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1.
BMC Public Health ; 22(1): 1945, 2022 10 19.
Article in English | MEDLINE | ID: mdl-36261796

ABSTRACT

BACKGROUND: Suicide is a major issue affecting communities around the world. Community-based suicide prevention approaches can tailor activities at a local level and are recognised as a key component of national suicide prevention strategies. Despite this, research exploring their effects on completed suicides is rare. This study examined the effect of a national program of community suicide prevention networks on suicide rates in catchment areas across Australia. METHODS: Australian suicide data from the National Coronial Information System for 2001-2017 were mapped to geographic catchment areas of community suicide prevention networks and matched control areas with similar characteristics. The effect of network establishment on suicide rates was evaluated using longitudinal models including fixed effects for site type (network or control), time, season, and intervention (network establishment), with site included as a random intercept. RESULTS: Sixty suicide prevention networks were included, servicing areas with a population of 3.5 million. Networks varied in when they were established, ranging from 2007 to 2016. Across the time-period, suicide rates per 100,000 per quarter averaged 3.73 (SD = 5.35). A significant reduction in the suicide rate of 7.0% was found after establishment of networks (IRR = 0.93, 95% CI 0.87 to 0.99, p = .025). CONCLUSION: This study found evidence of an average reduction in suicide rates following the establishment of suicide prevention networks in Australian communities. These findings support the effectiveness of empowering local communities to take action to prevent suicide.


Subject(s)
Suicide Prevention , Humans , Longitudinal Studies , Australia/epidemiology , Community Networks , Research Design
2.
Health Educ Res ; 36(1): 126-139, 2021 03 23.
Article in English | MEDLINE | ID: mdl-33367691

ABSTRACT

teen Mental Health First Aid (teenMHFA) is a school-based mental health program that trains adolescents to support peers who are experiencing mental health problems or crises. The program has been evaluated for adolescents aged 15-18 years as part of a randomized controlled trial, however qualitative feedback from students on their perceptions of the program is yet to be explored. The current study describes the perspectives of students who took part in the trial. Feedback on the perceived strengths and weaknesses of the program was provided by 979 Year 10 students (M = 15.82 years, female = 43.94%, English as a first language = 72.77%) at four government funded public schools in Melbourne, Australia via online surveys. A content and thematic analysis was performed on the data using a six-step process. Students generally found the program relevant and they connected with the visual material, personal stories and interactive activities. Suggestions for improvements included encouraging active student participation in classroom discussion and providing opportunities to practice skills. School-based mental health education can benefit from input from stakeholder perspectives, particularly when designing mental health content for delivery by external trainers.


Subject(s)
Health Education , Schools , Adolescent , Australia , Female , Humans , Peer Group , Program Evaluation , Students
3.
Soc Psychiatry Psychiatr Epidemiol ; 51(9): 1257-64, 2016 09.
Article in English | MEDLINE | ID: mdl-27048265

ABSTRACT

PURPOSE: To assess the associations between beliefs about the dangerousness of people with mental health problems and exposure to media reports of violence or personal experiences of fear, threat or harm. METHODS: Telephone interviews were carried out with 5220 Australians aged 18+. Respondents heard a vignette of a person with depression or early schizophrenia and were asked whether they believed him to be dangerous. Other questions covered past 12-month recall of media reports of violence and mental health problems, contact with and experiences of fear, threat or harm by people with mental health problems. Multinomial logistic regression was used to assess the associations between beliefs about dangerousness and media and these types of contact with people with mental health problems. RESULTS: For the early schizophrenia vignette, recall of media reports and having felt afraid of someone were associated with beliefs about dangerousness. For the depression vignette, media reports about violence and mental health problems or the experiences of feeling afraid or having been threatened or harmed were not strongly associated with beliefs about dangerousness. For both vignettes, knowing someone with a mental health problem and having a higher level of education were associated with less belief in dangerousness. CONCLUSIONS: Media reports may play a greater role in forming attitudes in low prevalence disorders and further efforts to reduce any adverse impact of media reporting should focus on these disorders. The study also supports the effectiveness of contact with people with mental health problems in reducing beliefs about dangerousness.


