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Five Most Common Prognostically Important Fusion Oncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

  • Awan, Tashfeen;Iqbal, Zafar;Aleem, Aamer;Sabir, Noreen;Absar, Muhammad;Rasool, Mahmood;Tahir, Ammara H.;Basit, Sulman;Khalid, Ahmad Mukhtar;Sabar, Muhammad Farooq;Asad, Sultan;Ali, Agha Shabbir;Mahmood, Amer;Akram, Muhammad;Saeed, Tariq;Saleem, Arsalan;Mohsin, Danish;Shah, Ijaz Hussain;Khalid, Muhammad;Asif, Muhammad;Haq, Riazul;Iqbal, Mudassar;Akhtar, Tanveer
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5469-5475
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    • 2012
  • Background and Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. Method: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival ($43.7{\pm}4.24$ weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). Conclusions: This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.

Effect of Reduced N Application and Planting Density on Paddy Rice (수도에 대한 질소감량시비 및 재식밀도의 영향)

  • Hong, Ki-Chang;Shim, Jae-Han;Seo, Yong-Tack;Park, Ro-Dong;Kim, Kil-Yong;Shon, Boe-Kyun;Kim, Yong-Woong
    • Korean Journal of Soil Science and Fertilizer
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    • v.32 no.1
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    • pp.12-21
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    • 1999
  • This study was carried out to improve the cultivation method of paddy rice when the application amount of nitrogen decreased. We investigated the growth and the yield of paddy rice, the changes of nutrients in the soil solution, soil and paddy rice. The results are as follows. The yield at the N4 plot(N $73kg\;ha^{-1}$) was higher than that of control(N $110kg\;ha^{-1}$). N1(N $55kg\;ha^{-1}$), N2(N $55kg\;ha^{-1}$), and N3(N $73kg\;ha^{-1}$). The number of panicle per square meter at the N4 plot was larger than that of control plot. The increase in yield at the N4 plot was due to increased number of panicle where planting density was two times higher compared to the control plot. The availability of nitrogen at the N4 plot also was two times higher than that of control plot. The pH in soil solution was around 7 and did not change largely. The $K^+$ concentration in soil solution at all plots decreased gradually. The $Ca^{2+}$ concentration in soil solutions increased gradually, and decreased at the later stage slightly. The P concentration in soil solution decreased gradually, increased after the heading stage, and then decreased due to decrease of soil temperature. Leaching of $Ca^{2+}$ was higher, while that of $K^+$ and P was lower compared to other ions. Total content of nutrients in soil after harvest decreased. Contents of total N, total P, and O.M. at the N4 plot were higher than those of the other plots. The content of total N and O.M. was correlated to yield. Contents of N, P and K in rice straw and grain at the N4 plot were the highest among all plots. In conclusion, to decrease N application amount in paddy rice cultivation as well as to maintain yield, planting density should be twice of control and the amount of application of N fertilizer should be two-third of control where N fertilizer should be applied mainly at 20 and 10 day before heading.

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The Usefulness of PCR Study in AFB Smear Negative Patients on Admission (내원시 항산균도말검사상 음성인 환자에서 실시한 PCR검사방법의 유용성에 대한 연구)

  • Kim, C.S.;Son, H.D.;Park, M.R.;Seo, J.Y.;Cho, M.D.;Rheu, N.S.
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.5
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    • pp.1001-1010
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    • 1997
  • Background : PCR technique is useful in diagnosis of pulmonary tuberculosis. But, its sensitivity and specificity is some different among several studies. Our aim is compare our PCR results with other's previous PCR results in AFB smear negative patients. Methods : PCR were performed in patients that their disease were suspected as active pulmonary tuberculosis and that their initial serial sputum AFB smear results were negative. Total number of patients studied by PCR technique was 177. Also, we analyzed the data only in patients whose bronchial washing fluid AFB smear was negative. And the primer had been used was IS 6110. Results : In our retrograde study, the number of patients who are diagnosed as having active pulmonary tuberculosis, inactive pulmonary tuberculosis and nontuberculous pulmonary disease was 99, 28, 50, respectively. In the sputum study, the sensitivity of PCR is 41.5% (27 PCR positive cases/65 active TBc cases). And the sensitivity of TB culture is 53.8% (35 TB culture positive cases/65 active TBc cases). In the bronchial washing specimen study, the sensitivity of PCR is 53.8% (21 PCR positive cases/39 active TBc cases). And the sensitivity of TB culture is 43.6% (17 TB culture Positive cases/39 active TBc cases). The specificity of PCR in our study is 94.9%. (74 PCR negative cases/78 inactive TBc or nontubereulous cases) In the cases of patients who were never takened anti-TBc medication, the sensitivity of PCR (45.6%--25 positive cases/55 cases) is some lower than culture (58.2%--32 positive cases/55 cases). In the cases of patients who had been takened anti-TBC medication. the sensitivity of PCR (60%--18 positive cases/30 cases) is some superior than culture (50%--15 positive cases/30 cases). Conclusion : We think that PCR results in cases of sputum AFB smear negative patients is nearly same as culture. And PCR is especially useful in patients who had been takened anti-TBc medication on admission.

