003.01. National Laboratory Astana
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Item Open Access Thyroid abnormality trend over time in Northeastern Regions of Kazakstan, adjacent to the Semipalatinsk Nuclear Test Site: a case review of pathological findings for 7271 patients(Journal of Radiation Research, 2000) Zhumadilov, Zhaxybay; GUSEV, BORIS I.; TAKADA, JUN; HOSHI, Masaharu; Kimura, AKIRO; Hayakawa, Norihiko; Takeichi, NobuoFrom 1949 through 1989 nuclear weapons testing carried out by the former Soviet Union at the Semipalatinsk Nuclear Test Site (SNTS) resulted in local fallout affecting the residents of Semipalatinsk, Ust-Kamenogorsk and Pavlodar regions of Kazakstan. To investigate the possible relationship between radiation exposure and thyroid gland abnormalities, we conducted a case review of pathological findings of 7271 urban and rural patients who underwent surgery from 1966–96. Of the 7271 patients, 761 (10.5%) were men, and 6510 (89.5%) were women...Item Open Access Tooth enamel EPR dosimetry: optimization of EPR spectra recording parameters and effect of sample mass on spectral sensitivity(Journal of Radiation Research. http://jrr.jstage.jst.go.jp, 2005) Zhumadilov, Kassym; Ivannikov, Alexander; Skvortsov, Valeriy; Stepanenko, Valeriy; Zhumadilov, Zhaxybay; Endo, Satoru; Tanaka, Kenichi; Hoshi, Masaharuconditions were optimized. The uncertainty of dose determination was obtained as the mean square deviation of doses, determined with the use of a spectra deconvolution program, from the nominal doses for ten enamel samples irradiated in the range from 0 to 500 mGy. The spectra were recorded at different microwave powers and accumulation times. It was shown that minimal uncertainty is achieved at the microwave power of about 2 mW for a used spectrometer JEOL JES-FA100. It was found that a limit of the accumulation time exists beyond which uncertainty reduction is ineffective. At an established total time of measurement, reduced uncertainty is obtained by averaging the experimental doses determined from recorded spectra following intermittent sample shaking and sample tube rotation, rather than from one spectrum recorded at longer accumulation time. The effect of sample mass on the spectrometer’s sensitivity was investigated in order to find out how to make appropriate corrections.Item Open Access Around Semipalatinsk nuclear test site: progress of dose estimations relevant to the consequences of nuclear tests(J. Radiat. Res. Vol. 47, Suppl. A (2006); http://jrr.jstage.jst.go.jp, 2005-03-09) Stepanenko, Valeriy F.The paper is an analytical overview of the main results presented at the 3 rd Dosimetry Workshop in Hiroshima (9–11 of March 2005), where different aspects of the dose reconstruction around the Semipalatinsk nuclear test site (SNTS) were discussed and summarized.Item Open Access Nuclear abnormalities in aspirated thyroid cells and chromosome aberrations in lymphocytes of residents near the Semipalatinsk Nuclear Test Site(Journal of Radiation Research. http://jrr.jstage.jst.go.jp, 2006) Takeichi, Nobuo; Hoshi, Masaharu; Iida, Shozo; Tanaka, Kimio; Harada, Yuka; Zhumadilov, Zhaxybay; Chaizhunusova, Nailya; Apsalikov, Kazbek N.; Noso, Yoshihiro; Inaba, Toshiya; Tanaka, Kenichi; Endo, SatoruChromosomal studies in peripheral lymphocytes from 63 residents near the Semipalatinsk nuclear test site, at ages of 52–63 years old, were performed in 2001–2002. A higher rate of chromosome aberrations was observed in the two contaminated villages, Dolon and Sarjal, compared with the control village, Kokpekti. Moreover, a relationship of frequency of cells with radiation induced chromosome aberrations and the previously estimated exposure dose was observed. Furthermore, apparent nuclear abnormalities (ANA) of thyroid follicular cells were studied in 30 out of 63 residents, who were examined for chromosome aberrations. A higher rate of ANA was also found in the residents in the exposed villages compared with those in the control village. These results suggest radiation effects both on the chromosomes in peripheral lymphocytes and on the follicular cells in the thyroid.Item Open Access Comparison of the characteristic features of bonghan ducts, blood and lymphatic capillaries(Journal of Acupuncture and Meridian Studies, 2009-03-31) Ogay, Vyacheslav; Bae, Kyung Hee; Kim, Ki Woo; Soh, Kwang-supObjective: To show that the characteristic morphological and ultrastructural features of a Bonghan corpuscle and duct presented here are consistent with the description given in the early reports of Bonghan Kim. Materials