First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients.
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Analysis of Variance↗
Biomedical subjects
J M Stone
Publications and source records attributed to J M Stone.
Psychopathological consequences of ketamine.
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Adult↗
Optimal scheduling to reduce morbidity of involved field radiotherapy with transplantation for lymphomas: a prospective Australasian Leukaemia and Lymphoma Group Study.
This study evaluated delivery of involved field radiotherapy (IFRT) with transplantation for lymphomas timed to minimise toxicity. Patients transplanted for lymphoma had infradiaphragmatic disease irradiated pre-transplant and supradiaphragmatic disease post transplant. A total of 31 patients were studied, with a median follow-up duration of 4 years. Transplant conditioning was according to clinician preference. In all, 14 patients had pre-transplant abdominopelvic IFRT and 19 had post transplant IFRT (including three who had pre-transplant IFRT). Grade III-IV haematological toxicity from pre-transplant IFRT occurred in three patients and from post transplant IFRT in 10 patients. Pre-transplant IFRT had no effect on haematological recovery post transplant, but was associated with a trend towards increased gastrointestinal toxicity (P = 0.094). Pneumonitis due to post transplant thoracic IFRT occurred in one patient. Two patients failed in involved sites after completion of protocol radiotherapy. One case of myelodysplasia has been reported. As sequenced in this study, IFRT was feasible and produced a low incidence of severe pulmonary and haematological toxicities. Patient selection, field size and radiotherapy dose warrant further study.
Adolescent↗
HAESA, an Arabidopsis leucine-rich repeat receptor kinase, controls floral organ abscission.
Abcission, the natural shedding of leaves, flowers and fruits, is a fundamental component of plant development. Abscission is a highly regulated process that occurs at distinct zones of cells that undergo enlargement and subsequent separation. Although some components of abscission, including accumulation of the hormone ethylene and cell wall-degrading enzymes, have been described, the regulatory pathways remain largely unknown. In this paper we describe a critical component required for floral organ abscission in Arabidopsis thaliana, the receptor-like protein kinase HAESA. Histochemical analysis of transgenic plants harboring a HAESA promoter:: beta-glucuronidase reporter gene and in situ RNA hybridization experiments show HAESA expression in the abscission zones where the sepals, petals, and stamens attach to the receptacle, at the base of pedicels, and at the base of petioles where leaves attach to the stem. Immunodetection, immunoprecipitation, and protein kinase activity assays reveal HAESA is a plasma membrane serine/threonine protein kinase. The reduction of function of HAESA in transgenic plants harboring an antisense construct results in delayed abscission of floral organs, and the severity of the phenotype is directly correlated with the level of HAESA protein. These results demonstrate that HAESA functions in developmentally regulated floral organ abscission.
Arabidopsis↗
Simulation of fungal-mediated cell death by fumonisin B1 and selection of fumonisin B1-resistant (fbr) Arabidopsis mutants.
Fumonisin B1 (FB1), a programmed cell death-eliciting toxin produced by the necrotrophic fungal plant pathogen Fusarium moniliforme, was used to simulate pathogen infection in Arabidopsis. Plants infiltrated with 10 microM FB1 and seedlings transferred to agar media containing 1 microM FB1 develop lesions reminiscent of the hypersensitive response, including generation of reactive oxygen intermediates, deposition of phenolic compounds and callose, accumulation of phytoalexin, and expression of pathogenesis-related (PR) genes. Arabidopsis FB1-resistant (fbr) mutants were selected directly by sowing seeds on agar containing 1 microM FB1, on which wild-type seedlings fail to develop. Two mutants chosen for further analyses, fbr1 and fbr2, had altered PR gene expression in response to FB1. fbr1 and fbr2 do not exhibit differential resistance to the avirulent bacterial pathogen Pseudomonas syringae pv maculicola (ES4326) expressing the avirulence gene avrRpt2 but do display enhanced resistance to a virulent isogenic strain that lacks the avirulence gene. Our results demonstrate the utility of FB1 for high-throughput isolation of Arabidopsis defense-related mutants and suggest that pathogen-elicited programmed cell death of host cells may be an important feature of compatible plant-pathogen interactions.
Arabidopsis↗
Fumonisin B1-induced cell death in arabidopsis protoplasts requires jasmonate-, ethylene-, and salicylate-dependent signaling pathways.