Subject(s)
Attitude to Health , Dangerous Behavior , Depressive Disorder , Mass Media , Schizophrenia , Social Stigma , Violence , Adolescent , Adult , Australia , Exposure to Violence , Fear , Female , Humans , Logistic Models , Male , Mental Disorders , Mental Health , Middle Aged , Multivariate Analysis , Surveys and Questionnaires , Young Adult
4.
Heredity (Edinb) ; 112(2): 132-42, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24045291

ABSTRACT

Communities of organisms inhabiting extreme terrestrial environments provide a unique opportunity to study evolutionary forces that drive population structure and genetic diversity under the combined challenges posed by multiple geogenic stressors. High abundance of an invasive pantropical earthworm (and the absence of indigenous lumbricid species) in the Furnas geothermal field (Sao Miguel Island, Azores) indicates its remarkable tolerance to high soil temperature, exceptionally high carbon dioxide and low oxygen levels, and elevated metal bioavailability, conditions which are lethal for the majority of terrestrial metazoans. Mitochondrial and nuclear markers were used to analyze the relationship between populations living inside and outside the geothermal field. Results showed that Pontoscolex corethrurus (Annelida, Oligochaeta, Glossoscolecidae) to be a genetically heterogeneous complex within the Sao Miguel landscape and is probably differentiated into cryptic species. The population exposed to the hostile soil conditions within the volcanic caldera possesses the lowest within-population mitochondrial diversity but an unexpectedly high degree of nuclear variability with several loci evidencing positive selection, parameters indicative of a genetically unique population only distantly related to conspecifics living outside the caldera. In conclusion, P. corethrurus inhabiting active volcanic soil is a discrete extremophile population that has evolved by tolerating a mixture of non-anthropogenic chemical and physical stressors.


Subject(s)
Oligochaeta/genetics , Soil , Animals , DNA, Mitochondrial , Genetic Variation , Genetics, Population , Genotype , Molecular Sequence Data , Oligochaeta/classification , Phylogeny
5.
Opt Express ; 21(13): 15102-12, 2013 Jul 01.
Article in English | MEDLINE | ID: mdl-23842297

ABSTRACT

The structures of biological molecules may soon be determined with X-ray free-electron lasers without crystallization by recording the coherent diffraction patterns of many identical copies of a molecule. Most analysis methods require a measurement of each molecule individually. However, current injection methods deliver particles to the X-ray beam stochastically and the maximum yield of single particle measurements is 37% at optimal concentration. The remaining 63% of pulses intercept no particles or multiple particles. We demonstrate that in the latter case single particle diffraction patterns can be extracted provided the particles are sufficiently separated. The technique has the potential to greatly increase the amount of data available for three-dimensional imaging of identical particles with X-ray lasers.

6.
Environ Sci Technol ; 47(2): 1073-81, 2013 Jan 15.
Article in English | MEDLINE | ID: mdl-23198708

ABSTRACT

Understanding the relationships between accumulated metal speciation in cells and tissues of ecologically significant taxa such as earthworms will improve risk assessments. Synchrotron-based µ-focus X-ray spectroscopy was used to detect, localize, and determine ligand-speciation of Zn and Pb in thin sections of two epigeic earthworm species collected from a Pb/Zn-mine soil. The findings indicated that Zn and Pb partition predominantly as typical hard acids (i.e., strong affinities for O-donors) within liverlike chloragocytes. Moreover, Zn speciation was very similar in the chloragog and intestinal epithelia but differed subtly in the kidneylike nephridial tubules; neither Zn nor Pb was detectable in the ventral nerve cord. High resolution X-ray mapping of high pressure-frozen, ultrathin, freeze-substituted sections in a transmission electron microscope (TEM), combined with conventional TEM structural analysis, identified a new cell type packed with highly organized rough endoplasmic reticulum and containing deposits of Cd (codistributed with S); there was no evidence that these cells are major depositories of Zn or Pb. These data may be used in a systems biology approach to assist in the interpretation of metal-evoked perturbations in whole-worm transcriptome and metabolome profiles.


