The level and activity of critical regulatory proteins in cells are tightly controlled by several tiers of post-translational modifications. HIF-1α is maintained at low levels under normoxia conditions by the collaboration between PHD proteins and the VHL-containing E3 ubiquitin ligase complex. We recently identified a new physiologically relevant mechanism that regulates HIF-1α stability in the nucleus in response to cellular oxygen levels. This mechanism is based on the collaboration between the SET7/9 methyltransferase and the LSD1 demethylase. SET7/9 adds a methyl group to HIF-1α, which triggers degradation of the protein by the ubiquitin-proteasome system, whereas LSD1 removes the methyl group, leading to stabilization of HIF-1α under hypoxia conditions. In cells from knock-in mice with a mutation preventing HIF-1α methylation (Hif1αKA/KA), HIF-1α levels were increased in both normoxic and hypoxic conditions. Hif1αKA/KA knock-in mice displayed increased hematological parameters, such as red blood cell count and hemoglobin concentration. They also displayed pathological phenotypes; retinal and tumor-associated angiogenesis as well as tumor growth were increased in Hif1αKA/KA knock-in mice. Certain human cancer cells exhibit mutations that cause defects in HIF-1α methylation. In summary, this newly identified methylation-based regulation of HIF-1α stability constitutes another layer of regulation that is independent of previously identified mechanisms.
Sohn, Ki Cheul;Jung, Hyun-Jung;Lee, A-Jin;Kim, Sang-Gyung;Shin, ImHee;Kwak, Sang Gyu
The Journal of Korean Medicine
/
v.34
no.4
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pp.46-55
/
2013
Objectives: Classifying the pattern of jaundice during diagnosis will significantly improve the outcome of common KM interventions. This study aimed at determining an objective index for accurately diagnosing heat and dampness KM patterns in patients with jaundice. Methods: We systematically reviewed laboratory findings from case reports published in the scientific literature of Korean medicine. Cases were classified as following either the heat or dampness pattern. Biochemical indices were compared using a Bayesian factor (BF) analysis and standard t-tests. Results: The laboratory findings of 32 patients were evaluated. The heat pattern was observed in 17 patients and the dampness pattern in 15. No significant differences were observed between the 2 groups in terms of white blood cell count (BF=1.659); hemoglobin concentration (BF=2.627); platelet count (BF=1.019); or levels of direct bilirubin (BF=1.453), aspartate aminotransferase (BF=1.226), alanine aminotransferase (BF=1.340), alkaline phosphatase (BF=2.344), or gamma-glutamyl transpeptidase (BF=2.782). However, total bilirubin levels were significantly higher in the dampness pattern group (BF=0.854, P-value=0.070). Conclusions: Patients with high total bilirubin levels may predominantly follow the dampness pattern, while those with low levels may predominantly follow the heat pattern. These results are expected to be useful for the development of timely and efficient KM treatments as well as new integrative therapeutic approaches for jaundice. However, further studies are essential to fully validate the utility of total bilirubin as a biomarker for differentiating between heat and dampness patterns.
Objectives: This study compared the nutritional status of child-bearing age women between the Democratic People's Republic of Korea (North Korea) and the Republic of Korea (South Korea). Methods: The data presented in the DPRK Final Report of the National Nutrition Survey 2012 was utilized for the nutritional status and food intake of North Korean women. To produce the South Korean women's data comparable to those of North Korean women, the data from the 2012 National Health and Nutrition Survey were analyzed and the data presented in the 2010 Report of the Korean Agency for Technology and Standards were utilized. Results: The prevalence of maternal anemia (blood hemoglobin < 12.0 g/dL) was over 30% in all the age groups of North Korean women and 8.9%, 14.2%, 16.4% in 20-29, 30-39, 40-49 year old South Korean women, respectively. The prevalence of maternal protein-energy malnutrition (Mid-Upper Arm Circumference < 22.5 cm) was 25.2%, 21.4%, 21.8% in 20-29, 30-39, 40-49 year old North Korean women, respectively and less than 10% in all the age groups of South Korean women. Result of dietary diversity comparison showed that North Korean women consumed less food than South Korean women at all food groups: grains, fruits, vegetables, meat, and dairy. Percentage of North Korean women having consumed protein rich foods-meat and fish, eggs or dairy products-were much lower than those of South Korean women. Conclusions: The striking disparity of nutritional status between South and North Korean women indicates that nutrition support for North Korean women is essential in the process of preparation for a unified nation.
