노화기전의 면역학적 접근

김재식,이원길,서장수,송경은,이중원,이난영,Marc E. Weksler 대한임상병리학회 2001 대한임상병리학회지 Vol.21 No.1

Oral Administration of β-Glucosylceramide for the Treatment of Insulin Resistance and Nonalcoholic Steatohepatitis: Results of a Double-Blind, Placebo-Controlled Trial

Gadi Lalazar,Ehud Zigmond,Sarah Weksler-Zangen,Ami Ben Ya’acov,Miriam Sklair Levy,Nilla Hemed,Itamar Raz,Yaron Ilan 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.5

β-glucosylceramide (GC) is a naturally occurring glycosphingolipid that was shown to improve hepatic steatosis, steatohepatitis, and insulin resistance in animal models of nonalcoholic fatty liver disease. In this study, we evaluated the safety and efficacy of oral administration of GC in subjects with nonalcoholic steatohepatitis (NASH). Twenty-three patients with biopsy proven NASH were enrolled in a double-blind, placebo-controlled trial. Patients were orally administered daily with 7.5 mg of GC. Patients were followed for safety, liver enzymes, HbA1c, insulin sensitivity, lipid profile, hepatic fat content as measured by magnetic resonance imaging (MRI), and NASH score on liver biopsy. No treatment-related adverse events were observed during treatment. In a per protocol analysis of data, oral administration of GC decreased the hepatic fat content as measured by MRI in GC-treated compared with placebo. HbA1C decreased in patients treated with GC. GC treatment was associated with a milder decrease in the high-density lipoprotein serum levels. The beneficial effects were associated with a decrease in CD4 and NKT cell subsets of lymphocytes. Due to the small number of subjects enrolled, differences did reach statistical significance. Oral administration of GC is safe and biologically active in patients with NASH and insulin resistance.

노화에 따른 T 및 B 세포의 변화

김재식,이원길,서장수,송경은,이중원,이난영,Marc E. Weksler 경북대학교 병원 2002 경북대학교병원의학연구소논문집 Vol.6 No.1

배경:말초혈 림프구 아형 분석은 면역 상대의 평가와 다양한 질환의 진단 및 추적검사에 널리 시행된다. 일부 림프구 아형은 나이가 증가함에 따라 변화되는 것으로 알려져 있으나 지금까지 나이에 따른 변화를 보고한 바는 거의 없다.이에 저자들은 연령에 따른 각 군별로 흔히 검사되는 림프구 아형 분석을 실시하여 노화에 따라 변화되는 아형을 알아보고자 하였다. 방법:일반혈액검사 상 정상 범위를 보이는 총 302명에 대해 림프구 아형 분석을 실시하였다. Simultest™IMK-Lymphocyte kit를 사용하여 2색상 직접면역형광염색 후 유세포분석법을 시행하였다.분석한 림프구 아형은 T 세포. B 세포,CD4^+ T세포, CD8^+ T세포,CD4^+/CD8^+비율,NK 세포이며,측정한 림프구 수로부터 각 아형의 절대 수를 계산하였다.연령에 따른 각군간의 평균치의 비교는 SAS 6.12를 이용하여 분석하였고,P 값이 0.05 미만인 경우 유의하다고 판정하였다. 결과:각 항목 중 성별 차이를 보였던 항목은 없었으며,연령별로 유의한 차이를 보이지 않았던 항목은 CD4^+ T세포의 백분율의 감소와 총 림프구 수,T 및 B 세포수, CD4^+ 및 CD8^+ T 세포수의 감소를 보인데 비해 NK 세포 백분율의 증가와 CD4^+/CD8^+ 비율의 증가를 보였다. 결론: 노화에 따른 면역학적 변화로 가장 두드러진 특징은 T 및 B 세포가 감소하는 것이다.NK 세포는 노화에 따라 증가되었으며 이는 면역 상태의 악화에 대한 보상으로 나타나는 결과로 사료된다. Background: Lymphocyte subset analysis in peripheral blood is widely performed to assess the immune status and to diagnose and monitor various diseases.Some lymphocyte subsets are known to change with age,but only a little data about age-related changes for these subsets in healthy individuals have been reported.So we attempted to review changes for these subsets with age. Methods: Lymphocyte subset analysis was performed on 302 subjects,189 males and 113 females with age group in all decades of life.Two color direct immunofluorescence flow cytometry(FCM)was done using a Simultest™IMK-Lymphocyte kit(Becton Dickinson,USA),FACScan™(Becton Dickinson,USA)and FACSalibur™(Becton Dickinson,USA).Lymphocyte subsets analysed were T(CD3^+)and B cell(CD19^+),helper/inducer T(CD4^+)and suppressor/cytotoxic T cells(CD8^+),and helper/suppressor(CD4^+/CD8^+)ratio and natural killer(NK)cells(CD3-CD16^+/CD56^+).The absolute numbers of each subset were calculated from the total lymphocyte counts.The data collected was analysed using SAS6.12.A P-value of<0.05 was considered significant. Results: There were no statistically significant differences between male and female subjects.The percentage of CD4+ T cells,and the count of NK cells.did not show any signficant differences among the various age groups.The age-related changes observed in our study were as follow: 1) A decrease in the percentage of B cell; 2) A decrease in the counts of lymphcytes,T cells,B cells,CD4^+ T cells and CD8^+ T cells; 3)An increase in the percentage of NK cells; and 4)An increase in the CD4^+/CD8^+ ratio. Conclusions: A characheristic of the aging process show a marked decrease in T and B cells. The age-related increase in percentage of cells bearing NK markers can be interpreted as a compensatory consequence to cope with the deterioration of the immune system with age.(korean J Clin pathol 2001;21:135-40)

