Fisher profiles and perceptions of sea turtle-fishery interactions: case study of East Coast Peninsular Malaysia

The paper focuses on coastal fisheries, particularly examining sea turtle-fishery interactions and determining the socioeconomic profile and perception of local fishers about sea turtle issues along the East Coast of Peninsular Malaysia.Turtle fisheries, Nature conservation, Coastal fisheries, Man-induced effects, ISEW, Malaysia, Malaya, Pahang, Malaysia, Malaya, Kelantan, Malaysia, Malaya, Terengganu,

Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines

<p>Abstract</p> <p>Background</p> <p>An organic extract of the recreational herb khat (<it>Catha edulis </it>Forsk.) triggers cell death in various leukemia cell lines <it>in vitro</it>. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid leukemia cell lines to elucidate mechanisms of toxicity.</p> <p>Results</p> <p>Khat had a profound effect on MOLM-13 cells inducing mitochondrial damage, chromatin margination and morphological features of autophagy. The effects of khat on mitochondrial ultrastructure in MOLM-13 correlated with strongly impaired routine respiration, an effect neither found in the khat-resistant MV-4-11 cells nor in camptothecin treated cells. Enforced expression of anti-apoptotic Bcl-2 protein provided protection against camptothecin-induced cell death and partly against khat toxicity. Khat-induced cell death in MOLM-13 cells included reduced levels of anti-apoptotic Mcl-1 protein, while both khat and camptothecin induced c-FLIP_Lcleavage and procaspase-8 activation.</p> <p>Conclusion</p> <p>Khat activated a distinct cell death pathway in sensitive leukemic cells as compared to camptothecin, involving mitochondrial damage and morphological features of autophagy. This suggests that khat should be further explored in the search for novel experimental therapeutics.</p

Caspase I-related protease inhibition retards the execution of okadaic acid- and camptothecin-induced apoptosis and PAI-2 cleavage, but not commitment to cell death in HL-60 cells

We have previously reported that the putative cytoprotective protease inhibitor, plasminogen activator inhibitor type 2 (PAI-2), is specifically cleaved during okadaic acid-induced apoptosis in a myeloid leukaemic cell line (Br J Cancer (1994) 70: 834–840). HL-60 cells exposed to okadaic acid and camptothecin underwent morphological and biochemical changes typical of apoptosis, including internucleosomal DNA fragmentation and PAI-2 cleavage. Significant endogenous PAI-2 cleavage was observed 9 h after exposure to okadaic acid; thus correlating with other signs of macromolecular degradation, like internucleosomal DNA fragmentation. In camptothecin-treated cells, PAI-2 cleavage was an early event, detectable after 2 h of treatment, and preceding internucleosomal DNA fragmentation. The caspase I selective protease inhibitor, YVAD-cmk, inhibited internucleosomal DNA fragmentation and PAI-2 cleavage of okadaic acid and camptothecin-induced apoptotic cells. YVAD-cmk rather sensitively and non-toxically inhibited camptothecin-induced morphology, but not okadaic acid-induced morphology. In in vitro experiments recombinant PAI-2 was not found to be a substrate for caspase I. The results suggest that caspase I selective protease inhibition could antagonize parameters coupled to the execution phase of okadaic acid- and camptothecin-induced apoptosis, but not the commitment to cell death. © 1999 Cancer Research Campaig

Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during chemotherapy of acute myeloid leukemia

<p>Abstract</p> <p>Background</p> <p>The molecular changes <it>in vivo </it>in acute myeloid leukemia cells early after start of conventional genotoxic chemotherapy are incompletely understood, and it is not known if early molecular modulations reflect clinical response.</p> <p>Methods</p> <p>The gene expression was examined by whole genome 44 k oligo microarrays and 12 k cDNA microarrays in peripheral blood leukocytes collected from seven leukemia patients before treatment, 2–4 h and 18–24 h after start of chemotherapy and validated by real-time quantitative PCR. Statistically significantly upregulated genes were classified using gene ontology (GO) terms. Parallel samples were examined by flow cytometry for apoptosis by annexin V-binding and the expression of selected proteins were confirmed by immunoblotting.</p> <p>Results</p> <p>Significant differential modulation of 151 genes were found at 4 h after start of induction therapy with cytarabine and anthracycline, including significant overexpression of 31 genes associated with p53 regulation. Within 4 h of chemotherapy the BCL2/BAX and BCL2/PUMA ratio were attenuated in proapoptotic direction. FLT3 mutations indicated that non-responders (5/7 patients, 8 versus 49 months survival) are characterized by a unique gene response profile before and at 4 h. At 18–24 h after chemotherapy, the gene expression of p53 target genes was attenuated, while genes involved in chemoresistance, cytarabine detoxification, chemokine networks and T cell receptor were prominent. No signs of apoptosis were observed in the collected cells, suggesting the treated patients as a physiological source of pre-apoptotic cells.</p> <p>Conclusion</p> <p>Pre-apoptotic gene expression can be monitored within hours after start of chemotherapy in patients with acute myeloid leukemia, and may be useful in future determination of therapy responders. The low number of patients and the heterogeneity of acute myeloid leukemia limited the identification of gene expression predictive of therapy response. Therapy-induced gene expression reflects the complex biological processes involved in clinical cancer cell eradication and should be explored for future enhancement of therapy.</p

Reliability of MRI findings in candidates for lumbar disc prosthesis

Introduction: Limited reliability data exist for localised magnetic resonance imaging (MRI) findings relevant to planning of treatment with lumbar disc prosthesis and later outcomes. We assessed the reliability of such findings in chronic low back pain patients who were accepted candidates for disc prosthesis. Methods: On pretreatment MRI of 170 patients (mean age 41 years; 88 women), three experienced radiologists independently rated Modic changes, disc findings and facet arthropathy at L3/L4, L4/L5 and L5/S1. Two radiologists rerated 126 examinations. For each MRI finding at each disc level, agreement was analysed using the kappa statistic and differences in prevalence across observers using a fixed effects model. Results: All findings at L3/L4 and facet arthropathy at L5/S1 had a mean prevalence <10% across observers and were not further analysed, ensuring interpretable kappa values. Overall interobserver agreement was generally moderate or good (kappa 0.40–0.77) at L4–S1 for Modic changes, nucleus pulposus signal, disc height (subjective and measured), posterior high-intensity zone (HIZ) and disc contour, and fair (kappa 0.24) at L4/L5 for facet arthropathy. Posterior HIZ at L5/S1 and severely reduced subjective disc height at L4/L5 differed up to threefold in prevalence between observers (p< 0.0001). Intraobserver agreement was mostly good or very good (kappa 0.60–1.00). Conclusion: In candidates for disc prosthesis, mostly moderate interobserver agreement is expected for localised MRI findings