PubMed Health⌕ Search

Biomedical subjects

J T Hancock

Publications and source records attributed to J T Hancock.

At least 19 recordsLinked to original sources
PubMed2006

Short-term psychodynamic psychotherapies for common mental disorders.

BACKGROUND: Over the past 40 years, short-term psychodynamic psychotherapies (STPP) for a broad range of psychological and somatic disorders have been developed and studied. Four published meta-analyses of STPP, using different methods and samples, have found conflicting results. OBJECTIVES: This review evaluated the efficacy of STPP relative to minimal treatment and non-treatment controls for adults with common mental disorders. SEARCH STRATEGY: We searched CCDANCTR-Studies and CCDANCTR-References on 25/4/2005, CENTRAL, MEDLINE, CINAHL, EMBASE, PsycINFO, DARE and Biological Abstracts were also searched. We contacted triallists and checked references from papers retrieved. SELECTION CRITERIA: All randomised controlled trials (RCT) of adults with common mental disorders, in which a brief psychodynamic therapy lasting less than 40 hours in total, and provided in individual format, were included. DATA COLLECTION AND ANALYSIS: Three reviewers working in pairs evaluated studies. Studies were selected only if pairs of reviewers agreed they met inclusion criteria. A third reviewer was consulted if two reviewers could not reach consensus. Data were collected and entered into Review Manager. Study quality was assessed and scored by pairs of raters. Publication bias was assessed using a funnel plot. Sensitivity analyses were also conducted. MAIN RESULTS: 23 studies of 1431 randomised patients with common mental disorders were included. These studies evaluated STPP for general, somatic, anxiety, and depressive symptom reduction, as well as social adjustment. Outcomes for most categories of disorder suggested significantly greater improvement in the treatment versus the control groups, which were generally maintained in medium and long term follow-up. However, only a small number of studies contributed data for each category of disorder, there was significant heterogeneity between studies, and results were not always maintained in sensitivity analyses. AUTHORS' CONCLUSIONS: STPP shows promise, with modest to moderate, often sustained gains for a variety of patients. However, given the limited data and heterogeneity between studies, these findings should be interpreted with caution. Furthermore, variability in treatment delivery and treatment quality may limit the reliability of estimates of effect for STPP. Larger studies of higher quality and with specific diagnoses are warranted.

Humans↗
PubMed2001

Does the redox status of cytochrome C act as a fail-safe mechanism in the regulation of programmed cell death?

It has now become recognized that one of the key events in the induction of apoptosis, or programmed cell death, in both plants and animals is the release of cytochrome c from mitochondria. It is also known that oxidative stress imposed on cells can have a profound effect on the onset or progression of apoptosis. Here, we discuss how the redox status of cytochrome c, and thus its structure, can be altered by the presence of reactive oxygen species (ROS) and reduced glutathione (GSH). We suggest that cytochrome c will only induce programmed cell death if present in the cytoplasm in the oxidized state, and that the presence of high levels of cytoplasmic GSH maintain cytochrome c in an inactive (reduced) state, thus behaving as a fail-safe mechanism if cytochrome c is released by mitochondria when programmed cell death is not the required outcome. If the redox status of the cell is disturbed however, perhaps in the presence of hydrogen peroxide, GSH concentrations will drop, the cellular E(h) will rise, and cytochrome c will tend towards the oxidized state, allowing programmed cell death to proceed. Therefore, we propose that the redox state of cytoplasmic cytochrome c may be a key regulator of programmed cell death.

Animals↗
PubMed2001

Role of reactive oxygen species in cell signalling pathways.

Reactive oxygen species (ROS) were originally thought to only be released by phagocytic cells during their role in host defence. It is now clear that ROS have a cell signalling role in many biological systems, both in animals and in plants. ROS induce programmed cell death or necrosis, induce or suppress the expression of many genes, and activate cell signalling cascades, such as those involving mitogen-activated protein kinases.

Animals↗
PubMed2001

Harpin induces activation of the Arabidopsis mitogen-activated protein kinases AtMPK4 and AtMPK6.