Subject(s)
Cadmium/analysis , Lead/analysis , Oligochaeta/metabolism , Oligochaeta/ultrastructure , Soil Pollutants/analysis , Zinc/analysis , Animals , Cadmium/metabolism , Electron Probe Microanalysis , Environmental Monitoring , Lead/metabolism , Soil/analysis , Soil Pollutants/metabolism , Synchrotrons , X-Ray Absorption Spectroscopy , X-Rays , Zinc/metabolism
7.
Psychol Med ; 42(8): 1753-62, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22166182

ABSTRACT

BACKGROUND: Although mental health information on the internet is often of poor quality, relatively little is known about the quality of websites, such as Wikipedia, that involve participatory information sharing. The aim of this paper was to explore the quality of user-contributed mental health-related information on Wikipedia and compare this with centrally controlled information sources. METHOD: Content on 10 mental health-related topics was extracted from 14 frequently accessed websites (including Wikipedia) providing information about depression and schizophrenia, Encyclopaedia Britannica, and a psychiatry textbook. The content was rated by experts according to the following criteria: accuracy, up-to-dateness, breadth of coverage, referencing and readability. RESULTS: Ratings varied significantly between resources according to topic. Across all topics, Wikipedia was the most highly rated in all domains except readability. CONCLUSIONS: The quality of information on depression and schizophrenia on Wikipedia is generally as good as, or better than, that provided by centrally controlled websites, Encyclopaedia Britannica and a psychiatry textbook.


Subject(s)
Consumer Health Information/standards , Encyclopedias as Topic , Information Dissemination/methods , Internet/standards , Mental Disorders , Textbooks as Topic/standards , Analysis of Variance , Comprehension , Humans , Psychiatry , Reproducibility of Results , Search Engine
8.
Proc Biol Sci ; 276(1658): 789-97, 2009 Mar 07.
Article in English | MEDLINE | ID: mdl-19129111

ABSTRACT

Small incremental biological change, winnowed by natural selection over geological time scales to produce large consequences, was Darwin's singular insight that revolutionized the life sciences. His publications after 1859, including the 'earthworm book', were all written to amplify and support the evolutionary theory presented in the Origin. Darwin was unable to provide a physical basis for the inheritance of favoured traits because of the absence of genetic knowledge that much later led to the 'modern synthesis'. Mistaken though he was in advocating systemic 'gemmules' as agents of inheritance, Darwin was perceptive in seeking to underpin his core vision with concrete factors that both determine the nature of a trait in one generation and convey it to subsequent generations. This brief review evaluates the molecular genetic literature on earthworms published during the last decade, and casts light on the specific aspects of earthworm evolutionary biology that more or less engaged Darwin: (i) biogeography, (ii) species diversity, (iii) local adaptations and (iv) sensitivity. We predict that the current understanding will deepen with the announcement of a draft earthworm genome in Darwin's bicentenary year, 2009. Subsequently, the earthworm may be elevated from the status of a soil sentinel to that elusive entity, an ecologically relevant genetic model organism.


Subject(s)
Gene Expression Regulation/physiology , Genome , Oligochaeta/genetics , Proteins/genetics , Proteins/metabolism , Animals
9.
Science ; 228(4700): 722-4, 1985 May 10.
Article in English | MEDLINE | ID: mdl-2986287

ABSTRACT

Cotton-top tamarins were inoculated with sufficient Epstein-Barr virus to induce multiple tumors in each animal within 14 to 21 days. The tumors consisted of large-cell lymphomas that contained multiple copies of the Epstein-Barr virus genome and generated Epstein-Barr virus-carrying cell lines showing no detectable consistent chromosomal abnormality. Hybridization of tumor DNA with immunoglobulin gene probes revealed that each lymphoma was oligo- or monoclonal in origin and that individual tumors from the same animal arose from different B-cell clones. Thus the virus induced multiple transformation events in tamarins in vivo to cause malignant tumors resembling the Epstein-Barr virus-associated lymphomas of patients with organ transplants.


Subject(s)
B-Lymphocytes/microbiology , Burkitt Lymphoma/microbiology , Animals , Burkitt Lymphoma/genetics , Cell Line , DNA, Neoplasm/genetics , Heart Transplantation , Herpesvirus 4, Human , Humans , Neoplasms, Experimental/genetics , Neoplasms, Experimental/microbiology , Nucleic Acid Hybridization , Saguinus
10.
Epidemiol Psychiatr Sci ; 29: e46, 2019 Aug 09.
Article in English | MEDLINE | ID: mdl-31397261

ABSTRACT

AIMS: The prevalence of common mental disorders has not declined in high-income countries despite substantial increases in service provision. A possible reason for this lack of improvement is that greater willingness to disclose mental disorders might have led to increased reporting of psychiatric symptoms, thus masking reductions in prevalence. This masking hypothesis was tested using data from two trials of interventions that increased willingness to disclose and that also measured symptoms. Both interventions involved Mental Health First Aid (MHFA) training, which is known to reduce stigma, including unwillingness to disclose a mental health problem. METHODS: A cross-lagged panel analysis was carried out on data from two large Australian randomised controlled trials of MHFA training. The first trial involved 1643 high school students in Year 10 (mean age 15.87 years), who were randomised to receive either teen MHFA training or physical first aid training as the control. The second trial involved 608 Australia public servants who were randomised to receive either eLearning MHFA, blended eLearning MHFA or eLearning physical first aid as the control. In both trials, willingness to disclose a mental disorder as described in vignettes and psychiatric symptoms (K6 scale) were measured pre-training, post-training and at 12-month follow-up. RESULTS: Both trials found that MHFA training increased willingness to disclose. However, a cross-lagged panel analysis showed no effect of this change on psychiatric symptom scores. CONCLUSIONS: Greater willingness to disclose did not affect psychiatric symptom scores. Because the trials increased willingness to disclose through a randomly assigned intervention, they provide a strong causal test of the masking hypothesis. It is therefore unlikely that changes in willingness to disclose are masking reductions in prevalence in the population.


Subject(s)
Mental Disorders/psychology , Self Disclosure , Social Stigma , Adolescent , Adult , Attitude to Health , Australia , Health Education , Humans , Students
11.
Epidemiol Psychiatr Sci ; 27(4): 346-356, 2018 08.
Article in English | MEDLINE | ID: mdl-28073386

ABSTRACT

AIMS: The aim of the current study was to carry out a national population-based survey to assess the proportion of people disclosing mental health problems in a variety of settings. A further aim was to explore respondent characteristics associated with disclosure. METHODS: In 2014, telephone interviews were carried out with 5220 Australians aged 18+, 1381 of whom reported a mental health problem or scored highly on a symptom screening questionnaire. Questions covered disclosure of mental health problems to friends, intimate partners, other family members, supervisors or other colleagues in the workplace, teachers, lecturers or other students in the educational institution, health professionals and others in the community. Other than for intimate partners or supervisors, participants were asked whether or not they told everybody, some people or no one. Multinomial logistic regression was used to model the correlates of disclosure in each setting. RESULTS: For friends and family, respondents were more likely to disclose to some people than to everyone or to no one. In most other domains, non-disclosure was most common, including in the workplace, where non-disclosure to supervisors was more likely than disclosure. Disclosure was associated with having received treatment or with support in all settings except healthcare, while it was only associated with discrimination in two settings (healthcare and education). CONCLUSIONS: Disclosure of mental health problems does not appear to be linked to discrimination in most settings, and is typically associated with receiving support. Selective or non-disclosure may be particularly critical in workplaces, education and healthcare settings.


Subject(s)
Disclosure/statistics & numerical data , Family Relations/psychology , Interpersonal Relations , Mental Disorders/psychology , Mental Health/ethnology , Mentally Ill Persons/psychology , Prejudice/psychology , Social Isolation/psychology , Social Stigma , Adolescent , Adult , Aged , Australia/epidemiology , Female , Friends , Health Surveys , Humans , Mental Disorders/epidemiology , Middle Aged , Population Surveillance , Prevalence , Surveys and Questionnaires , Young Adult
12.
Open Biol ; 6(3)2016 Mar.
Article in English | MEDLINE | ID: mdl-26935951