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Effect of Compost Application on Yield and Chemical Components of Chinese Cabbage(Brassica pekinensis Rupr.) and Changes of Soil Physico-chemical Properties in Organic Farming (유기농산물 생산을 위한 퇴비시용이 배추의 수량과 무기성분 및 토양의 이화학성에 미치는 영향)

  • Lee, Joo-Sam;Chang, Ki-Woon;Cho, Sung-Hyun;Kim, Chong-Yun
    • Korean Journal of Soil Science and Fertilizer
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    • v.29 no.4
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    • pp.365-370
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    • 1996
  • To get the basic data for organic farming, the Chinese cabbage(Brassica pekinensis Rupr.) was cultivated in field of sandy loam soil and compost was applied at the ratios of 0, 20, 40, 80, 120ton per ha, respectively, with N-P-K elements. The yield of Chinese cabbage was maximum in the plot of compost 40t/ha application and it's weight was 3,783g/head. The chemical components of Chinese cabbage were no remarkable changes with the increasing amount of compost application. Content of organic matter in soil after experiment was finished was 39g/kg, total nitrogen was 2.2g/kg, available phosphorus was 1,927mg /kg. CEC was $11.4cmol^+/kg$, exchangable cations were K:0.5. Ca:0.6. Mg:0.3 and $Na:0.2cmol^+/kg$ in treatment of compost 120 t/ha.

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A Study on the Development of an Instrument for Evaluating the Quality of Nursing Care (간호의 질 평가도구 개발에 관한 일 연구)

  • 유지수
    • Journal of Korean Academy of Nursing
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    • v.7 no.2
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    • pp.11-21
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    • 1977
  • Many in nursing look back on Nursing Research history and proudly point to the fact that emphasis in nursing research has changed from studying the nurse to studying nursing practice. In recent years, much emphasis has been placed on seeking a method of evaluating the quality of nursing care. In spite of these attempts, however, an instrument for evaluating the quality of nursing care that is actually applicable in the clinical area has not been found. The Purposes of this study are as follows: 1) To develop the instrument to be used in evaluating the quality of nursing care provided in the Neuro - Surgery Constant Care Unit of Severance Hospital 2) To evaluate the quality of nursing care in the clinical area. 3) To provide the necessary information for improvement of quality of nursing care. The instrument for evaluating the quality of nursing care, developed by the investigator, was composed of 7 nursing goals and divided into 65 standards of nursing performance. The 7 nursing goal are as follows : 1) Maintenance of airway 2) Maintenance of fluid at electrolyte balance 3) Maintenance of elimination 4) Personal hygiene 5) Optimum activity 6) Prevention of accidents 7) Emotional care The study population defined was composed of all the case (51) who were admitted in the Neuro- Surgery Constant Care Unit of Severance Hospital from May 7-13, 1976. The observation method was used and the data was subjected to the %, X²-test, T-test, F-test and Correlation. The results of tile study were as follows : 1. Levels of nursing performance regarding nursing goals. Seven different nursing care indices were constructed in terms of nursing goals. The index scores were grouped arbitrarily into ,j categories such as "excellent", "good", "moderate", "incomplete", and "poor"based upon the investigator′s personal judgement. a. The nursing index of maintaining airway showed that 78% of the patients fell within the "excellent" and 22% of the patients, fell within the "good" category. b. The nursing index of maintaining fluid & electrolyte balance showed that 95% of the patients fell within the "excellent" and 5 % of the patients fell within the "good" category. c. The nursing index of maintaining elimination showed that 100% of the patients fell within the "excellent" category. d. The nursing index of personal hygiene revealed that 49% of the patients fell within the "excellent" and 51% of the patients fell within the "good" category. e. The nursing index of optimum activity showed that 63% of the patients fell within the "excellent" and 32% of the patients fell within tile "good" and 5% of patients fell within the "moderate" category. f. The nursing index of prevention of accidents showed that 100% of the patients foil within the "excellent" category. g. The nursing index of emotional cart revealed that 27% of the patients fell within the "excellent", 24 % of the patients fell within tile "good", 29 % of the patients fell within the "incomplete" category. From these findings it is disclosed that the quality of nursing care provided in the Neuro- Surgery Constant Care Unit of Severance Hospital was excellent. h. There were statistically significant differences between the nursing index of physical care and emotional care. (t=8.73, D. F. =100. p<0.01) It is revealed that more physical care then emotional care was carried out by nurses. 2. Levels of nursing performance regarding general characteristics of the patients. No significant differences were observed statistically with the nursing indices of nursing goals according to the sex (t=0.084, D. F. =12, p>0.05). Age (F=0.1251, D. F. : 3.18. p 〉0.05), absence or presence of operating experiences (t=0.6032, D. F. =12, p〉0.05, levels of consciousness (F=0.31, D. F. :3. 18, p >0.05) 3. Relationship between the levels of consciousness and the nursing index of each nursing goal. There was negative correlation between the levels of consciousness and the nursing index of maintaining airway (r=-0. 5449, p<0.01) and personal hygiene (r= -0.4075, p<0.01) There was positive correlation between the levels of consciousness and the nursing index of optimum activity (r=0.3936, p <0.01) and emotional care (r=0.7819, p〈0.01). There was slight correlation between the levels of consciousness and the nursing index of maintaining fluid & electrolyte balance (r=-0.3418, 0.010.05) and preventing accidents (r=0.1441, p>0.05.

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Prognostically Significant Fusion Oncogenes in Pakistani Patients with Adult Acute Lymphoblastic Leukemia and their Association with Disease Biology and Outcome

  • Sabir, Noreen;Iqbal, Zafar;Aleem, Aamer;Awan, Tashfeen;Naeem, Tahir;Asad, Sultan;Tahir, Ammara H;Absar, Muhammad;Hasanato, Rana MW;Basit, Sulman;Chishti, Muhammad Azhar;Ul-Haque, Muhammad Faiyaz;Khalid, Ahmad Muktar;Sabar, Muhammad Farooq;Rasool, Mahmood;Karim, Sajjad;Khan, Mahwish;Samreen, Baila;Akram, Afia M;Siddiqi, Muhammad Hassan;Shahzadi, Saba;Shahbaz, Sana;Ali, Agha Shabbir
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3349-3355
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    • 2012
  • Background and objectives: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. Methods: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL1 positive patients had frequent organomegaly and usually presented with a platelets count of less than $50{\times}10^9/l$. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. Conclusions: This is the first study from Pakistan which investigated the frequency of5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.

Germination-Induced Changes in Flavoring Compound Profiles and Phytonutrient Contents in Scented Rice (향미벼의 발아 전 후 향기 성분 및 기능성 지질성분 함량의 변화)

  • Mahmud, MM Chayan;Das, Animesh Chandra;Lee, Seul-Ki;Kim, Tae-Hyeong;Oh, Yejin;Cho, Yoo-Hyun;Lee, Young-Sang
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.61 no.4
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    • pp.242-250
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    • 2016
  • Although rice has been cultivated as a major food crop for approximately 5,000 years, the interest of customers in 'scented rice' is a recent trend in the Korean market. As a part of developing a germinated scented rice variety, the newly bred scented rice variety 'Cheonjihyang-1 se' was germinated for 24 h, and changes in profiles of flavor-related volatiles, lipophilic phytonutrients, and fatty acids were investigated. The profiling of volatile compounds by using a headspace-gas chromatography-mass spectrometry (HS-GC-MS) revealed a total of 56 odor-active flavoring compounds; 52 at the pre-germination stage, 51 at the post-germination stage, and 47 common at both stages. The major flavoring compounds were nonanol and benzene, which constituted 11.5% and 6.6%, respectively, of the total peak area in pre-germinated rice, and 19.4% and 6.5%, respectively, in post-germinated rice. Germination induced an increase in 13 flavoring compounds, including 3,3,5-trimethylheptane and 1-pentadecene, which increased by 763 and 513%, respectively by germination. However, we observed a germination-induced decrease in most of the other flavoring compounds. Especially, the most important scented rice-specific popcorn-flavoring compound, 2-acetyl-1-pyrroline, showed 89% decrease due to germination. Furthermore, the germination of scented rice induced a decrease in the content of various phytonutrients. For example, the total contents of phytosterols, squalene, and tocols decreased from 207.97, 31.74, and $25.32{\mu}g\;g^{-1}$ at pre-germination stage down to 136.66, 25.12, and $17.76{\mu}g\;g^{-1}$, respectively at post-germination stage. The fatty acid compositions were also affected by germination. The composition of three major fatty acids, linoleic, oleic, and palmitic acids, increased from 36.6, 34.2, and 24.4%, respectively, at the pre-germination stage to 37.9, 36.9, and 20.7%, respectively, at the post-germination stage. All these results suggested significant changes in the flavor-related compounds and phytonutrients of the scented rice variety 'Cheonjihyang-1 se' during the process of germination, and subsequently the need for developing a more precise process of germination to enhance the flavor and nutritional quality of the germinated scented rice products.

Cellular Mechanism of Nicotine-mediated Intracellular Calcium Homeostasis in Primary Culture of Mouse Cerebellar Granule Cells (니코틴의 마우스 소뇌과립세포내 칼슘의 항상성 조절기전)

  • Kim, Won-Ki;Pae, Young-Sook
    • The Korean Journal of Pharmacology
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    • v.32 no.1
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    • pp.13-21
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    • 1996
  • Intracellular calcium concentration ($[Ca^{2+}]_i$) may play a crucial role in a variety of neuronal functions. Here we report that in primary culture of mouse cerebellar granule cells nicotinic acetylcholine receptors (nAChRs) are expressed in a specific developmental stage and involved in the regulation of intracellular calcium homeostasis. Nicotine-mediated calcium responses were measured using $^{45}Ca^{2+}$ or fluorometrically using the calcium-sensitive fluorescent dye fura-2. Maximal uptake of $^{45}Ca^{2+}$ evoked by nicotine in mouse cerebellar granule cells were revealed $8{\sim}12$ days in culture. In contrast, nicotine did not alter the basal $^{45}Ca^{2+}$ uptake in cultured glial cells. In cerebellar granule cells nicotine-evoked $^{45}Ca^{2+}$ uptake was largely blocked by the NMDA receptor antagonists. Glutamate pyruvate transaminase (GPT). which removes endogenous glutamate, also prevented nicotine effects, implying the indirect involvement of glutamate in nicotine-mediated calcium responses. Fluorometric studies using fura-2 showed two phases of nicotine-evoked $[Ca^{2+}]_i$ rises: the initial rising phase and the later plateau phase. Interestingly, the NMDA receptor antagonists and GPT appeared to inhibit only the later plateau phase of nicotine-evoked $[Ca^{2+}]_i$ rises. The present results imply that nicotine mediated $^{45}Ca^{2+}$ uptake and $[Ca^{2+}]_i$ rises are attributed to the calcium fluxes through both nAchRs and NMDA receptors in a time-dependent manner. Consequently, nAChRs may play an important role in neuronal development by being expressed in a specific developmental stage and regulating the intracellular calcium homeostasis.

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Effect of Dietary Betaine and Energy Levels on Liver Fats and Cholesterol in Laying Hens (사료내 비태인과 에너지 수준이 산란계의 간지방과 콜레스테롤에 미치는 영향)

  • Park J. H.;Park S. Y.;Ryu K. S.
    • Korean Journal of Poultry Science
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    • v.32 no.3
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    • pp.149-156
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    • 2005
  • Two experiments were conducted to examine the effects of betaine intake on blood and yolk cholesterol, abdominal fat, liver fat, tissue triglyceride(TG) and liver HMG-CoA reductase In laying hens. In Expt. 1, a total of 72 ISA-brown laying hens were individually assigned into four treatments from 18 to 21 weeks old. Com-soybean meal based diet were fed with the addition of 0, 300, 600 and 1,200ppm. In Expt. 2, 72 ISA-brown laying hens were housed into individual cage to evaluate the effect of dietary betaine(0, 600ppm) and energy(ME, 2,800, 2,900kca/kg) from 70 to 74 weeks. Serum total cholesterol, LDL and HDL-cholesterol and TG concentration in blood of hens fed betaine tended to increase compared to those of the control, but were not significantly different. However, betaine supplementation showed a statistically significant decrease in yolk cholesterol(P<0.05). There was no significant difference in abdominal fat among the treatments. Liver fats and 7c of birds 130 betaine was decreased compared with control. Serum total cholesterol, LDL-cholesterol and triglyceride concentration were significantly inc.eased by ffeding a diet containing 600ppm betaine in Expt. 2(P<0.05), but were not influenced by the dietary energy levels. Yolk cholesterol, abdominal fat and HMG-CoA reductase activity were affected neither by dietary energy nor betaine level.

