Leading Causes of Death among Asian American Subgroups (2003–2011)

Background

Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups.

Methods and Findings

We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer’s disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs.

Conclusions

Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.     

Cloning and expression of human islet amyloid polypeptide in cultured cells

Efforts to clone amyloidogenic proteins in the cells often have resulted in cell death. We report successful cloning and expression of recombinant human islet amyloid polypeptide (hIAPP) in cultured mammalian cells. Amylin gets secreted, forms fibrils that are toxic to target cells like beta cells of rat and human. The study involves cloning of full-length amylin in fluorescent protein vector followed by transfection into mammalian cells. The transfected cells with recombinant human amylin, secrete the translated protein corresponding to 37-amino acid native mature IAPP. The mature IAPP secreted out of the cell is purified and characterized by MALDI-TOF/TOF-MS and Western blotting. Purified IAPP forms fibrils as seen by Thioflavin-T fluorescence and AFM, and these fibrils were cytotoxic towards pancreatic cell line RIN5mf cells.     

Recombinant pp60 c-src from Baculovirus-Infected Insect Cells: Purification and Characterization

A simple and effective method has been developed to purify the recombinant protein tyrosine kinase pp60^c-^src from a baculovirus-insect cell expression system. The procedure includes affinity chromatography and HPLC. Milligram quantities of protein have been isolated with an activity of 3.9 μmol/min/mg protein using the substrate poly E₄Y. This specific activity is many times higher than any published protocol. The enzyme is stable for months when stored in buffered 10% glycerol at ?70°C. This purification technique is compared to the immuno-affinity technique which is widely used for this enzyme. Enzyme kinetics were characterized with respect to substrate specificity, the effect of temperature, ionic strength, pH, and Mg⁺² versus Mn⁺² ions. Similar to the enzyme expressed in human cells, the recombinant enzyme demonstrated a higher Vmax and substrate specificity for poly E₄Y over 5V-Agt-II. An activation energy of 14.2 kcal/mol was determined. Inhibition by increasing ionic strength is mostly due to an increase in Km for the poly E₄Y substrate and hence was substrate dependent. The Km(ATP) was pH dependent while the Km(poly E₄Y) was pH independent.     

Synergistic effect of metformin and vemurufenib (PLX4032) as a molecular targeted therapy in anaplastic thyroid cancer: an in vitro study

Molecular Biology Reports - Survival rate of patients affected with anaplastic thyroid carcinoma (ATC) is less than 5% with current treatment. In ATC, BRAFV600E mutation is the major mutation that...     

Assessment of genetic variation among wild Alpinia nigra (Zingiberaceae) population: an approach based on molecular phylogeny

Molecular Biology Reports - Genetic structure was evaluated among wild Alpinia nigra (Gaertn.) B.L. Burtt, populations. The information of genetic relatedness was developed using random amplified...     

Transgenic plants as a source for the bioscavenging enzyme,human butyrylcholinesterase

Organophosphorous pesticides and nerve agents inhibit the enzyme acetylcholinesterase at neuronal synapses and in neuromuscular junctions. The resulting accumulation of acetylcholine overwhelms regulatory mechanisms, potentially leading to seizures and death from respiratory collapse. While current therapies are only capable of reducing mortality, elevation of the serum levels of the related enzyme butyrylcholinesterase (BChE) by application of the purified protein as a bioscavenger of organophosphorous compounds is effective in preventing all symptoms associated with poisoning by these toxins. However, BChE therapy requires large quantities of enzyme that can easily overwhelm current sources. Here, we report genetic optimization, cloning and high‐level expression of human BChE in plants. Plant‐derived BChE is shown to be biochemically similar to human plasma‐derived BChE in terms of catalytic activity and inhibitor binding. We further demonstrate the ability of the plant‐derived bioscavenger to protect animals against an organophosphorous pesticide challenge.     