and Methods: We compared the morphological aspects of Bonghan ducts with those of blood and lymphatic capillaries on the ultrastructural level to display the manifestly distinctive nature of the Bonghan system. Results: The walls of the ductules were observed to be composed of a single layer of endothelial cells with characteristic rod-shaped nuclei and were not surrounded by a basal lamina or by accessory cells, such as pericytes or smooth muscle cells. The abluminal cell membranes of Bonghan ductules were not attached by anchoring filaments to the fibers of extracellular matrices as observed in lymphatic capillaries.Item Open Access Bonghan Ducts as Possible Pathways for Cancer Metastasis(Journal of Acupuncture and Meridian Studies, 2009-04-01) Yoo, Jung Sun; Kim, Hong Bae; Ogay, Vyacheslav; Lee, Byung-Cheon; Ahn, Saeyoung; Soh, Kwang-supObjective: The present study has been designed to find a possible new route for the metastasis of cancer cells on the fascia surrounding tumor tissue using a novel technique of trypan blue staining. Materials and Methods: Tumor tissues were grown in the skin of nude mice after subcutaneous inoculation with human lung cancer cells. Trypan blue was recently identified as a dye with specificity for Bonghan ducts (BHDs) and not other tissues, such as blood or lymph vessels or nerves. Results: We demonstrate that the trypan blue staining technique allows the first visualization of BHDs which are connected to tumor tissues.Item Open Access Visualization of Bonghan Microcells by Electron and Atomic Force Microscopy(Journal of Acupuncture and Meridian Studies, 2009-04-13) Baik, Ku Youn; Ogay, Vyacheslav; Jeoung, Sae Chae; Soh, Kwang-supObjectives: The origin of adult stem cells remains an open question. If they derive from embryos, it is difficult to determine the mechanism which interrupts their differentiation during tissue formation. In the 1960s, the Bonghan microcell was suggested as one possible, yet to be described, route of stem cell production, such that they have the potential to proliferate to produce normal cells. Materials and Methods: In this study, Bonghan microcells were isolated from Bonghan tissues on rat organ surfaces, and their detailed morphology examined by electron and atomic force microscopy. Results: The ultrastructure observed distinguished them from apoptotic bodies and other microorganisms, and their unique, possible proliferation feature, as protruding threads, was imaged by atomic force microscopy.Item Open Access Синтез, строение и свойства гидразидов β-аминопропановой кислоты и их производных(КазНУ им. аль-Фараби, 2010) Berillo (Берилло), Dmitriy (Дмитрий)Настоящая работа посвящена комплексному исследованию в области синтеза потенциально биологически активных веществ на основе гидразидов и нитрилов α-( и β-)-аминопропановых кислот, установлению закономерностей их гетероциклизации и изучению биологической активности новых производных гидразидов и нитрилов α-( и β-)- аминокислот.Item Open Access Membrane biophysics and mechanics in Alzheimer's disease(Mol Neurobiol, 2010-05-01) Yang, Xiaoguang; Askarova, Sholpan; Lee, James C-M.Alzheimer's disease is a chronic neurodegenerative disorder characterized by neuronal loss, cerebrovascular inflammation, and accumulation of senile plaques in the brain parenchyma and cerebral blood vessels. Amyloid-β peptide (Aβ), a major component of senile plaques, has been shown to exert multiple toxic effects to neurons, astrocytes, glial cells, and brain endothelium. Oligomeric Aβ can disturb the structure and function of cell membranes and alter membrane mechanical properties, such as membrane fluidity and molecular order. Much of these effects are attributed to their capability to trigger oxidative stress and inflammation. In this review, we discuss the effects of Aβ on neuronal cells, astrocytes, and cerebral endothelial cells with special emphasis on cell membrane properties and cell functions.Item Open Access Low energy laser light (632.8 nm) suppresses amyloid-β peptide-induced oxidative and inflammatory responses in astrocytes(US National Library of Medicine National Institutes of Health, 2010-09-25) Yang, Xiaoguang; Askarova, Sholpan; Sheng, Wenwen; Chen, JK; Sun, Albert Y.; Sun, Grace Y.; Yao, Gang; Leea, James C-M.Oxidative stress and inflammation are important processes in the progression of Alzheimer's disease (AD). Recent studies have implicated the role of amyloid β-peptides (Aβ) in mediating these processes. In astrocytes, oligomeric Aβ induces the assembly of NADPH oxidase complexes resulting in its activation