Purpose: This study investigated predictors of unresponsiveness to second-line intravenous immunoglobulin (IVIG) treatment for Kawasaki disease (KD). Methods: This was a single-center analysis of the medical records of 588 patients with KD who had been admitted to Asan Medical Center between 2006 and 2014. Related clinical and laboratory data were analyzed by univariate and multivariate logistic regression analyses. Results: Eighty (13.6%) of the 588 patients with KD were unresponsive to the initial IVIG treatment and received a second dose. For these 80 patients, univariate analysis of the laboratory results obtained before administering the second-line IVIG treatment showed that white blood cell count, neutrophil percent, hemoglobin level, platelet count, serum protein level, albumin level, potassium level, and C-reactive protein level were significant predictors. The addition of methyl prednisolone to the second-line regimen was not associated with treatment response (odds ratio [OR], 0.871; 95% confidence interval [CI], 0.216-3.512; P=0.846). Multivariate analysis revealed serum protein level to be the only predictor of unresponsiveness to the second-line treatment (OR, 0.160; 95% CI, 0.028-0.911; P=0.039). Receiver operating characteristic curve analysis to determine predictors of unresponsiveness to the second dose of IVIG showed a sensitivity of 100% and specificity of 72% at a serum protein cutoff level of <7.15 g/dL. Conclusion: The serum protein level of the patient prior to the second dose of IVIG is a significant predictor of unresponsiveness. The addition of methyl prednisolone to the second-line regimen produces no treatment benefit.
Rotimi, Oluwakemi A.;Rotimi, Solomon O.;Oluwafemi, Flora;Ademuyiwa, Oladipo;Balogun, Elizabeth A.
Toxicological Research
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v.34
no.3
/
pp.211-220
/
2018
Early life exposure to aflatoxin B1 (AFB1) and low protein diet through complementary foods during weaning is common in parts of Africa and Asia. This study evaluated the effect of co-exposure to AFB1 and low protein diet on the extrahepatic tissues of rats. Twenty-four three-week old weanling male albino rats were used for this study and were randomly assigned into four groups: group 1 served as control and was fed normal protein diet (20% protein), group 2 was fed low protein diet (5% protein), group 3 was fed normal protein diet + 40 ppb AFB1 while group 4 received low protein diet + 40 ppb AFB1, all for eight weeks. Afterward, biomarkers of anemia (packed cell volume (PCV), hemoglobin) and kidney function (urea, uric acid, and creatinine) were determined in the blood while biomarkers of oxidative stress were determined in the tissues spectrophotometrically. Co-exposure to AFB1 and low protein diet significantly (p < 0.05) decreased body weight gain and PCV, increased biomarkers of kidney functions and induced oxidative stress in the tissues studied. There was significant (p < 0.05) reduction in glutathione concentration while TBARS was significantly increased in the tissues. Co-exposure to AFB1 and low protein diet had additive effects on decreasing the weight gain and potentiation effect of kidney dysfunction in the rats. The co-exposure also decreased antioxidant enzymes and increased oxidant status in the tissues. Our results demonstrate that this co-exposure has deleterious health effects on extrahepatic tissues and should be a public health concern especially in developing countries where AFB1 contamination is common.
To determine the prognostic factors for survival of dogs infected with canine parvovirus, clinical and laboratory data of 35 dogs with clinical signs compatible with canine parvoviral enteritis admitted to the Veterinary Medical Teaching Hospital, Seoul National University during the period 1997-1998 were collected. Dogs were grouped by some major covariates, which can be considered as guides to the relative prognosis of dogs in the different subgroups. The Kaplan-Meier survival analysis and Weibull proportional hazard model were used to estimate overall survival, evaluate the comparability between groups, and identify potential prognostic factors. The overall survival rate for all dogs was 45.7% over the study period, and the Kaplan-Meier estimate of one week survival was 0.4989. Gender was the most favorable prognosis ; male dog (median, 6 days) had significantly higher risk of dying than female dog (median, 17 days ; p = 0.0023). In addition to gender, age was significantly associated with survival, with juvenile dogs less than 6-month-old having higher risk (p = 0.0359). Dogs that vaccinated with complete protocol (p = 0.0374) and those of having higher value of mean corpuscular volume (p = 0.0346) were found to be of prognostic importance. The 7 dogs in which white blood cell count of less than 2000 had shorter median survival time (3 days) than the remaining 28 dogs (8 days), but no statistical significance was found between leukopenic and survival. The distribution of packed cell volume and hemoglobin measurement was such that the overall risk of dying in the two groups was comparable. Further studies are needed to more accurately assess these results.
