Diagnostic value of peripheral blood immune profiling in colorectal cancer

PURPOSE: Little is known about the clinical value of peripheral blood immune profiling. Here, we aimed to identify colorectal cancer (CRC)-related peripheral blood immune cells and develop liquid biopsy-based immune profiling models for CRC diagnosis. METHODS: Peripheral blood from 131 preoperative patients with CRC and 174 healthy controls was analyzed by flow cytometry and automated hematology. CRC-related immune factors were identified by comparing the mean values of immune cell percentages and counts. Subsequently, CRC diagnostic algorithms were constructed using binary logistic regression. RESULTS: Significant differences were observed in percentages and counts of white blood cells, lymphocytes, neutrophils, regulatory T cells, and myeloid-derived suppressor cells (MDSCs) of patients and controls. The neutrophil/lymphocyte and Th1/Th2 ratios were also significantly different. Likewise, the percentages and counts of peripheral blood programed death 1, cytotoxic T lymphocyte antigen 4, B-and T-lymphocyte attenuator, and lymphocyte activation gene-3 were higher in patients with CRC. The binary logistic regression model included 12 variables, age, CD3+%, NK%, CD4+CD279+%, CD4+CD25+%, CD4+CD152+%, CD3+CD366+%, CD3+CD272+%, CD3+CD223+%, CD158b−CD314+CD3−CD56+%, