• Title/Summary/Keyword: Acute phase response

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DNA Ploidy and S-phase Fraction Analysis in Paediatric B-cell Acute Lymphoblastic Leukemia Cases: a Tertiary Care Centre Experience

  • Kumar, Banothu Kiran;Bhatia, Prateek;Trehan, Amita;Singh, Ajit Pal;Kaul, Deepak;Bansal, Deepak
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7917-7922
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    • 2015
  • DNA ploidy is an important prognostic parameter in paediatric B-ALL, but the significance of the S-phase fraction is unclear. In present study, DNA ploidy was assessed in 40 pediatric B-ALL cases by flow cytometry. The DI (DNA index) and percentage of cells in S-phase were calculated using Modfit software. Aneuploidy was noted in 26/40 (65%) cases. A DI of 1.10-1.6 (hyperdiploidy B) was noted in 20/40 (50%) and 6/40 (15%) had a DI>1.60 (triploid and tetraploid range). Some 14/40 (35%) cases had a diploid DI between 0.90-1.05. None of the cases had a DI <0.90 (hypodiploid) or in the 1.06-1.09 (hyperdiploid A) range. The mean S-phase fraction was 2.6%, with 24/40 (60%) having low and 16/40 (40%) high S-phase fractions. No correlation was noted with standard ALL risk and treatment response factors with DI values or S-phase data, except for a positive correlation of low S-phase with high NCI risk category (p=0.032). Overall frequency of hyperdiploidy in our cohort of B-ALL patients was very high (65%). No correlation between hyperdiploidy B and low TLC or common B-phenotype was observed in our study as 42% cases with DI 1.10-1.6 had TLC> $50{\times}10^9$ and 57.1% CD 10 negativity. The study also highlighted that S-phase fraction analysis does not add any prognostic information and is not a useful parameter for assessment in ALL cases. However, larger studies with long term outcome analysis are needed to derive definitive conclusions.

Low Dose Cisplatin as a Radiation Sensitizer in Management of Locally Advanced Scluamous Cell Carcinoma of the Uterine Cervix : Evaluation of Acute Toxicity and Early Response (국소 진행된 자궁경부암의 방사선치료와 저용량 cisplatin 항암요법 동시치료시 급성독성 밀 초기반응 평가)

  • Kim Hunjung;Cho Young Kap;Kim Chulsu;Kim Woo Chul;Lee Sukho;Loh J K
    • Radiation Oncology Journal
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    • v.17 no.2
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    • pp.113-119
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    • 1999
  • Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.

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Expression of Toll-like Receptor-2 on the Peripheral Blood Monocytes in Kawasaki Disease Patients (가와사끼병 환자에서 분리한 CD14양성 세포에서 Toll-like Receptor-2의 발현)

  • Hwang, Dae Hwan;Han, Jung Woo;Choi, Kyung Min;Shin, Kyung Mi;Kim, Dong Soo
    • Clinical and Experimental Pediatrics
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    • v.48 no.3
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    • pp.315-320
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    • 2005
  • Objective : Toll like receptor(TLR) is known to be involved in innate immunity. Many microbial antigens stimulate TLR, and as a result of intracellular signal transduction, they activate nuclear factor-kB which produces diverse inflammtory cytokines. Until now, many research topics in Kawasaki disease focused on cytokine increasement. In this study, we aim to reveal TLR increasement which might be associated with initiation of inflammatory response. Methods : We obtained the peripheral blood of ten patients who were diagnosed with Kawasaki disease in Yonsei University College of Medicine from March 2003 to August 2003, as well as those of a febrile control group and the same number of a normal control group. Flow cytometry was done in all samples for quantification of TLR-2 expression in CD14 positive monocyte. And we also extracted total RNA of periphral monocyte and quantificated expression of TLR-2 mRNA by RT-PCR. Results : The expression of TLR-2 in Kawasaki disease increased significantly compared with the normal control group but not when compared with the febrile control group. And the expression decreased slightly in the subacute phase of Kawasaki disease compared with the acute phase, but this was statistically insignificant. mRNA expression of TLR-2 in peripheral blood monocyte also increased in the acute phase of Kawasaki disease. Conclusion : Expression of TLR-2 in Kawasaki disease increased when compared with the normal control group, which means that innate immunity is associated with the pathogenesis of Kawasaki disease.

