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Pre-Natal Epigenetic Influences on Acute and Chronic Diseases Later in Life, such as Cancer: Global Health Crises Resulting from a Collision of Biological and Cultural Evolution

  • Trosko, James E.
    • Preventive Nutrition and Food Science
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    • v.16 no.4
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    • pp.394-407
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    • 2011
  • Better understanding of the complex factors leading to human diseases will be necessary for both long term prevention and for managing short and long-term health problems. The underlying causes, leading to a global health crisis in both acute and chronic diseases, include finite global health care resources for sustained healthy human survival, the population explosion, increased environmental pollution, decreased clean air, water, food distribution, diminishing opportunities for human self-esteem, increased median life span, and the interconnection of infectious and chronic diseases. The transition of our pre-human nutritional requirements for survival to our current culturally-shaped diet has created a biologically-mismatched human dietary experience. While individual genetic, gender, and developmental stage factors contribute to human diseases, various environmental and culturally-determined factors are now contributing to both acute and chronic diseases. The transition from the hunter-gatherer to an agricultural-dependent human being has brought about a global crisis in human health. Initially, early humans ate seasonally-dependent and calorically-restricted foods, during the day, in a "feast or famine" manner. Today, modern humans eat diets of caloric abundance, at all times of the day, with foods of all seasons and from all parts of the world, that have been processed and which have been contaminated by all kinds of factors. No longer can one view, as distinct, infectious agent-related human acute diseases from chronic diseases. Moreover, while dietary and environmental chemicals could, in principle, cause disease pathogenesis by mutagenic and cytotoxic mechanisms, the primary cause is via "epigenetic", or altered gene expression, modifications in the three types of cells (e.g., adult stem; progenitor and terminally-differentiated cells of each organ) during all stages of human development. Even more significantly, alteration in the quantity of adult stem cells during early development by epigenetic chemicals could either increase or decrease the risk to various stem cell-based diseases, such as cancer, later in life. A new concept, the Barker hypothesis, has emerged that indicates pre-natal maternal dietary exposures can now affect diseases later in life. Examples from the studies of the atomic bomb survivors should illustrate this insight.

Hepatic Resection for Hepatic Metastases from Gastric Adenocarcinoma

  • Baek, Hyoung-Un;Kim, Sang Bum;Cho, Eung-Ho;Jin, Sung-Ho;Yu, Hang Jong;Lee, Jong-Inn;Bang, Ho-Yoon;Lim, Chang-Sup
    • Journal of Gastric Cancer
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    • v.13 no.2
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    • pp.86-92
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    • 2013
  • Purpose: The effects of hepatic resection on patients with metastatic tumors from gastric adenocarcinomas are unclear. Therefore, we analyzed early clinical outcomes in patients who underwent surgical resection for hepatic metastases from gastric adenocarcinomas. Materials and Methods: From January 2003 to December 2010, 1,508 patients with primary gastric cancers underwent curative gastric resections at the Korea Cancer Center Hospital. Of these patients, 12 with liver-only metastases underwent curative hepatic resection. Their clinical data were analyzed retrospectively. Results: The median follow-up period was 12.5 months (range, 1~85 months); no operative mortalities or major complications were observed. Three patients underwent synchronous resections, and 9 underwent metachronous resections. In the latter group, the median interval between gastrectomy and hepatectomy for hepatic metastasis was 10.5 months (range, 5~47 months). The overall 1- and 5-year survival rates of these 12 patients were 65% and 39%, respectively, with a median overall survival of 31.0 months; 2 patients survived for >5 years. Conclusions: Hepatic resection can be a feasible procedure for treating hepatic metastases from gastric adenocarcinomas. Although this study was small and involved only selected cases, the outcomes of the hepatic resections were comparable and long-term (>5 years) survivors were identified. Surgical resection of the liver can be considered a feasible option in managing hepatic metastases from gastric adenocarcinomas.