Mitogen-activated protein kinases (MAPKs) are key enzymes that mediate adaptive responses to various abiotic and biotic stresses, including pathogen challenge. The proteinaceous bacterial elicitor harpin (secreted by Pseudomonas syringae pv syringae) activates two MAPKs in suspension cultures of Arabidopsis var. Landsberg erecta. In this study, we show that harpin and exogenous hydrogen peroxide (H(2)O(2)) activate myelin basic protein kinases in Arabidopsis leaves. Using anti-AtMPK4 and anti-AtMPK6 antibodies, we identify the harpin-activated MAPKs in both leaves and suspension cultures as AtMPK4 and AtMPK6, and show that H(2)O(2), generated by Arabidopsis cells in response to challenge with harpin, activates only AtMPK6. However, treatments with catalase, which removes H(2)O(2), or diphenylene iodonium, which inhibits superoxide and H(2)O(2) production, do not inhibit harpin-induced activation of AtMPK4 or AtMPK6. In addition, activation of AtMPK4 but not AtMPK6 is inhibited by the MAPK kinase inhibitor PD98059. Neither harpin nor H(2)O(2) has any effect on AtMPK4 or AtMPK6 gene expression. In addition, the expression of AtMEKK1, AtMEK1, or AtMKK2, previously shown to be potential functional partners of AtMPK4, were not affected by either harpin or H(2)O(2) treatments. These data suggest that harpin activates several signaling pathways, one leading to stimulation of the oxidative burst and others leading to the activation of AtMPK4 or AtMPK6.

Arabidopsis↗
PubMed2001

Regulation of the Arabidopsis transcriptome by oxidative stress.

Oxidative stress, resulting from an imbalance in the accumulation and removal of reactive oxygen species such as hydrogen peroxide (H(2)O(2)), is a challenge faced by all aerobic organisms. In plants, exposure to various abiotic and biotic stresses results in accumulation of H(2)O(2) and oxidative stress. Increasing evidence indicates that H(2)O(2) functions as a stress signal in plants, mediating adaptive responses to various stresses. To analyze cellular responses to H(2)O(2), we have undertaken a large-scale analysis of the Arabidopsis transcriptome during oxidative stress. Using cDNA microarray technology, we identified 175 non-redundant expressed sequence tags that are regulated by H(2)O(2). Of these, 113 are induced and 62 are repressed by H(2)O(2). A substantial proportion of these expressed sequence tags have predicted functions in cell rescue and defense processes. RNA-blot analyses of selected genes were used to verify the microarray data and extend them to demonstrate that other stresses such as wilting, UV irradiation, and elicitor challenge also induce the expression of many of these genes, both independently of, and, in some cases, via H(2)O(2).

Adaptation, Physiological↗
PubMed2000

NADPH oxidase: a universal oxygen sensor?

NADPH oxidase is classically regarded as a key enzyme of neutrophils, where it is involved in the pathogenic production of reactive oxygen species. However, NADPH oxidase-like enzymes have recently been identified in non-neutrophil cells, supporting a separate role for NADPH-oxidase derived oxygen species in oxygen sensitive processes. This article reviews the current literature surrounding the potential role of NADPH oxidase in the oxygen sensing processes which underlie hypoxic pulmonary vasoconstriction, systemic vascular smooth muscle proliferation, carotid and airways chemoreceptor activation, erythropoietin gene expression, and oxytropic responses of plant cells.

Animals↗
PubMed2000

Hydrogen peroxide-induced gene expression in Arabidopsis thaliana.

Hydrogen peroxide (H(2)O(2)) is generated in plants after exposure to a variety of biotic and abiotic stresses, and has been shown to induce a number of cellular responses. Previously, we showed that H(2)O(2) generated during plant-elicitor interactions acts as a signaling molecule to induce the expression of defense genes and initiate programmed cell death in Arabidopsis thaliana suspension cultures. Here, we report for the first time the identification by RNA differential display of four genes whose expression is induced by H(2)O(2). These include genes that have sequence homology to previously identified Arabidopsis genes encoding a late embryogenesis-abundant protein, a DNA-damage repair protein, and a serine/threonine kinase. Their putative roles in H(2)O(2)-induced defense responses are discussed.

Amino Acid Sequence↗
PubMed2000

Proctolin antagonists bind to [(3)H]proctolin binding sites in the locust hindgut.

Proctolin caused dose-dependent (1-200 nM) contraction of the isolated hindgut of S. gregaria which was abolished by [alpha-methyl-L-tyrosine(2)]-proctolin (1 microM). In comparison, cycloproctolin (5 microM) reduced the proctolin maximum response by 41%. Hindgut homogenates contained [(3)H]proctolin binding sites with a K(d) value of 660 nM, a B(max) value of 23.8 pmol/mg protein and a Hill coefficient of 0.934. Cycloproctolin (IC(50,) 220 nM; K(i), 204 nM), unlabeled proctolin (IC(50) 680 nM) and [alpha-methyl-L-tryosine(2)]-proctolin (IC(50) 3.1 microM, K(i), 2.9 microM) but not SchistoFLRFamide (1 nM-10 microM) were capable of displacing bound [(3)H]proctolin.