ABSTRACT

Woodlice efficiently sequester copper (Cu) in 'cuprosomes' within hepatopancreatic 'S' cells. Binuclear 'B' cells in the hepatopancreas form iron (Fe) deposits; these cells apparently undergo an apocrine secretory diurnal cycle linked to nocturnal feeding. Synchrotron-based µ-focus X-ray spectroscopy undertaken on thin sections was used to characterize the ligands binding Cu and Fe in S and B cells of Oniscus asellus (Isopoda). Main findings were: (i) morphometry confirmed a diurnal B-cell apocrine cycle; (ii) X-ray fluorescence (XRF) mapping indicated that Cu was co-distributed with sulfur (mainly in S cells), and Fe was co-distributed with phosphate (mainly in B cells); (iii) XRF mapping revealed an intimate morphological relationship between the basal regions of adjacent S and B cells; (iv) molecular modelling and Fourier transform analyses indicated that Cu in the reduced Cu(+) state is mainly coordinated to thiol-rich ligands (Cu-S bond length 2.3 Å) in both cell types, while Fe in the oxidized Fe(3+) state is predominantly oxygen coordinated (estimated Fe-O bond length of approx. 2 Å), with an outer shell of Fe scatterers at approximately 3.05 Å; and (v) no significant differences occur in Cu or Fe speciation at key nodes in the apocrine cycle. Findings imply that S and B cells form integrated unit-pairs; a functional role for secretions from these cellular units in the digestion of recalcitrant dietary components is hypothesized.


Subject(s)
Copper/metabolism , Hepatopancreas/metabolism , Iron/metabolism , Isopoda/metabolism , Animals , B-Lymphocytes/cytology , B-Lymphocytes/metabolism , Binding Sites , Copper/analysis , Hepatopancreas/chemistry , Hepatopancreas/ultrastructure , Iron/analysis , Isopoda/chemistry , Isopoda/ultrastructure , Oxidation-Reduction , Phosphates/analysis , Phosphates/metabolism , Spectrometry, X-Ray Emission , Sulfur/analysis , Sulfur/metabolism
13.
Biochim Biophys Acta ; 1398(3): 294-304, 1998 Jul 09.
Article in English | MEDLINE | ID: mdl-9655922

ABSTRACT

Heavy metal contaminated soils are assessed for specific human health and ecological risk by governmental regulatory agencies utilizing the abundant soil invertebrate, the earthworm, in a biomonitoring process. Fingerprinting the molecular genetic responses resulting from heavy metal exposure facilitates the identification of biomarkers for assessing the impact of such pollution on individual organisms. This paper reports the identification of a novel translationally controlled tumour protein (TCTP) in the earthworm Lumbricus rubellus. In addition to the standard molecular biological technique of differential Southern blotting, a fully quantitative approach (fluorescent microvolume PCR) was performed to assess the specific expression profiles of TCTP in earthworms exposed to different heavy metal regimes. After normalizing with actin as an invariant control, the results showed that TCTP was upregulated by at least a factor of 4 in the population originating from a Pb/Zn/Cd polluted mine, compared to an unpolluted control population. An even more pronounced increase was identified in earthworms native to a Cu polluted mine, where TCTP increased 335-fold. TCTP copies in earthworms exposed to artificial soil with a single stressor (Cd) were 14 times higher than in the appropriate control earthworms (maintained on artificial soil without Cd). The data presented are novel in two ways: first, they provide evidence for an upregulation that is induced by heavy metals (especially copper); second, they show that TCTP can also be under transcriptional control, therefore upregulation is not limited to translational modifications as TCTP's nomenclature suggests.


Subject(s)
Biomarkers, Tumor , Calcium-Binding Proteins/genetics , Gene Expression Regulation , Metals, Heavy , Neoplasm Proteins/genetics , Protein Biosynthesis , Amino Acid Sequence , Animals , Base Sequence , DNA, Complementary , Humans , Molecular Sequence Data , Oligochaeta , Sequence Homology, Amino Acid , Tumor Protein, Translationally-Controlled 1
14.
Biochim Biophys Acta ; 1489(2-3): 467-73, 1999 Dec 23.
Article in English | MEDLINE | ID: mdl-10673053

ABSTRACT

We report the identification of two earthworm cyclophilin genes, which resemble the cytosolic cyclophilin-A and the signal sequence containing cyclophilin-B. Using fully quantitative PCR we were able to assess the transcript regulation of both cyclophilin isoforms, as well as a further independent control gene (actin), during exposure to heavy metals. Whilst the expression of cyclophilin-B and actin remained exceptionally constant, cyclophilin-A was up-regulated 38-fold. This intriguing observation has profound implications regarding cyclophilin's use as an invariant control and highlights the fact that it is essential to treat cyclophilin isoforms as separate entities, rather than one functional unit.