Characteristics of Initiation and Termination of Tibialis Anterior Contraction in Adults With Hemiplegia: A Preliminary Study

  • Chung, Yi-Jung;Lee, Jung-Ah;Shin, Won-Seob;An, Seung-Heon;Lee, Eun-Woo;Jung, Kyoung-Sim
    • Physical Therapy Korea
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    • v.14 no.4
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    • pp.50-57
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    • 2007
  • The purpose of this study was to investigate the relationship between delays in initiation and termination of tibialis anterior contraction through surface electromyographic (sEMG) analysis in adults with hemiplegia and healthy subjects and clinical assessment of lower-limb mobility. EMG activity of 6 long-term survivors of stroke and 5 healthy subjects was recorded during maximal isometric ankle dorsiflexion in 3 seconds beeper signals. It must be done as fast and forcefully as possible. Lower limb mobility was assessed with Modified Emory Functional Ambulation Profile (mEFAP). Delay in initiation and termination of muscle contraction was significantly prolonged in the affected lower limb relative to the unaffected limb. Termination of muscle contraction in the hemiplegic lower limb was significantly delayed than the initiation on the affected sides. Delay in initiation and termination of muscle contraction correlated significantly with a few range of mEFAP. Abnormally delayed initiation and termination of muscle contraction may contribute to hemiparetic lower limb mobility in hemiparetic patients. Consequently, this study showed that abnormal delay of initiation and termination of muscle contraction may contribute to hemiparetic lower limb mobility in adults with hemiplegia. Further studies are needed to demonstrate a treatment effect.

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Neural Substrates of Posttraumatic Stress Disorder : Functional Magnetic Resonance Imaging Study Using Negative Priming Task (외상 후 스트레스 장애의 신경기반 : 부적점화과제와 기능자기공명영상 연구)

  • Lee, Byeong-Taek;Ryu, Jeong;Lee, Dong Hoon;Sohn, Myeong-Ho;Kang, Nae Hee;Ham, Byung-Joo;Choi, Nam Hee
    • Korean Journal of Biological Psychiatry
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    • v.15 no.2
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    • pp.110-117
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    • 2008
  • Objectives : Posttraumatic stress disorder(PTSD) has been primarily associated with emotional problems. Recently, however, the impact of PTSD on cognitive processes has interested a growing number of researchers. The current study is aimed at investigating the cognitive aspects of PTSD at both behavioral and neurological levels. Methods : We recruited individuals with PTSD who survived the Daegu subway explosion in 2003 as well as non-PTSD individuals as a control group. To evaluate the inhibitory processes and the neural mechanisms, we had these individuals perform the negative priming task simultaneously with functional MRI scanning. Results : Behaviorally, the negative priming effect was intact in the control group but was not evident in the PTSD group. In the imaging results, only the PTSD group showed the negative priming effect (i.e., increased activation of the negative priming condition as opposed to the neutral condition) in the dorsolateral prefrontal cortex, anterior cingulate cortex, and inferior temporal gyrus. The PTSD group also showed increased activity for the positive priming condition as opposed to the neutral condition in the claustrum. These results confirm and extend the previous findings that the integrity of the ACC is compromised in the trauma survivors due to disrupted white matter tract. Conclusions : The current results suggest that deteriorated performance of the PTSD group may be due to the functional problem as well as the structural abnormalities.

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Inhibition of Fat-Storing Cell Proliferation by a Monomeric Arginase Derived from Perfused Rat Liver

  • Kim, Ki-Yong;Choi, In-Pyo;Kim, Soung-Soo
    • BMB Reports
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    • v.33 no.3
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    • pp.213-220
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    • 2000
  • A fulminant hepatitis is associated with massive liver cell necrosis and a high mortality rate. But survivors regenerate a normal liver and do not have chronic liver disease. This clinical course suggests that the acutely injured livers release a factor that allows a recovery from chronic hepatitis or cirrhosis. The objective of this study was to isolate and characterize an anti-fibrotic factor from acutely damaged rat livers. The liver cell necrosis was prepared from rat by warm ischemical perfusion and the perfusates were assessed against the growth inhibition of fat-storing cells (FSC). A liver-derived growth inhibitory factor (LDGIF) was purified from ischemically damaged rat livers by chromatographies on Sephacryl S-300, CM Sepharose, hydroxyapatite, and Superose 12. The LDGIF was isolated with an overall purification of 194-fold and 40% recovery. Although LDGIF was identified as the rat liver arginase by Nterminal sequence analysis, LDGIF exists as a monomer and the purified native arginase has a trimer form. Furthermore, LDGIF has a lower enzyme activity on the hydrolysis of L-arginine and a higher inhibitory effect on proliferation of FSC than the normal rat liver arginase. The catalytic activity of LDGIF is ascribed to the monomeric characteristics of the LDGIF. Therefore, the inhibitory action of LDGIF might not be due to the arginine depletion by the catalytic activity of arginase. In conclusion, the presence of the LDGIF could interpret the clinical course that serious fibrosis is not found in the liver of patients recovering from severe hepatic necrosis due to fulminant hepatitis, suggesting that this LDGIF may provide a novel target for the prevention and treatment of hepatic fibrosis.