Why Don’t Cancer Survivors Quit Smoking? An Evaluation of Readiness for Smoking Cessation in Cancer Survivors

Melissa A. Little,Robert C. Klesges,Zoran Bursac,Jon O. Ebbert,Jennifer P. Halbert,Andrew N. Dunkle,Lauren Colvin,Patricia J. Goedecke,Benny Weksler 대한암예방학회 2018 Journal of cancer prevention Vol.23 No.1

Background: Cancer survivors have a high rate of participation in cigarette-smoking cessation programs but their smoking-abstinence rates remain low. In the current study, we evaluated the readiness to quit smoking in a cancer-survivor population. Methods: Cross-sectional data survey conducted among 112 adult cancer survivors who smoked cigarettes in Tennessee. Analyses were conducted using a two-sample t-test, χ2 test, Fishers Exact test, and multivariable logistic regression with smoker’s readiness to quit as the dependent variable. We operationally defined a smoker not ready to quit as anyone interested in quitting smoking beyond the next 6 months or longer (or not at all), as compared to those that are ready to quit within the next 6 months. Results: Thirty-three percent of participants displayed a readiness to quit smoking in the next 30 days. Smokers ready to quit were more likely to display high confidence in their ability to quit (OR = 4.6; 95% CI, 2.1-9.7; P < 0.0001) than those not ready to quit. Those ready to quit were nearly five times more likely to believe smoking contributed to their cancer diagnosis (OR = 4.9; 95% CI, 1.1-22.6; P = 0.0432). Those ready to quit were also much more likely to attempt smoking cessation when diagnosed with cancer (OR = 8.9; 95% CI, 1.8-44.3; P = 0.0076) than smokers not ready to quit. Finally, those ready to quit were more likely to endorse smoking more in the morning than other times of the day, compared to those not ready to quit (OR = 7.9; 95% CI, 1.5-42,3; P = 0.0148), which increased odds of readiness to quit within the next 6 months. Conclusions: Despite high participation in smoking-cessation programs for cancer survivors, only one-third of participants were ready to quit. Future research is needed to develop programs targeting effective strategies promoting smoking cessation among cancer survivors who are both ready and not ready to quit smoking. (J Cancer Prev 2018;23:44-50)

면역학적 노화 기전에 관한 연구: T 및 B 세포의 변화

김재식,이원길,서장수,송경은,이중원,이난영,Kim, Jay Sik,Lee, Won Kil,Suh, Jang Soo,Song, Kyung Eun,Lee, Joong Won,Lee, Nan Young,Weksler, Marc E. 대한면역학회 2001 Immune Network Vol.1 No.3

Background: An immunological approach for aging mechanism appears to be important. Lymphocyte subsets analysis in peripheral blood is widely performed to assess the immune status and to diagnose and monitor various diseases. Some lymphocyte subsets are known to change with age, but only few data about age-related reference ragnes for these subsets in healthy individuals have been reported. So we attempted to report reference ranges for these subsets in each age group and review changes of the results with age for the secondary studies about immune cell function as lymphocyte blast transformation and immunoglobulin gene rearrangement (VDJ) including recombination activating genes (RAG-1 and RAG-2). Methods: Lymphocyte subset analysis was performed on 302 subjects, 189 males and 113 females with age group of all decades of life. Two color direct immunofluorescene flow cytometry (FCM) was done using $Simultest^{TM}$ IMK-Lymphocyte kit (Becton Dickinson, USA), $FACScan^{TM}$ (Becton Dickinson, USA) and $FACSCalibur^{TM}$ (Becton Dickinson, USA). Lymphocyte subsets analysed were T ($CD3^+$) and B cells ($CD19^+$), helper/inducer T ($CD4^+$) and suppressor/cytotoxic T cells ($CD8^+$), helper/suppressor ($CD4^+/CD8^+$) ratio and natural killer (NK) cells ($CD3^-CD16^+/CD56^+$). The absolute numbers of each subset were calculated from total lymphocyte counts. Data collected was analysed using SAS 6.12. A P-value of < 0.05 was considered significant. Results: We reported the counts and percentages of lymphocyte and these subsets in each age group. There were no statistically significant differences between male and female subjects. The percentage of $CD4^+$ T cells, and the count of NK cells did not show the significant difference among the various age groups. The age-related changes observed in our study were as following: 1) a decrease in the percentages of T cells, B cells and $CD8^+$ T cells ; 2) a decrease in the counts of B cells and $CD8^+$ T cells ; 3) an increase in the percentage and count of NK cells ; and 4) an increase in the $CD4^+/CD8^+$ ratio. Conclusion: The characteristics of aging process appeared to be showing a marked decrease of lympocyte subsets T and B cells as well as T8 ($CD8^+$). The age-related increase of the percentage of cells bearing NK marker can be interpreted as a compensatory consequence to cope with the decrease of T cells related to the thymic involution. These changes with age appeared to be for the secondary study about immune cell function as lymphocyte blast transformation and immunoglobulin gene rearrangement.