients had some tumour shrinkage after one cycle. The median duration of response was 27 weeks, with 2 patients remaining in complete remission at 6 and 6.5 years. The median survival for the whole group was 22 weeks, whilst that of the responding patients was 35 weeks. Using conventional anti-emetics, the principal toxicities were nausea and vomiting, severe in 15% of cycles. Other nonhaematological toxicity was uncommon. Neutropenia (WHO grade 3 or 4) occurred in 11% of cycles and thrombocytopenia in 8%. The response rate of metastatic melanoma to POC chemotherapy was similar to other cytotoxic regimens though toxicity, other than nausea and vomiting, was minimal. The rapid response allows patients with unresponsive disease to be identified early, avoiding continuing toxicity.
Adult↗
Peripheral blood stem cells used to augment autologous bone marrow transplantation.
Peripheral blood stem cells (PBSC) were used to augment autologous bone marrow transplantation (ABMT), aiming to hasten engraftment after high dose treatment in a group of heavily pretreated patients. PBSC were obtained by leukapheresis during the rebound after standard chemotherapy. In 11 patients aged 7-17 years, high dose chemotherapy consisted of busulphan 16 mg/kg orally with melphalan 160 mg/m2 intravenously for seven patients, and melphalan 200 mg/m2 intravenously alone for four. The median number of granulocyte-macrophage colony forming units in the reinfused PBSC was 3.42 x 10(4)/kg (3.03-18.01) and bone marrow 12.4 x 10(4)/kg (4.16-28.6). Neutrophil recovery to > or = 0.5 x 10(9)/l and platelet transfusion independence occurred at a median of 14 days (11-18) and 22 days (9-84) respectively. In five patients the early engraftment was transient with neutrophils again dropping below 0.5 x 10(9)/l then slowly recovering. There was one toxic death due to sepsis. PBSC harvesting in these children was undertaken without interrupting routine chemotherapy and without the use of bone marrow growth factors. In some patients PBSC failed to influence engraftment and the use of combined chemotherapy and growth factor priming for PBSC collection may give improved results.
Acute Disease↗
Palliation of biliary obstruction in patients with advanced breast cancer using endoscopic stents.
Endoscopic insertion of a biliary endoprosthesis was successful in eight patients with extrahepatic biliary obstruction caused by breast cancer metastases. The serum bilirubin level was significantly reduced in seven patients and in four this was accompanied by marked symptomatic improvement. Endoprostheses required replacement after a median of 8 (range 3-127) weeks. Two patients responding to systemic anticancer therapy survived 27 and 43 months. Endoscopically placed stents offer effective palliation of extrahepatic biliary obstruction caused by metastatic breast cancer and long-term survival may be possible.
Adult↗
Ondansetron reduces chemotherapy induced nausea and vomiting refractory to standard antiemetics.
Ondansetron, a selective 5HT3 (serotonin) antagonist, was used in patients refractory to standard antiemetics. Seventy-five patients receiving chemotherapy without cisplatin were given ondansetron 4 mg IV and 4 mg orally immediately prior to chemotherapy, then 8 mg orally after six and 12 hours, followed by 8 mg orally eight hourly during days 2-5. Complete control of vomiting occurred in 52 patients (69%) on the first day and 45 patients (60%) on days 2-5. Sixty patients (80%) preferred ondansetron to their previous antiemetics. The efficacy of ondansetron was maintained over multiple chemotherapy cycles. Ondansetron was also given to 16 patients receiving cisplatin chemotherapy. They received 8 mg IV immediately prior to chemotherapy followed by an infusion of 1 mg/hr for 8 hr, with 8 mg orally at the end of the infusion and then 8 mg orally eight hourly during days 2-6. Some control of vomiting (less than = 5 vomits) was achieved in eight patients (50%) on the first day and in 14 patients (87%) on subsequent days. Eight patients (50%) preferred ondansetron to their previous antiemetics. Adverse events with ondansetron were frequent but mild, with constipation and headache being most common. Ondansetron is highly effective in patients refractory to standard antiemetics, especially after noncisplatin chemotherapy.
Adult↗