To evaluate the effect of cereal supplementation on children's iron nutritional status of Korean institutionalized was designed. Dietary survey was carried out methods of food weighting in the breakfast or/and dinner, and record interview in lunch (n=74). A nutritional intervention study was carried out through supplementing cereal for 4 weeks in 24 children of 1 institution from 4 to 12 years. The children received 3.6mg elemental Fe(as 100g cereal) per day. Blood samples were drawn before and after supplementation. Nutrients which children's intake was less than two-thirds of Korean RDA were Vit A, Vit B1, Vit B2, Ca and Fe. The mean daily intakes of iron were 5.1mg for male and 4.9mg for female and 52.3% for male and 45.4% for female of Korean RDA. The proportions of children with iron depletion assessed by TIBC(>360mg/dl) and serum ferritin(<20ng/ml) were 56.6% and 58.7%, respectively. The proportions of children with the iron deficient erythropoiesis assessed by serum iron(<70ml/dl), Hb(<12g/dl), and Hct(<36%) were 76.0%, 58.7%, and 64.0%, respectively. After cereal supplementation, in anemic children, levels of Hct(p<0.001), serum iron(p<0.001) and transferrin saturation(p<0.001) were significantly increased. The effect of cereal supplementation in children with iron deficient erythropoeisis was more effective to improve the iron nutritional status than children with iron depletion. It was concluded that cereal supplementation program in anemic children was also effective to improve iron nutritional status.
Purpose: The clinical presentations of inflammatory bowel disease (IBD) prior to diagnosis are so diverse or vague that many of them waste time before final diagnosis. This study was undertaken to know the medical history of the pediatric patients until the final diagnosis could be reached. Methods: The medical records of all pediatric patients who were diagnosed with IBD (Crohn's disease [CD] in 14 children, ulcerative colitis [UC] in 17) during the last 13 years were reviewed. We investigated the length of the diagnostic time lag, chief clinical presentation, and any useful laboratory predictor among the routinely performed examinations. Indeterminate colitis was not included. Results: The mean ages of children at the final diagnosis was similar in both diseases. As for the pre-clinical past history of bowel symptoms in CD patients, 5 were previously healthy, 9 had had 1-3 gastrointestinal (GI) symptoms, weight loss, bloody stool, anemia and rectal prolapse. With UC, 9 were previously healthy, 8 had had 1-3 GI symptoms, bloody stool, anorexia. The average diagnostic time lag with CD was 3.36 months, and with UC 2.2 months. Body mass index (BMI) and the initial basic laboratory data (white blood cell, hemoglobin, mean corpuscular volume, serum albumin, and serum total protein) were lower in CD, statistically significant only in BMI. Conclusion: IBD shows diverse clinical symptoms before its classical features, making the patients waste time until diagnosis. It is important to concern possibility of IBD even in the mildly sick children who do not show the characteristic symptoms of IBD.
The traumatic hepatitis and splenitis were experimentally induced in Korean native goats. General examinations, hematological and blood biochemical findings were investigated up to 10 days after induction of traumatic hepatitis and splenitis. Body weight of goats with traumatic hepatitis and splenitis showed no change or only a slight decrease. Changes in body temperature and respiratory rate were not noted in both experimental groups. Heart rate hart not been changed in traumatic splenitis group but were a little increased in traumatic hepatitis group. Erythrocytic series such as erythrocyte counts, hemoglobin concentration and packed cell volume showed same variation within normal range during the period of observation. Total leucocyte counts showed the considerable increase in both experimental groups. The increase of the percentage of neutrophil and the decrease of the percentage of lymphocyte were more remarkable in traumatic hepatitis group than that of traumatic splenitis group. Serum aspartate transferase activity was increased in both experimental groups after surgery, while serum alkaline phosphatase activity has been decreased conciderably up to 7 days after surgery. Serum lactic dehydrogenase activity has been increased up to 3 days after operation and thereafter the activity has returned to normal level in traumatic hepatitis group and the activity increased only the first day after surgery in traumatic splenitis group. There were no changes in total protein and albumin contents in both experimental groups during the period of observation. Serum total cholesterol contents showed a slight increase in both experimental groups and the range of increase in traumatic hepatitis group was more wide. Serum bilirubin contents were net changed in traumatic hepatitis group, but showed a slight increase in traumatic splenitis group.
A simple method for determining the absorption coefficient of oxyhemoglobin and deoxyhemoglobin in human blood is proposed as an application of the complex propagation constant of a guided wave in a thin-film optical waveguide. A serial multichannel sample chamber is constructed on the waveguide to vary the interaction length between the evanescent field and the sample, and the dependence of the sensor response on the interaction length is investigated for the various concentration of two hemoglobins. The sensor response is linearly proportional to the interaction length and the concentration of two hemoglobins. The attenuation constant due to the evanescent field absorption between the samples is experimentally obtained with the designed sensor, and then the absorption coefficient is determined by the proposed method. The absorption coefficients determined by the proposed method fairly well coincided with those obtained by the conventional transmission measurement.
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