Hemolytic uremic syndrome (용혈성 요독 증후군)

  • Park, Hye Won
    • Clinical and Experimental Pediatrics
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    • v.50 no.10
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    • pp.931-937
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    • 2007
  • The hemolytic uremic syndrome (HUS) is a rare disease of microangiopathic hemolytic anemia, low platelet count and renal impairment. HUS usually occurs in young children after hemorrhagic colitis by shigatoxin-producing enterohemorrhagic E. coli (D+HUS). HUS is the most common cause of acute renal failure in infants and young children, and is a substantial cause of acute mortality and morbidity; however, renal function recovers in most of them. About 10% of children with HUS do not reveal preceding diarrheal illness, and is referred to as D- HUS or atypical HUS. Atypical HUS comprises a heterogeneous group of thrombomicroangiopathy (TMA) triggered by non-enteric infection, virus, drug, malignancies, transplantation, and other underlying medical condition. Emerging data indicate dysregulation of alternative complement pathway in atypical HUS, and genetic analyses have identified mutations of several regulatory genes; i.e. the fluid phase complement regulator Factor H (CFH), the integral membrane regulator membrane cofactor protein (MCP; CD46) and the serine protease Factor I (IF). The uncontrolled activation of the complement alternative pathway results in the excessive consumption of C3. Plasma exchange or plasma infusion is recommended for treatment of, and has dropped the mortality rate. However, overall prognosis is poor, and many patients succumb to end-stage renal disease. Clinical presentations, response to plasma therapy, and outcome after renal transplantation are influenced by the genotype of the complement regulators. Thrombotic thrombocytopenic purpura (TTP), another type of TMA, occurs mainly in adults as an acquired disease accompanied by fever, neurologic deficits and renal abnormalities. However, less frequent cases of congenital or hereditary TTP associated with ADAMTS-13 (a disintegrin and metalloprotease, with thrombospondin 1-like domains 13) gene mutations have been reported, also. Recent advances in molecular genetics better allow various HUS to be distinguished on the basis of their pathogenesis. The genetic analysis of HUS is important in defining the underlying etiology, predicting the genotype-related outcome and optimizing the management of the patients.

Clinical Study of Acute and Chronic Pain by the Application of Magnetic Resonance Analyser $I_{TM}$ (자기공명분석기를 이용한 통증관리)