We have established an Arabidopsis protoplast model system to study plant cell death signaling. The fungal toxin fumonisin B1 (FB1) induces apoptosis-like programmed cell death (PCD) in wild-type protoplasts. FB1, however, only marginally affects the viability of protoplasts isolated from transgenic NahG plants, in which salicylic acid (SA) is metabolically degraded; from pad4-1 mutant plants, in which an SA amplification mechanism is thought to be impaired; or from jar1-1 or etr1-1 mutant plants, which are insensitive to jasmonate (JA) or ethylene (ET), respectively. FB1 susceptibility of wild-type protoplasts decreases in the dark, as does the cellular content of phenylalanine ammonia-lyase, a light-inducible enzyme involved in SA biosynthesis. Interestingly, however, FB1-induced PCD does not require the SA signal transmitter NPR1, given that npr1-1 protoplasts display wild-type FB1 susceptibility. Arabidopsis cpr1-1, cpr6-1, and acd2-2 protoplasts, in which the SA signaling pathway is constitutively activated, exhibit increased susceptibility to FB1. The cpr6-1 and acd2-2 mutants also constitutively express the JA and ET signaling pathways, but only the acd2-2 protoplasts undergo PCD in the absence of FB1. These results demonstrate that FB1 killing of Arabidopsis is light dependent and requires SA-, JA-, and ET-mediated signaling pathways as well as one or more unidentified factors activated by FB1 and the acd2-2 mutation.
Arabidopsis↗
Behavioral choice treatment promotes continuing weight loss: preliminary results of a cognitive-behavioral decision-based treatment for obesity.
Twenty-four obese women were randomly assigned to 1 of 2 group treatments: behavioral choice treatment (BCT) or traditional behavioral treatment (TBT). BCT uses decision theory to promote moderate behavior change that can be comfortably, and therefore permanently, maintained. Groups completed a moderate-intensity walking program and obtained feedback from computerized eating dairies. The TBT group evidenced greater weight loss at posttreatment. However, the TBT group also evidenced a trend to regain weight, whereas the BCT group continued a slow weight loss during follow-up. Exercise followed a similar pattern. Both groups decreased in restraint and increased in self-esteem.
Adolescent↗
Spatial variations in natural background radiation: absorbed dose rates in air in Colorado.
Large and small-scale spatial variations in natural ambient background radiation dose rates in Colorado were investigated at 1,150 specific locations with particular attention to 40 of the more populated areas along the Front Range of the Rocky Mountains. Total dose rates (including cosmic and terrestrial components) in Front Range communities below 2,000 m elevation averaged 135 nGy h(-1). Terrestrial dose rates had a coefficient of variation of 17%. Communities above 2,000 m had a mean total dose rate of 196 nGy h(-1), and a terrestrial dose rate coefficient of variation of 17%. Across all Front Range communities, the coefficient of variation for terrestrial dose rates was 22%. Within individual communities, coefficient of variation values for terrestrial dose rates ranged from 3 to 21%. Smaller-scale spatial variability (to within a few meters) was relatively small (coefficient of variation values generally ranged from 3 to 7%). A significant linear relationship (r2 = 0.83) between the size of area surveyed (km2) and coefficient of variation value for terrestrial dose rates was found. West of the Continental Divide, the terrestrial component accounted for roughly 60% of total measured dose rates, while east of the Continental Divide, where enriched granitic source rocks and associated soils are prevalent, the terrestrial component generally accounted for two-thirds or more of total dose rates.
Air Pollutants, Radioactive↗
Physicians unions are becoming a viable option.
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Collective Bargaining↗
Interaction of the maize and Arabidopsis kinase interaction domains with a subset of receptor-like protein kinases: implications for transmembrane signaling in plants.
The kinase interaction (KI) domain of kinase-associated protein phosphatase (KAPP) interacts with the phosphorylated form of an Arabidopsis thaliana receptor-like protein kinase (RLK). The KI domain may recruit KAPP into an RLK-initiated signaling complex. To examine additional roles that this domain may play in plant signal transduction, a search was conducted for other KI domain-containing proteins. One gene was isolated which encodes a KI domain, the maize homolog of KAPP. To test whether the maize KI domain associates with other maize proteins, it was used as a probe in a protein-protein interaction cloning strategy. A new maize RLK, KI domain interacting kinase 1 (KIK1), was identified by its interaction with the maize KI domain. The maize KI domain and the KIK1 kinase domain association required phosphorylation of the kinase. This work establishes that the KI domain phosphorylation-dependent signaling mechanism is present in both monocots and dicots. Additionally, it was determined that both the maize and Arabidopsis KI domains interact with several but not all of the active RLKs assayed. These multiple associations imply that KAPP may function in a number of RLK-initiated signaling pathways.