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Thyroid dysfunction in very low birth weight preterm infants

  • Lee, Ji Hoon;Kim, Sung Woo;Jeon, Ga Won;Sin, Jong Beom
    • Clinical and Experimental Pediatrics
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    • v.58 no.6
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    • pp.224-229
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    • 2015
  • Purpose: Thyroid dysfunction is common in preterm infants. Congenital hypothyroidism causes neurodevelopmental impairment, which is preventable if properly treated. This study was conducted to describe the characteristics of thyroid dysfunction in very low birth weight infants (VLBWIs), evaluate risk factors of hypothyroidism, and suggest the reassessment of thyroid function with an initially normal thyroid-stimulating hormone (TSH) as part of a newborn screening test. Methods: VLBWIs (January 2010 to December 2012) were divided into two groups according to dysfunction-specific thyroid hormone replacement therapy, and associated factors were evaluated. Results: Of VLBWIs, 246 survivors were enrolled. Only 12.2% (30/246) of enrolled subjects exhibited thyroid dysfunction requiring thyroid hormone replacement. Moreover, only one out of 30 subjects who required thyroid hormone treatment had abnormal thyroid function in the newborn screening test with measured TSH. Most of the subjects in the treatment group (22/30) exhibited delayed TSH elevation. Gestational age, Apgar score, antenatal steroids therapy, respiratory distress syndrome, patent ductus arteriosus, sepsis, intraventricular hemorrhage, postnatal steroids therapy, and duration of mechanical ventilation did not differ between the two groups. Birth weight was smaller and infants with small for gestational age were more frequent in the treatment group. Conclusion: Physicians should not rule out suggested hypothyroidism, even when thyroid function of a newborn screening test is normal. We suggest retesting TSH and free thyroxine in high risk preterm infants with an initially normal TSH level using a newborn screening test.

Outcomes of Extremely Low Birth Weight Infants at the Asan Medical Center between 2003 and 2006 (단일 기관에서의 초극소 저출생 체중아의 치료 성적(2003-2006))

  • Park, Mee-Rim;Lee, Byong-Sop;Kim, Ellen A.;Kim, Ki-Soo;Pi, Soo-Young
    • Neonatal Medicine
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    • v.15 no.2
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    • pp.123-133
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    • 2008
  • Purpose: The purpose of this study was to determine the outcomes of extremely low birth weight infants (ELBWI) who were born at the Asan Medical Center and evaluate the recent status of neonatal intensive care and associated problems. Methods:We retrospectively evaluated 120 inborn ELBWI who were admitted to the NICU of the Asan Medical Center between 2003 and 2006. The survival rate, neurodevelopmental outcomes, maternal and infant factors, and infant mordibities were evaluated and the relationships with survival and catch-up growth were investigated. Results:The survival rate of the ELBWI was 82% at a mean gestational age of 27+2 weeks, and with a mean birth weight of 801.3${\pm}$129.0 g. The duration of hospitalization was 85.7${\pm}$27.2 days, the duration of O2 use was 43.9${\pm}$35.4 days, and the duration of ventilatory support was 20.9${\pm}$20.9 days among the survivors. The incidence of respiratory distress syndrome, chronic lung disease, severe intraventricular hemorrhage, and periventricular leukomalacia were 41.8%, 61.2%, 3%, and 4%, respectively. The mean mental developmental index and psychomotor development index of Bailey Scales of Infant Development (II) at follow-up were 83.4${\pm}$18.2 and 83.3${\pm}$20.3, respectively. Among the infants who had >18 months of follow-up, 50.8% had catch-up growth at 12 months. Conclusion:The survival rate of ELBWI has improved; however, the morbidities remain high, thus indicating further efforts must be implemented to reduce morbidity and improve neurodevelopmental outcomes.