  • Park, Wook;Jin, Hee-Cheol;Cho, Myun-Hyun;Yoon, Suk-Jun;Lee, Jin-Seung;Lee, Jeong-Seok;Choi, Surk-Hwan;Kim, Sung-Yell
    • The Korean Journal of Pain
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    • v.6 no.2
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    • pp.192-198
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    • 1993
  • In 1984, a magnetic resonance spectrometer(magnetic resonance analyser, MRA $I_{TM}$) was developed by Sigrid Lipsett and Ronald J. Weinstock in the USA, Biomedical applications of the spectrometer have been examined by Dr. Hoang Van Duc(pathologist, USC), and Nakamura, et al(Japan). From their theoretical views, the biophysical functions of this machine are to analyse and synthesize a healthy tissue and organ resonance pattern, and to detect and correct an abnormal tissue and organ resonance pattern. All of the above functions are based on Quantum physics. The healthy tissue and organ resonance patterns are predetermined as standard magnetic resonance patterns by digitizing values based on peak resonance emissions(response levels or high pitched echo-sounds amplified via human body). In clinical practice, a counter or neutralizing resonance pattern calculated by the spectrometer can correct a phase-shifted resonance pattern(response levels or low pitched echo-sounds) of a diseased tissue and organ. By administering the counter resonance pattern into the site of pain and trigger point, it is possible to readjust the phase-shifted resonance pattern and then to alleviate pain through regulation of the neurotransmitter function of the nervous system. For assessing clinical effectiveness of pain relief with MRA $I_{TM}$ this study was designed to estimate pain intensity by the patient's subjective verbal rating scale(VRS such as graded to no pain, mild, moderate and severe) before application of it, to evaluate an amount of pain relief as applied the spectrometer by the patients subjective pain relief scale(visual analogue scale, VAS, 0~100%), and then to observe a continuation of pain relief following its application for managing acute and chronic pain in the 102 patients during an 8 months period beginning March, 1993. An application time of the spectrometer ranged from 15 to 30 minutes daily in each patient at or near the site of pain and trigger point when the patient wanted to be treated. The subjects consisted of 54 males and 48 females, with the age distribution between 23~40 years in 29 cases, 41~60 years in 48 cases and 61~76 years in 25 cases respectively(Table 1). The kinds of diagnosis and the main site of pain, the duration of pain before the application, and the frequency of it's application were recorded on the Table 2, 3 and 4. A distinction between acute and chronic pain was defined according to both of the pain intervals lasting within and over 3 months. The results of application of the spectrometer were noted as follows; In 51 cases of acute pain before the application, the pain intensities were rated mild in 10 cases, moderate in 15 cases and severe in 26 cases. The amounts of pain relief were noted as between 30~50% in 9 cases, 51~70% in 13 cases and 71~95% in 29 cases. The continuation of pain relief appeared between 6~24 hours in two cases, 2~5 days in 10 cases, 6~14 days in 4 cases, 15 days in one case, and completely relived of pain in 34 cases(Table 5~7). In 51 cases of chronic pain before the application, the pain intensities were rated mild in 12 cases, moderate in l8 cases and severe in 21 cases. The amounts of pain relief were noted as between 0~50% in 10 cases, 51~70% in 27 cases and 71~90% in 14 cases. The continuation of pain relief appeared to have no effect in two cases. The level of effective duration was between 6~12 hours in two cases, 2~5 days in 11 cases, 6~14 days in 14 cases, 15~60 days in 9 cases and in 13 cases the patient was completely relieved of pain(Table 5~7). There were no complications in the patients except a mild reddening and tingling sensation of skin while applying the spectrometer. Total amounts of pain relief in all of the subjects were accounted as poor and fair in 19(18.6%) cases, good in 40(39.2%) cases and excellent in 43(42.2%) cases. The clinical effectiveness of MRA $I_{TM}$ showed variable distributions from no improvements to complete relief of pain by the patient's assessment. In conclusion, we suggest that MRA $I_{TM}$ may be successful in immediate and continued pain relief but still requires several treatments for continued relief and may be gradually effective in pain relief while being applied repeatedly.

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Gene Expression Profiling of 6-MP (6-mercaptopurine) in Liver

  • Kim Hyung-Lae;Kim Han-Na;Lee Eun-Ju
    • Genomics & Informatics
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    • v.4 no.1
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    • pp.16-22
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    • 2006
  • The KFDA (Korea Food & Drug Administration) has performed a collaborative toxicogenomics project since 2003. Its aim is to construct a toxicology database of 12 compounds administered to mice at initial phase. We chose 6-MP (6-mercaptopurine) which has been used in the treatment of childhood leukemia. It was administered at low (0.224 mg/kg) and at high (2.24 mg/kg) dose (5 mice per group) intraperitonealy to the postnatal 6 weeks mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after scarification. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to 6-MP induced toxicity, including lipid metabolism abnormality, inflammatory response, oxidative stress, ATP depletion and cell death. The potential toxic effects appearing as gene expression changes are dependent of the time of 6-MP but independent of the dosage of it. This study would contribute to establishment of international database as well as national one about hepatotoxicity.

QCM biosensor for the determination of haptoglobin (헵토글로빈 측정을 위한 수정미소저울 바이오센서 개발)

  • Kim, Sung-Il;Lee, Hyeon-Jeong;Park, Soon-Hyuk;Bhang, Hyun-Soo;Lee, Jin-Ah;Choi, Suk-Jung
    • Journal of Sensor Science and Technology
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    • v.16 no.2
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    • pp.132-141
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    • 2007
  • The purpose this research is to develop QCM (quartz crystal microbalance) biosensor for the determination of haptoglobin. Haptoglobin is an acute-phase protein with a hemoglobin-binding activity and has a potential to be used as a biomarker for infection or cancer. Haptoglobin level in milk has been used for the diagnosis of cow mastitis. In this study, anti-bovine haptoglobin antibody or bovine hemoglobin was chemically immobilized on the surface of the QCM, and the resulting sensor chips were tested for their response to samples containing haptoglobin at different concentrations. Concentration dependent frequency change was observed with both of the sensor chips. Especially, the sensor chip containing anti-bovine haptoglobin antibody showed sufficient sensitivity in the concentrations typically observed in the cows with mastitis.