Animals↗
PubMed2000

NO way back: nitric oxide and programmed cell death in Arabidopsis thaliana suspension cultures.

Recent research has implicated nitric oxide (NO) in the induction of the hypersensitive response (HR) during plant-pathogen interactions. Here we demonstrate that Arabidopsis suspension cultures generate elevated levels of NO in response to challenge by avirulent bacteria, and, using NO donors, show that these elevated levels of NO are sufficient to induce cell death in Arabidopsis cells independently of reactive oxygen species (ROS). We also provide evidence that NO-induced cell death is a form of programmed cell death (PCD), requiring gene expression, and has a number of characteristics of PCD of mammalian cells: NO induced chromatin condensation and caspase-like activity in Arabidopsis cells, while the caspase-1 inhibitor, Ac-YVAD-CMK, blocked NO-induced cell death. A well-established second messenger mediating NO responses in mammalian cells is cGMP, produced by the enzyme guanylate cyclase. A specific inhibitor of guanylate cyclase blocked NO-induced cell death in Arabidopsis cells, and this inhibition was reversed by the cell-permeable cGMP analogue, 8Br-cGMP, although 8Br-cGMP alone did not induce cell death or potentiate NO-induced cell death. This suggests that cGMP synthesis is required but not sufficient for NO-induced cell death in Arabidopsis. In-gel protein kinase assays showed that NO activates a potential mitogen-activated protein kinase (MAPK), although a specific inhibitor of mammalian MAPK activation, PD98059, which blocked H2O2-induced cell death, did not inhibit the effects of NO.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Harpin induces mitogen-activated protein kinase activity during defence responses in Arabidopsis thaliana suspension cultures.

Elicitation of Arabidopsis thaliana (L.) Heynh. suspension cultures with the bacterial protein harpin (from Pseudomonas syringae pv. syringae) induced the activation of two kinases of 39 and 44 kDa, as demonstrated by in-gel kinase assays using myelin basic protein (MBP) as a substrate. Both these kinases appeared to be tyrosine-phosphorylated upon activation, as demonstrated by treatment with tyrosine phosphatase and immunoprecipitation using an anti-phosphotyrosine monoclonal antibody. An inhibitor of mammalian mitogen-activated protein kinase (MAPK) activation, PD98059, inhibited harpin-induced MBPK activation, but did not inhibit the activity of these kinases. PD98059 also inhibited harpin-induced programmed cell death and defence gene expression, suggesting the involvement of harpin-induced MAPKs in defence responses in Arabidopsis thaliana.

Apoptosis↗
PubMed1998

Harpin and hydrogen peroxide both initiate programmed cell death but have differential effects on defence gene expression in Arabidopsis suspension cultures.

Programmed cell death is increasingly viewed as a key component of the hypersensitive disease resistance response of plants. The generation of reactive oxygen species (ROS) such as H2O2 triggers a cell death programme in Arabidopsis suspension cultures following challenge with the bacterial elicitor harpin. Both harpin and exogenous H2O2 initiate a cell death pathway that requires gene expression, and also act as signalling molecules to induce the expression of plant defence genes encoding enzymes such as phenylalanine ammonia-lyase (PAL), glutathione S-transferase (GST) and anthranilate synthase (ASA1), an enzyme of phytoalexin biosynthesis in Arabidopsis. H2O2 induces the expression of PAL1 and GST but not that of ASA1. Harpin initiates two signalling pathways, one leading to increased ROS generation and expression of PAL1 and GST mRNA, and another leading to increased GST and ASA1 expression, independent of H2O2.

Anthranilate Synthase↗
PubMed1998

NADPH oxidase of chondrocytes contains an isoform of the gp91phox subunit.

Previously it has been reported that chondrocytic cells produce oxygen free radicals and express the cytosolic components of NADPH oxidase. Here we report the expression of large subunit of the flavocytochrome of NADPH oxidase in chondrocytes and, further, show that the cDNA sequence contains three single base pair differences compared with the phagocyte gp91phox gene sequence. These base-pair differences may account for the different activity profiles reported between phagocytic and non-phagocytic cells.

Amino Acid Sequence↗
PubMed1998

In situ detection of superoxide anions within porcine articular cartilage.