to produce anionic superoxide. Aβ also promotes production of pro-inflammatory factors in astrocytes. Since low energy laser has previously been reported to attenuate oxidative stress and inflammation in biological systems, the objective of this study was to examine whether this type of laser light was able to abrogate the oxidative and inflammatory responses induced by Aβ. Primary rat astrocytes were exposed to Helium-Neon laser (λ=632.8 nm), followed by the treatment with oligomeric Aβ. Primary rat astrocytes were used to measure Aβ-induced production of superoxide anions using fluorescence microscopy of dihydroethidium (DHE), assembly of NADPH oxidase subunits by the colocalization between the cytosolic p47phox subunit and the membrane gp91phox subunit using fluorescent confocal microscopy, phosphorylation of cytosolic phospholipase A2 (cPLA2), and expressions of pro-inflammatory factors including interleukin-1β (IL-1β) and inducible nitric-oxide synthase (iNOS) using Western blot Analysis. Our data showed that laser light at 632.8 nm suppressed Aβ-induced superoxide production, colocalization between NADPH oxidase gp91phox and p47phox subunits, phosphorylation of cPLA2, and the expressions of IL-1β and iNOS in primary astrocytes. We demonstrated for the first time that 632.8 nm laser was capable of suppressing cellular pathways of oxidative stress and inflammatory responses critical in the pathogenesis in AD. This study should prove to provide the groundwork for further investigations for the potential use of laser therapy as a treatment for AD.Item Open Access Electrical сharacterization of proposed transpositional acupoints on the Urinary Bladder Meridian in a Rat Model(Hindawi Publishing Corporation. Evidence-Based Complementary and Alternative Medicine., 2011) Han, Hyun-Jung; Park, Sang-Jun; Soh, Kwang-sup; Myoung, Hyoun-Seok; Lee, Kyoung-Joung; Ogay, Vyacheslav; Lee, Yong-HeumSpecific electrical characteristicsof acupointswere investigated on the urinary bladder (BL) meridian in 14 rats. BL acupointsand non-acupoints on the back were selected and their electrical voltages were measured by using aSPACsystem.The mean voltages of each point or each line were statistically analyzed by using the ANOVA test...Item Open Access Impacts of membrane biophysics in Alzheimer’s disease: from amyloid precursor protein processing to Aβ peptide-induced membrane changes(SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease, 2011-01-21) Askarova, Sholpan; Yang, Xiaoguang; Lee, James C-M.An increasing amount of evidence supports the notion that cytotoxic effects of amyloid-β peptide (Aβ), the main constituent of senile plaques in Alzheimer’s disease (AD), are strongly associated with its ability to interact with membranes of neurons and other cerebral cells. Aβ is derived from amyloidogenic cleavage of amyloid precursor protein (AβPP) by β- and γ-secretase. In the nonamyloidogenic pathway, AβPP is cleaved by α-secretases. These two pathways compete with each other, and enhancing the non-amyloidogenic pathway has been suggested as a potential pharmacological approach for the treatment of AD. Since AβPP, α-, β-, and γ-secretases are membrane-associated proteins, AβPP processing and Aβ production can be affected by the membrane composition and properties. There is evidence that membrane composition and properties, in turn, play a critical role in Aβ cytotoxicity associated with its conformational changes and aggregation into oligomers and fibrils. Understanding themechanisms leading to changes in a membrane’s biophysical properties and how they affect AβPP processing and Aβ toxicity should prove to provide new therapeutic strategies for prevention and treatment of AD.Item Open Access Behavior and food consumption pattern of the population exposed in 1949–1962 to fallout from Semipalatinsk nuclear test site in Kazakhstan(Radiation and Environmental Biophysics, 2011-03) Drozdovitch, Vladimir; Schonfeld, Sara; Akimzhanov, Kuat; Aldyngurov, Daulet; Land, Charles E.; Luckyanov, Nickolas; Mabuchi, Kiyohiko; Potischman, Nancy; J. Schwerin, Michael J.; Semenova, Yulia; Tokaeva, Alma; Zhumadilov, Zhaxybay; Bouville, André; Simon, Steven L.The relationship between radiation exposure from nuclear weapons testing fallout and thyroid disease in a group of 2,994 subjects has been the subject of study by the US National Cancer Institute. In that study, radiation doses to the thyroid were estimated for residents of villages in Kazakhstan possibly exposed to deposition of radioactive fallout from nuclear testing conducted by the Soviet