Subject(s)
Cyclophilins , Immunophilins/genetics , Metals, Heavy/pharmacology , Oligochaeta/genetics , Peptidylprolyl Isomerase/genetics , Protein Isoforms/pharmacology , Amino Acid Sequence , Animals , Base Sequence , DNA Primers , DNA, Complementary , Humans , Molecular Sequence Data , Phylogeny , Sequence Homology, Amino Acid
15.
FEBS Lett ; 431(3): 437-42, 1998 Jul 24.
Article in English | MEDLINE | ID: mdl-9714559

ABSTRACT

Combining standard gel chromatographic techniques and novel molecular methodologies (Directed Differential Display and quantitative PCR), it has been possible to isolate and sequence two isoforms of the first true earthworm metallothionein. Both proteins are characteristically high in cysteine residues and possess no significant aromatic residues. Metal responsiveness was confirmed by determining metallothionein specific expression profiles in earthworms exposed to soils of differing heavy metal concentrations. Analysis of the derived amino acid sequence of isoform 2 identified two putative N-glycosylation signal sequences, suggesting that the two isoforms may have different subcellular distributions and functions. Possible implications for intracellular metal trafficking are discussed.


Subject(s)
Metallothionein/metabolism , Oligochaeta/metabolism , Amino Acid Sequence , Animals , Cadmium/metabolism , Chromatography, Gel/methods , Cloning, Molecular , Metallothionein/chemistry , Metallothionein/isolation & purification , Molecular Sequence Data , Polymerase Chain Reaction , Protein Binding
16.
J Immunol Methods ; 108(1-2): 231-6, 1988 Apr 06.
Article in English | MEDLINE | ID: mdl-2832478

ABSTRACT

A rapid and efficient procedure for the isolation of Epstein-Barr (EB) virus membrane glycoprotein gp340 has been developed. The mild, two step method consisted of anion exchange chromatography of B95-8 cell membrane detergent extracts followed by further purification by gel filtration. Production of homogeneous gp340 was achieved routinely with recoveries of at least 35% from starting material. The purified molecule, when injected into mice with a synthetic muramyl dipeptide adjuvant, N-acetylmuramyl-L-threonyl-D-isoglutamine ((Thr1)MDP), elicited high titres of EB virus-neutralizing antibody.


Subject(s)
Antigens, Surface/isolation & purification , Antigens, Viral/isolation & purification , Chromatography, High Pressure Liquid/methods , Herpesvirus 4, Human/immunology , Membrane Glycoproteins/isolation & purification , Viral Matrix Proteins , Animals , Antibodies, Viral/analysis , Antigens, Viral/immunology , Chemical Fractionation , Chromatography, Gel , Chromatography, Ion Exchange , Female , Mice , Mice, Inbred BALB C
17.
J Immunol Methods ; 77(1): 25-36, 1985 Feb 28.
Article in English | MEDLINE | ID: mdl-2579161

ABSTRACT

A purification method has been elaborated to isolate Epstein-Barr (EB) virus membrane antigen, gp340, in milligram amounts. The gp340 was prepared from detergent extracts of B95-8 cells by affinity chromatography with a monoclonal antibody immunoabsorbent. Bound material was eluted and the eluate, consisting of 50% gp340, was then fractionated by gel filtration. The final gp340 product was antigenically active and 95% pure. The purification method was found to be rapid and reproducible with no loss of the ability of the immunoabsorbent to retain gp340 after repeated elution. The procedure provides suitable material to permit the detailed structural analysis of gp340 necessary for both vaccine design and for the investigation of the role of gp340 in immunity to EB virus infection.