Efficacy of Oral Korean Red-ginseng on sCRP and Soreness after Muscle Damage

  • NA, Hyun-Jong
    • The Journal of Korean Medicine
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    • v.26 no.4
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    • pp.39-45
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    • 2005
  • Objectives: The study investigated the efficacy of oral Korean red-ginseng (RG) on sCRP response mediated by eccentric contraction-induced muscle damage and discussed its mechanism. Methods: Nineteen healthy young subjects (aged 24.4$\pm$2.07 yr) volunteered for this double blind test. They were classified into either the RG group (N=10) or placebo (P) group (N=9) during the 10-d experimental protocol. Blood samples were collected on T1 (baseline), T1 (1h), T2 (1d), T3 (2d) and T4 (3d) after eccentric contraction-induced injury on the seventh day. Statistical analyses were conducted using nonparametric methods (p<0.05). Results: The RG group increased sCRP more than P group and didn't increase soreness peak at T2, not significant. There were no correlations between soreness intensity and sCRP. Oral RG had little efficacy for reducing sCRP at the muscle damage-mediated acute phase; rather, it increased because of its proinflammatory cytokine production. Conclusions: Oral RG could stimulate proinflammatory cytokine production, and occasionally bal-pyo-beob could be helpful for the efficient recovery of muscle injury.

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Effects of Brisk Walking and Brisk Walking Plus Diet on C-reactive Protein in Obese Women with Hypertriglycemia (건강걷기, 건강걷기와 식이 교육이 고중성지방혈증 비만 여성의 C-reactive protein에 미치는 영향)

  • Lee, Mi Ra;Kim, Wan Soo
    • Korean Journal of Adult Nursing
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    • v.18 no.4
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    • pp.660-667
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    • 2006
  • Purpose: The purpose of this study was to investigate the effects of 12-week brisk walking and brisk walking plus diet program on C-Reactive Protein(CRP) in middle-aged obese hypertriglycemic($triglyceride{\geq}150mg/d{\ell}$) Korean women. Method: The subjects were 16 obese ($BMI{\geq}25$) hypertriglycemic middle-aged women (7 for brisk walking group, 9 for brisk walking plus diet group) who participated in a health promotion program at one public health center. Initially the brisk walking intervention consisted of walking for 20 minutes/day at an intensity of 40 to 50% of heart rate reserve(HRR) for 3 days/week and progressed to 50 minutes/day, 60 to 70% of their HRR, and 6 days/week. The diet intervention consisted of 60 minutes of group education and 20 to 30 minutes of individual counseling with a nutritionist every week. Data were analyzed with SPSS PC program. Results: There was no significant reduction in CRP levels in both brisk walking (Z=-1.70, p=0.088) and brisk walking plus diet group(Z=-0.31, p=0.752). In brisk walking only group, CRP levels were increased after the intervention. Conclusion: Brisk walking could increase the level of CRP when it is in the course of progression and diet could decrease the acute phase inflammatory response.

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Inhibitory effect of epigallocatechin from Camellia sinensis leaves against pro-inflammatory mediator release in macrophages

  • Cho, Jun-Hyo;Hong, Eun-Jin;Cho, Young-Je
    • Journal of Applied Biological Chemistry
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    • v.60 no.3
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    • pp.199-205
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    • 2017
  • To investigate the anti-inflammatory activity of natural products, we determined the anti-inflammatory activity of purified epigallocatechin (EGC) from Camellia sinensis leaves. In the present study, we found that EGC inhibited the production of proinflammatory mediators (IL-6, TNF-${\alpha}$, NO, and $PGE_2$) in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. Suppression of IL-6 seems to be at least partly attributable to the inhibitory effect of EGC. TNF-${\alpha}$ is a major cytokine produced by LPS-induced macrophages, and they have a wide variety of biological functions including regulation of inflammation. The inhibition of IL-6 and TNF-${\alpha}$ production by EGC may downregulate the acute-phase response to LPS, thereby reducing LPS-induced inflammation. In addition to IL-6 and TNF-${\alpha}$, EGC effectively reduced the production of other key inflammatory mediators, including NO and $PGE_2$. The inhibitory effect of EGC on NO and $PGE_2$ production was supported by the suppression of inducible nitric oxide synthase and COX-2 at protein levels. These results support the traditional use of EGC in the alleviation of various inflammation-associated diseases and suggest that EGC might be useful in the development of new functional foods for inflammatory diseases.