Union at the Semipalatinsk Nuclear Test Site in Kazakhstan between 1949 and 1962. The study subjects included individuals of both Kazakh and Russian origin who were exposed during childhood and adolescence. An initial dose reconstruction used for the risk analysis of Land et al. (Radiat Res 169:373-383, 2008) was based on individual information collected from basic questionnaires administered to the study population in 1998. However, because data on several key questions for accurately estimating doses were not obtained from the 1998 questionnaires, it was decided to conduct a second data collection campaign in 2007. Due to the many years elapsed since exposure, a well-developed strategy was necessary to encourage accurate memory recall.Item Open Access Effects of amyloid beta peptide on neurovascular cells(Central Asian Journal of Global Health, 2012) Askarova, Sholpan; Tsoy, Andrey; Shalakhmetova, Tamara; Lee, James C-M.Alzheimer’s disease (AD) is a chronic neurodegenerative disorder, which is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in specific regions of the brain, accompanied by impairment of the neurons, and progressive deterioration of cognition and memory of affected individuals. Although the cause and progression of AD are still not well understood, the amyloid hypothesis is dominant and widely accepted. According to this hypothesis, an increased deposition of amyloid-β peptide (Aβ) in the brain is the main cause of the AD’s onset and progression. There is increasing body of evidence that blood-brain barrier (BBB) dysfunction plays an important role in the development of AD, and may even precede neuron degeneration in AD brain. In the early stage of AD, microvasculature deficiencies, inflammatory reactions, surrounding the cerebral vasculature and endothelial dysfunctions are commonly observed. Continuous neurovascular degeneration and accumulation of Aβ on blood vessels resulting in cerebral amyloid angiopathy is associated with further progression of the disease and cognitive decline. However, little is known about molecular mechanisms that underlie Aβ induced damage of neurovascular cells. In this regards, this review is aimed to address how Aβ impacts the cerebral endothelium. Understanding the cellular pathways triggered by Aβ leading to alterations in cerebral endothelial cells structure and functions would provide insights into the mechanism of BBB dysfunction and inflammatory processes in Alzheimer’s, and may offer new approaches for prevention and treatment strategies for AD.Item Open Access Tuberculosis in Kazakhstan: analysis of risk determinants in national surveillance data(BMC Infectious Diseases. http://www.biomedcentral.com/1471-2334/12/262, 2012) Terlikbayeva, Assel; Hermosilla, Sabrina; Galea, Sandro; Schluger, Neil; Yegeubayeva, Saltanat; Abildayev, Tleukhan; Muminov, Talgat; Akiyanova, Farida; Bartkowiak, Laura; Zhumadilov, Zhaxybay; Sharman, Almaz; El-Bassel, NabilaDevelopment of tuberculosis (TB) is determined by various risk factors and the interactions of temporal and spatial distributions. The aim of this study was to identify the most salient risk factors for TB disease as well as multidrug resistant TB (MDR-TB) at the oblast (provincial) level in Kazakhstan.Item Open Access ZD7288 enhances long-term depression at early postnatal medial perforant path-granule cell synapses(Neural Plasticity, 2012-05-08) Guli, Xiati; Tokay, Tursonjan; Rohde, Marco; Bender, Roland A.; Kohling, Rudiger; Kirschstein, TimoHyperpolarization-activated, cyclic nucleotide-gated nonselective (HCN) channels modulate both membrane potential and resistance and play a significant role in synaptic plasticity. We compared the influence of HCN channels on long-term depression (LTD) at the medial perforant path-granule cell synapse in early postnatal (P9–15) and adult (P30–60) rats. LTD was elicited in P9–15 slices using low-frequency stimulation (LFS, 900 pulses, 1Hz; 80 ± 4% of baseline). Application of the specific HCN channel blocker ZD7288 (10 μM) before LFS significantly enhanced LTD (62 ± 4%; P < 0.01), showing HCN channels restrain LTD induction. However, when ZD7288 was applied after LFS, LTD was similar to control values and significantly different from the values obtained with ZD7288 application before LFS (81 ± 5%; P < 0.01), indicating that HCN channels do not modulate LTD expression. LTD in slices from adult rats were only marginally lower compared to those in P9–15 slices (85 ± 6%), but bath application of ZD7288 prior to LFS resulted in the same amount of LTD (85 ± 5%). HCN channels in adult