Studies on intrauterine factors influencing on implantation of embryo (수정란 착상에 영향을 미치는 자궁내인자에 관한 연구)

  • Lee, Sung-soo;Kwun, Jong-kuk
    • Korean Journal of Veterinary Research
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    • v.32 no.4
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    • pp.531-542
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    • 1992
  • The present study was performed to identify the factors influencing on early pregnacy and embryo implantation in rabbit. Serum, uterine fluid, and uterine tissue were collected on day 0, 3, 5, 7 and 9 of pregnancy. The intrauterine environment of receptive phase and refractory phase was compared by measuring protein synthetic capacity of endometrium, amino acid composition and concentrations of lipids(phospholipid, cholesterol). The results obstained were as follows : 1. The concentrations of total protein were significantly increased (p<0.01) on day 5 ($7.00{\pm}0.55$), 7($6.29{\pm}0.65$), and 9($6.34{\pm}0.61$), compared to those on day 0($5.50{\pm}0.12g/100m{\ell}$) in serum. The concentration of albumin on day 0 was $0.81{\pm}0.05$ and reached maximum on day 5 ($1.59{\pm}0.07g/100m{\ell}$) in serum. The concentrations of total protein were significantly increased(p<0.01) on day 5($1.56{\pm}0.10$), 7($1.99{\pm}0.22$), compared to those on day 0($0.38{\pm}0.02g/100m{\ell}$) in uterine fluid. The concentration of albumin on day 5($0.78{\pm}0.05g/100m{\ell}$) was higher than those on the other days in uterine fluid. 2. The incorporation rates of [$^3H$]-leucine into protein were significantly increased(p<0.01) on day 5 ($919.6{\pm}97.5$), 7($1445.4{\pm}95.9$) and 9($450.38{\pm}28.71$), compared to those on day 0($328.2{\pm}38.9cpm/mg$ protein) in endometrium. The incorporation rates in colehicine-treated endometrium on day 5 ($1341.9{\pm}73.8$), 7($1729.4{\pm}63.3cpm/mg$ protein) were significantly higher(p<0.01) than those on the other days. 3. The compositions of amino acid were not distinctly changed during early pregnancy in serum. The composition ratios of methione, lysine were distinctly decreased on day 3, compared to those on day 0 in uterine fluid. Those of glycine, alanine were increased on day 9, compared to those on other days but his tidine decreased in uterine fluid. 4. The concentrations of total phospholipid and total cholesterol were significantly decreased(p<0.01) on day 3($77.9{\pm}15.5$, $61.5{\pm}21.2$), compared to those on day 0($164.0{\pm}33.9$, $167.2{\pm}46.2mg/100m{\ell}$)in serum. The concentrations of total phospholipid and total cholesterol on day 9 ($47.3{\pm}13.4$, $37.7{\pm}9.6mg/100m{\ell}$) were significantly higher(p<0.01) than those on the other days in uterine fluid. 5. Total phopholipid/total cholesterol ratios were not significantly changed during early pregnancy in serum. However, total phospholipid/total cholesterol ratios on day 5 ($2.00{\pm}0.42$), 7 ($1.11{\pm}0.77$) and 9 ($1.47{\pm}0.30$) were higher than those on day 3($0.84{\pm}0.41$) in uterine fluid. 6. The concentrations of phosphatidylcholine and phosphatidylserine were significantly increased (p<0.01) on the other days, compared to those on day 0 during early pregnancy in serum. The concentrations of phosphatidylcholine were significantly increased(p<0.01),compared to those on day 0 and those of phosphatidyl-ethanolamine were consistently increased but not significant in early pregnancy in uterine fluid.

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