Amino Acid Sequence↗
Plant protein kinase families and signal transduction.
Enzymes of the eukaryotic protein kinase superfamily catalyze the reversible transfer of the gamma-phosphate from ATP to amino acid side chains of proteins. Protein kinase function can be counteracted by the action of phosphoprotein phosphatases. Phosphorylation status of a protein can have profound effects on its activity and interaction with other proteins. An estimated 1 to 3% of functional eukaryotic genes encode protein kinases, suggesting that they are involved in many aspects of cellular regulation and metabolism. In plants, protein phosphorylation has been implicated in responses to many signals, including light, pathogen invasion, hormones, temperature stress, and nutrient deprivation. Activities of several plant metabolic and regulatory enzymes are also controlled by reversible phosphorylation. As might be expected from this diversity of function, there is a large array of different protein kinases. Purification of protein kinases and their subsequent cloning, facilitated by the PCR and advances in homology-based cloning techniques, as well as functional analyses, including complementation of conditional yeast mutants and positional cloning of mutant plant genes, has already led to identification of more than 70 plant protein kinase genes. However, the precise functional roles of specific protein kinases and phosphatases during plant growth and development have been elucidated for only a few.
Amino Acid Sequence↗
Interaction of a protein phosphatase with an Arabidopsis serine-threonine receptor kinase.
A protein phosphatase was cloned that interacts with a serine-threonine receptor-like kinase, RLK5, from Arabidopsis thaliana. The phosphatase, designated KAPP (kinase-associated protein phosphatase), is composed of three domains: an amino-terminal signal anchor, a kinase interaction (KI) domain, and a type 2C protein phosphatase catalytic region. Association of RLK5 with the KI domain is dependent on phosphorylation of RLK5 and can be abolished by dephosphorylation. KAPP may function as a signaling component in a pathway involving RLK5.
Amino Acid Sequence↗
Hemorrhoidal bleeding in chronic spinal cord injury: results of multiple banding.
Most patients with chronic spinal cord injury (SCI) have hemorrhoidal bleeding. 87 banding procedures were performed for bleeding on 62 men with chronic SCI. Multiple bands per session were routinely necessary. Bleeding sites at or distal to the dentate line were also banded. There were no major complications. An outcome questionnaire was completed by 60 subjects (97%). Mean follow-up was one year, minimum one-half year. 73% of patients reported significant reduction in bleeding post-banding, and 20% reported some reduction. A majority of patients felt the procedure was useful or worthwhile overall. Absent sensation allows banding of external hemorrhoids, although symptoms of autonomic hyper-reflexia may occur in patients with lesions at T6 or above. Multiple banding is a safe and effective treatment for hemorrhoidal bleeding in SCI.
Adult↗
Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: relevance to Parkinson's disease.
The mode of cell death in Parkinson's disease (PD) substantia nigra is uncertain. However, evidence is accumulating that certain of the biochemical abnormalities present in PD nigra at the time of death may precipitate apoptosis. We have investigated the mode of death induced by complex I inhibition of dopaminergic cell cultures, and our results suggest that both 1-methyl-4-phenylpyridinium and rotenone cause apoptosis at low concentrations and necrosis at high concentrations. This dose-dependent shift in the mode of cell death induced by these mitochondrial toxins may have important implications for the mechanisms of neuronal cell death in PD.
1-Methyl-4-phenylpyridinium↗
Selection of patients for randomised trials: a study based on the MACOP-B vs CHOP in NHL study.
BACKGROUND: Selection of patients for a clinical trial is affected by awareness of the existence of the trial, interest in the study question and clinical practices and views of the clinicians. AIMS: To investigate the selectivity that may have occurred at Peter MacCallum Cancer Institute (PMCI) during the ANZ Lymphoma Group trial of MACOP-B vs CHOP in non-Hodgkin's lymphoma (NHL). METHODS: NHL patients at PMCI in the study period were assessed against the trial's eligibility criteria. Comparisons were made between eligible (except for consent) non-trial patients and all patients actually randomised into the trial. RESULTS: Of 497 patients presenting during the trial period, 320 (64%) did not meet the specified eligibility criteria, 102 (21%) were unsuitable on other grounds (age and medical) and 75 (15%) were eligible. Of those eligible, 43 (57%) were entered into the trial and 32 (43%) were not. Four non-trial patients had inappropriate application of eligibility criteria and 13 unknown reason. Eligible non-trial patients were similar to trial patients in most patient and tumour characteristics and overall survival. Significantly more non-trial patients had higher stage disease (p = 0.02). More non-trial patients had lower grade histology, but this was not significant. CONCLUSIONS: Physician selectivity occurred with respect to patient entry, but trial and non-trial patients were similar in most characteristics. Eligibility criteria should specify that patients can withstand all trial drugs and patient availability for treatment and follow-up. PMCI trial accural could have been up to 33% greater. These results suggest the trial accrual period could have been 25% shorter. Patient entry into this trial by PMCI clinicians compared favourably with other centres.