Cartilage was isolated from pig articular joints, and the production of reactive oxygen species (ROS) by chondrocytes embedded within the cartilage was assessed by two methods: the reduction of nitro blue tetrazolium and by the use of diaminobenzidine in the presence of manganese ions. Little constitutive generation of ROS was seen, but it could be detected after the addition of the calcium ionophore ionomycin. Further, the response seen was extremely heterogeneous; some cells showed a far greater release of ROS than others. Cells arranged in the columnar arrays of the deep zone were the most active, while those furthest from the cartilage/bone interface (i.e. nearer to the outer face of the cartilage) were unresponsive. Chondrocytes cultured in alginate beads also showed a similar heterogeneity in their response, suggesting that the isolation of these cells and the measurement of ROS production in a population is not representative of the true situation.

Animals↗
PubMed1997

Detection of superoxide and NADPH oxidase in porcine articular chondrocytes.

Porcine articular chondrocytes have the capacity to release superoxide in response to the addition of the calcium ionophore ionomycin in a concentration-dependent manner. This activity was not stimulated by the addition of fMetLeuPhe or the kinase activator phorbol myristate acetate (PMA). However, this release of superoxide was inhibited by iodonium diphenyl (IDP), suggesting the involvement of NADPH oxidase. Reverse transcriptase polymerase chain reaction (RT-PCR) using oligonucleotides designed against the known sequences for the human phagocyte NADPH oxidase showed the expression of p22-phox, p40-phox, and p47-phox mRNA, while Western blot analysis of chondrocyte extracts using polyclonal antisera raised against the human phagocyte NADPH oxidase suggested the presence of the p67-phox polypeptide. These results suggest that porcine articular chondrocytes can release reactive oxygen species using a NADPH oxidase-like complex.

Animals↗
PubMed1997

Detection of protein and mRNA of various components of the NADPH oxidase complex in an immortalized human chondrocyte line.

The immortalized human chondrocyte cell line C-20/A4 has the ability to produce superoxide constitutively at low levels of 5.4 x 10(-2) nmol/min/10(6) cells (S.E.M. = +/-0.5, n = 30) and at raised levels upon stimulation with ionomycin and phorbol 12-myristate 13-acetate. Priming and anti-priming effects of interleukin (IL)-1 beta and IL-4, respectively, are also demonstrated. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification using oligonucleotide primers to components of the NADPH oxidase enzyme complex showed mRNA expression of p22-phox, p40-phox and p47-phox. Western blot analysis using polyclonal antisera indicated the presence of the p47-phox p67-phox polypeptide components. These results show that the C-20/A4 cells contain an NADPH oxidase-like complex, similar to that found in other cell types, which produces superoxide anions.

Base Sequence↗
PubMed1997

Superoxide, hydrogen peroxide and nitric oxide as signalling molecules: their production and role in disease.

All cells rely on a complex interplay of both extracellular and intracellular signals to control their metabolism, growth and differentiation. Recent evidence shows that several free radicals and their derivatives are able to act as signalling molecules. However, these molecules are inherently reactive towards biological materials such as proteins, lipids and DNA. In fact, the destructive power of these compounds appears to be harnessed and used by organisms to destroy both invading pathogens and tumour cells. Therefore, their use as signals seems to be a puzzle. Here, their production, role in signalling, and involvement in some diseases are discussed.

Humans↗
PubMed1996

Generation of active oxygen in elicited cells of Arabidopsis thaliana is mediated by a NADPH oxidase-like enzyme.

Suspension-cultured cells of Arabidopsis thaliana generated active oxygen species (AOS) (measured by luminol-dependent chemiluminescence) following challenge with the bacterial protein elicitor harpin or the protein kinase activator phorbol 12-myristate 13-acetate. These responses were blocked by inhibitors of superoxide dismutase (SOD), NADPH oxidase and protein kinase. Harpin treatment also resulted in an increase in cell death, a response reduced by inhibitors of AOS generation or AOS scavengers. Extracellular SOD activity was found to be present in cell culture medium. Immunoblotting of Arabidopsis extracts revealed the presence of proteins immunologically related to the human neutrophil NADPH oxidase complex, and cell-free reconstitution assays showed that human neutrophil cytosol combined with Arabidopsis membranes could initiate superoxide generation. These data suggest that the enzyme catalysing the generation of superoxide in elicited Arabidopsis cells is similar to the mammalian NADPH oxidase and that a signalling cascade leading to AOS generation involves protein phosphorylation.

Arabidopsis↗