tissue hence lose their modulatory effect. In conclusion, we found that HCN channels at the medial perforant path-granule cell synapse compromise LFS-associated induction, but not expression of LTD in early postnatal, but not in adult, rats.Item Open Access The role of infectious agents in urogenital cancers(BioMed Central, 2012-12-03) Alibek, Kenneth; Karatayeva, Nargis; Bekniyazov, IldarSince the late 1990s, infectious agents have been thought to play a role in the pathogenesis of approximately 15% of cancers. It is now widely accepted that infection of stomach tissue with the bacteria Helicobacter pylori is an important cause of stomach adenocarcinoma. In addition, oncogenic viruses, such as papilloma viruses, herpes viruses, and hepadnaviruses are strongly associated with increased risk of cervical cancer, lymphomas, liver cancer, amongst others. However, in the scientific community the percentage of cancers caused by pathogens is believed to be far higher than 15%. A significant volume of data collected to date show an association between infectious agents and urogenital cancers. These agents include Chlamydia trachomatis, Neisseria gonorrhoea, Mycoplasma genitalium and certain viruses that have been implicated in ovarian cancer.Item Open Access Role of Aβ-RAGE interaction in oxidative stress and cPLA2 activation in astrocytes and cerebral endothelial cells(Neuroscience. Author manuscript; available in PMC, 2012-12-29) Askarova, Sholpan; Yang, Xiaoguang; Sheng, Wenwen; Sun, Grace Y.; Lee, James C-M.Blood–brain barrier (BBB) dysfunctions have been implicated in the progression of Alzheimer's disease. Cerebral endothelial cells (CECs) and astrocytes are the main cell components of the BBB. Although amyloid-β oligomers (Aβ42) have been reported to mediate oxidative damage to the CECs and astrocytes and trigger the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, the cell surface binding site for Aβ42 and exact sequence of these events have yet to be elucidated. In this study, the receptor for advanced glycation endproducts (RAGE) was postulated to function as a signal transducing cell surface receptor for Aβ42 to induce reactive oxygen species (ROS) generation from NADPH oxidase and trigger downstream pathways for the phosphorylation of extracellular signal-regulated kinases (ERK1/2) and cytosolic phospholipase A2 (cPLA2). We found that Aβ42 competed with the anti-RAGE antibody (AbRAGE) to bind to RAGE on the surfaces of CECs and primary astrocytes. In addition, AbRAGE abrogate Aβ42-induced ROS production and the colocalization between the cytosolic (p47-phox) and membrane (gp91-phox) subunits of NADPH oxidase in both cell types. AbRAGE as well as NADPH oxidase inhibitor and ROS scavenger suppressed Aβ42-induced ERK1/2 and cPLA2 phosphorylation in CECs. At the same time, only AbRAGE, but neither NADPH oxidase inhibitor nor ROS scavenger, inhibited the ERK1/2 pathway and cPLA2 phosphorylation in primary astrocytes. Therefore, this study demonstrates that NADPH oxidase complex assembly and ROS production are not required for Aβ42 binding to RAGE at astrocytic surface leading to sequential phosphorylation of ERK1/2 and cPLA2, and suggests the presence of two different RAGE-dependent downstream pathways in the CECs and astrocytes.Item Open Access Перспективы применения системы экстракорпоральной респираторной поддержки в детской практике(Национальное общество регенеративной медицины, 2013) Мусин, Е.А.; Буланин, Д.С.; Жумадилов, Ж.Ш.; Олжаев, Ф.С.; Federspiel, W.; Jeffries, G.Оценка перспективы применения системы Hemolung в детской практике.Item Open Access Effect of Celergen, a marine derivative, on in vitro hepatocarcinogenesis(Drug Discoveries & Therapeutics. DOI: 10.5582/ddt.2013.v7.5.196, 2013) Catanzaro, R.; Zerbinati, N.; Solimene, U.; Celep, G.; Marotta, F.; Kushugulova, A.; Milazzo, M.; Tomella, C.; Bertuccelli, G.; Zhumadilov, Z.The aim of this study was to test for a potential anticarcinogenic effect of Celergen, a marine derivative devoid of traceable amounts of inorganic arsenic, on cell proliferation, cell cycle progression and apoptosis in the HepG2 human liver cancer cell line. Celergen significantly inhibited the proliferation of cancer cells in a dose-dependent manner while limiting the cell cycle progression at the G1 phase and significantly inducing apoptosis. Further examination showed that Celergen enhanced expression of the p21CIPl1WAF1, GADD153 genes and downregulated the c-myc gene. These results suggest that Celergen exerts promising chemopreventive properties to be further investigated.