Adult↗
Randomized comparison of MACOP-B with CHOP in patients with intermediate-grade non-Hodgkin's lymphoma. The Australian and New Zealand Lymphoma Group.
PURPOSE: To compare complete response rates, time to failure, survival, and toxicity for patients with intermediate-grade non-Hodgkin's lymphoma (NHL) treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) versus those treated with a regimen consisting of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin (MACOP-B), in a multicenter, randomized controlled trial performed by 22 centers of the Australian and New Zealand Lymphoma Group (ANZLG). PATIENTS AND METHODS: Between October 1986 and June 1991, 304 patients were randomized, of whom 236 were eligible for analysis. Eligibility criteria included diffuse small cleaved-cell, diffuse mixed small- and large-cell, follicular large-cell, diffuse large-cell, and large-cell immunoblastic, stages I bulky or II to IV. RESULTS: There was no significant difference in complete response rates (51% for MACOP-B v 59% for CHOP), failure-free survival, or overall survival in the two treatment arms. The rate of death of MACOP-B patients relative to CHOP patients was estimated to be 0.91 (P = .64) when stratified by prognostic group. There were no significant differences between the two regimens in any of the prognostic subgroups. Toxicity was significantly more severe with MACOP-B, particularly cutaneous toxicity, stomatitis, and gastrointestinal ulceration. The average relative dose-intensity (RDI) of MACOP-B was 0.91 and of CHOP was 0.90, indicating good dose delivery in this multicenter group setting. CONCLUSION: CHOP chemotherapy produced results equivalent to those of MACOP-B in patients with intermediate-grade NHL and with significantly fewer toxic complications. Despite relatively poor results in some patient subgroups, CHOP remains the standard chemotherapy for this disease, against which all new regimens should be compared.
Adolescent↗
Inheritance of freezing resistance in tuber-bearing Solanum species: evidence for independent genetic control of nonacclimated freezing tolerance and cold acclimation capacity.
Frost or winter survival is regarded as a complex trait with polygenic inheritance. Two major components of this survival in crop plants are freezing tolerance in the nonacclimated state and cold acclimation capacity. To date researchers have not distinguished the two components as separate heritable traits. The mode of inheritance of these two traits was investigated in F1 and backcross populations of two wild diploid potato species (Solanum commersonii and Solanum cardiophyllum) exhibiting extremes of freezing tolerance and acclimation capacity. Precise assessment of these two traits allowed distinction of small but significant differences among genotypes. The two traits were not correlated in segregating populations, suggesting independent genetic control. Analyses of generation means indicate that all of the variance for acclimation capacity and a major proportion of the variance for the nonacclimated freezing tolerance can be best explained by an additive-dominance model with both traits being partially recessive. Recovery of parental phenotypes in limited populations suggests that both traits are controlled by relatively few genes. To our knowledge this is the first study demonstrating independent genetic control of the two main traits associated with frost or winter survival. Our results show that it should be possible to incorporate these traits from wild germ plasm into cultivated crop plants by independent selection. These results help explain the lack of progress in improving winter survival through field selection. Furthermore, our study demonstrates relative simplicity of the inheritance of cold acclimation, thus providing avenues for understanding the link between biochemical and genetic aspects of low-temperature stress in crop plants.
Journal Article↗
Laparoscopic reduction of acute gastric volvulus.
The traditional surgical treatment of gastric volvulus involves upper abdominal laparotomy with gastric detorsion, fixation, and, when present, repair of associated diaphragmatic hernia. We describe a case of organoaxial gastric volvulus associated with a paraesophageal hernia in a poor risk patient, which was successfully treated with laparoscopic detorsion and percutaneous endoscopic gastropexy. This approach avoided the morbidity of a laparotomy and allowed the rapid recovery of gastric function.
Acute Disease↗