In silico docking of methyl isocyanate (MIC) and its hydrolytic product (1, 3-dimethylurea) shows significant interaction with DNA Methyltransferase 1 suggests cancer risk in Bhopal-Gas-Tragedy survivors

  • Khan, Inbesat;Senthilkumar, Chinnu Sugavanam;Upadhyay, Nisha;Singh, Hemant;Sachdeva, Meenu;Jatawa, Suresh Kumar;Tiwari, Archana
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7663-7670
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    • 2015
  • DNA methyltransferase 1 (DNMT1) is a relatively large protein family responsible for maintenance of normal methylation, cell growth and survival in mammals. Toxic industrial chemical exposure associated methylation misregulation has been shown to have epigenetic influence. Such misregulation could effectively contribute to cancer development and progression. Methyl isocyanate (MIC) is a noxious industrial chemical used extensively in the production of carbamate pesticides. We here applied an in silico molecular docking approach to study the interaction of MIC with diverse domains of DNMT1, to predict cancer risk in the Bhopal population exposed to MIC during 1984. For the first time, we investigated the interaction of MIC and its hydrolytic product (1,3-dimethylurea) with DNMT1 interacting (such as DMAP1, RFTS, and CXXC) and catalytic (SAM, SAH, and Sinefungin) domains using computer simulations. The results of the present study showed a potential interaction of MIC and 1,3-dimethylurea with these domains. Obviously, strong binding of MIC with DNMT1 interrupting normal methylation will lead to epigenetic alterations in the exposed humans. We suggest therefore that the MIC-exposed individuals surviving after 1984 disaster have excess risk of cancer, which can be attributed to alterations in their epigenome. Our findings will help in better understanding the underlying epigenetic mechanisms in humans exposed to MIC.

Differences in Prognostic Factors between Early and Late Recurrence Breast Cancers

  • Payandeh, Mehrdad;Sadeghi, Masoud;Sadeghi, Edris
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6575-6579
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    • 2015
  • Background: Breast cancer (BC) is the most frequent malignancy among females and is a leading cause of death of middle-aged women. Herein, we evaluated baseline characteristics for BC patients and also compared these variables across ealry and late recurrence groups. Materials and Methods: Between 1995 to 2014, among female breast cancer patients referred to our oncology clinic, eighty-six were entered into our study. All had distant metastasis. Early recurrence was defined as initial recurrence within 5 years following curative surgery irrespective of site. Likewise, late recurrence was defined as initial recurrence after 5 years. No recurrence was defined for survivors to a complete minimum of 10 years follow-up. Significant prognostic factors associated with early or late recurrence were selected according to the Akaike Information Criterion. Results: The median follow-up was 9 years (range, 1-18 years). During follow-up period, 51 recurrences occurred (distant metastasis), 31 early and 20 late. According to the site of recurrence, there were 51 distant. In this follow-up period, 19 patients died. Compared with the early recurrence group, the no recurrence group had lower lymph node involvement and more p53 positive lesions but the late recurrence group had lower tumor size. In comparison to no recurrence, p53 (odds ratio [OR] 6.94, 95% CI 1.49-32.16) was a significant prognostic factor for early recurrence within 5 years. Conclusions: Tumor size, p53 and LN metastasis are the most important risk factors for distance recurrence especially in early recurrence and also between of them, p53 is significant prognostic factor for early recurrence.

Lack of Influence of Pregnancy on the Prognosis of Survivors of Thyroid Cancer

  • Budak, Adnan;Gulhan, Ibrahim;Aldemir, Onur Suleyman;Ileri, Alper;Tekin, Emine;Ozeren, Mehmet
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6941-6943
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    • 2013
  • Objective: The aim of this study is to investigate the influence of pregnancy on prognosis of thyroid cancer. Methods: A total of 72 patients aged between 15-45 years who underwent total or subtotal thyroidectomy and subsequently radioablation were followed up under suppression. Individuals who had term pregnancies after diagnosis of cancer (group 1, n: 36) and who were non-pregnant (group 2, n:36) were included in the study. Both groups were compared in terms of scintigraphic relapse and metastasis, ultrasonographic relapse, stage change of lympadenopathy at the beginning and at the end of the study. Results: Relapse was detected in 4 out of 36 pregnant patients (11.1%) and in 5 out of 36 non-pregnant patients (13.9%) with no significant difference between groups (p=1.00). Pathologic lymphadenopathy was detected in 2 out of 36 pregnant patients (5.6%) and in 2 out of 36 non-pregnant patients (5.6%) (p=1.00), and metastasis in 3 (8.3%) and in 1 (2.8%), respectively (p=0.61). While stage change was detected in only one pregnant patient (2.8%), and none of the non-pregnant again there was no significant difference (p=1.00). Conclusions: We conclude that pregnancy does not have an influence on prognosis of thyroid cancer.