Subject(s)
Antigens, Viral/analysis , Herpesvirus 4, Human/immunology , Membrane Proteins/isolation & purification , Viral Proteins/isolation & purification , Antibodies, Monoclonal , Chromatography, Gel , Epitopes , Glycoproteins/isolation & purification , Immunosorbent Techniques
18.
J Immunol Methods ; 178(2): 195-200, 1995 Jan 27.
Article in English | MEDLINE | ID: mdl-7836781

ABSTRACT

32 monoclonal antibodies reactive with human CD antigens were tested against tamarin peripheral blood lymphocytes, ConA blasts and lymphoblastoid B cell lines derived from tamarin cells. Reagents that cross-react with MHC class I and II, B cells (CD20, -21 and -23), monocytes (CD14) and NK cells (CD16, -56) have been identified. In addition monoclonals that cross-react with T cells (CD2, CD3), the CD4/CD8 subsets of T cells and the IL-2 receptor (CD25) are reported. A monoclonal against the beta chain of LFA-1 (CD18) cross-reacted strongly, but there was only a very poor cross-reaction with a monoclonal against the alpha chain of CD11a. Two monoclonals tested against ICAM-1(CD54) were negative.


Subject(s)
Antibodies, Monoclonal/immunology , Antigens, CD/immunology , Lymphocytes/immunology , Saguinus/immunology , Animals , Cells, Cultured , Concanavalin A/pharmacology , Cross Reactions/immunology , Flow Cytometry , Humans , Lymphocyte Activation/immunology
19.
Biochem Pharmacol ; 45(12): 2373-80, 1993 Jun 22.
Article in English | MEDLINE | ID: mdl-7687130

ABSTRACT

A comparison of the effects of various phosphodiesterase (PDE) inhibitors upon cellular cAMP levels was undertaken in human neuroblastoma SH-SY5Y cells. When inhibitors such as rolipram and Ro 20 1724 (selective for the low Km cAMP-specific PDE) were used, cAMP levels were seen to rise dramatically under basal (< or = 60 fold) or forskolin-stimulated (< or = 200 fold) conditions. However, the non-selective PDE inhibitor isobutylmethylxanthine (IBMX) was 7-18% as effective as these other agents even at 1 mM. The poor efficacy of IBMX was not attributable to concomitant increases in cGMP, to alterations in cAMP egress or to a lack of sensitivity of the cellular PDEs to IBMX inhibition. In additivity experiments, IBMX potently and rapidly reduced cAMP that had accumulated after rolipram treatment. The fact that the agonist 2-chloroadenosine can enhance cAMP accumulation in these cells, and that cAMP elevated by rolipram or forskolin can be reduced by adenosine deaminase and theophylline suggest that cell-derived adenosine enhances cAMP in these cells in an autocrine fashion. Since IBMX is an adenosine receptor antagonist, it is suggested that its blockade of endogenous adenosine effects is at least partly responsible for its poor response when compared to other PDE inhibitors which are weaker adenosine receptor antagonists. These results forewarn against assuming that similar levels of cAMP accumulate after application of PDE inhibitors in these cells.


Subject(s)
1-Methyl-3-isobutylxanthine/pharmacology , Cyclic AMP/analysis , Neuroblastoma/metabolism , Phosphodiesterase Inhibitors/pharmacology , 2-Chloroadenosine/pharmacology , Adenosine/antagonists & inhibitors , Adenylyl Cyclase Inhibitors , Cell Line/drug effects , Cell Line/metabolism , Colforsin/pharmacology , Dose-Response Relationship, Drug , Humans , Pyrrolidinones/pharmacology , Rolipram , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/metabolism
20.
Org Lett ; 2(17): 2571-3, 2000 Aug 24.
Article in English | MEDLINE | ID: mdl-10990399

ABSTRACT

[reaction: see text]An efficient formal synthesis of the potent protein kinase C inhibitor (-)-balanol that relies on a modified asymmetric aminohydroxylation of the alpha,beta-unsaturated aryl ester (1) is reported. The aryl ester functionality and the dihydroquinyl alkaloid ligand system (DHQ)2-AQN are used to control the regio- and enantioselectivity of the process.


Subject(s)
Azepines/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Hydroxybenzoates/chemical synthesis , Protein Kinase C/antagonists & inhibitors , Amination , Hydroxylation , Magnetic Resonance Spectroscopy
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