Growth Suppression of Mouse Pituitary Corticotroph Tumor AtT20 Cells by Curcumin: A Model for Treating Cushing's Disease

Background

Pituitary corticotroph tumors secrete excess adrenocorticotrophic hormone (ACTH) resulting in Cushing''s disease (CD). Standard treatment includes surgery and, if not successful, radiotherapy, both of which have undesirable side effects and frequent recurrence of the tumor. Pharmacotherapy using PPARγ agonists, dopamine receptor agonists, retinoic acid or somatostatin analogs is still experimental. Curcumin, a commonly used food additive in South Asian cooking, has potent growth inhibitory effects on cell proliferation. Our laboratory recently demonstrated that curcumin inhibited growth and induced apoptosis in prolactin- and growth hormone-producing tumor cells [1]. Subsequently, Schaaf et.al. confirmed our findings and also showed the in vivo effectiveness of curcumin to suppress pituitary tumorigenesis. However the molecular mechanism that mediate this effect of curcumin are still unknown.

Principal Findings

Using the mouse corticotroph tumor cells, AtT20 cells, we report that curcumin had a robust, irreversible inhibitory effect on cell proliferation and clonogenic property. The curcumin-induced growth inhibition was accompanied by decreased NFκB activity. Further, curcumin down-regulated the pro-survival protein Bcl-xL, depolarized the mitochondrial membrane, increased PARP cleavage, which led to apoptotic cell death. Finally, curcumin had a concentration-dependent suppressive effect on ACTH secretion from AtT20 cells.

Conclusion

The ability of curcumin to inhibit NFκB and induce apoptosis in pituitary corticotroph tumor cells leads us to propose developing it as a novel therapeutic agent for the treatment of CD.     

Akt/Protein kinase B modulates macrophage inflammatory response to Francisella infection and confers a survival advantage in mice

The Gram-negative bacterium Francisella novicida infects primarily monocytes/macrophages and is highly virulent in mice. Macrophages respond by producing inflammatory cytokines that confer immunity against the infection. However, the molecular details of host cell response to Francisella infection are poorly understood. In this study, we demonstrate that F. novicida infection of murine macrophages induces the activation of Akt. Inhibition of Akt significantly decreases proinflammatory cytokine production in infected macrophages, whereas production of the anti-inflammatory cytokine IL-10 is enhanced. Analysis of the mechanism of Akt influence on cytokine response demonstrated that Akt promotes NF-kappaB activation. We have extended these findings to show that Akt activation may be regulated by bacterial genes associated with phagosomal escape. Infection with mglA mutants of F. novicida elicited sustained activation of Akt in comparison to cells infected with wild-type F. novicida. Concomitantly, there was significantly higher proinflammatory cytokine production and lower IL-10 production in cells infected with the mglA mutant. Finally, transgenic animals expressing constitutively active Akt displayed a survival advantage over their wild-type littermates when challenged with lethal doses of F. novicida. Together, these observations indicate that Akt promotes proinflammatory cytokine production by F. novicida-infected macrophages through its influence on NF-kappaB, thereby contributing to immunity against F. novicida infection.     

DNA-binding studies of mixed-ligand (ethylenediamine)ruthenium(II) complexes

A series of mixed-ligand ruthenium(II) complexes of the type [Ru(en)(2)bpy](2+) (bpy=2,2-bipyridine; 1), [Ru(en)(2)phen](2+) (phen=1,10-phenantroline; 2), [Ru(en)(2)IP](2+) (IP=imidazo[4,5-f][1,10]phenanthroline; 3), and [Ru(en)(2)PIP](2+) (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline; 4) have been isolated and characterized by UV/VIS, IR, and (1)H-NMR spectral methods. The binding of the complexes with calf thymus DNA has been investigated by absorption, emission spectroscopy, viscosity measurements, DNA melting, and DNA photo-cleavage. The spectroscopic studies together with viscosity measurements and DNA melting studies support that complexes 1 and 2 bind to CT DNA (=calf thymus DNA) by groove mode. Complex 2 binds more avidly to CT DNA than complex 1, complexes 3 and 4 bind to CT DNA by intercalation mode, 4 binds more avidly to CT DNA than 3. Noticeably, the four complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA.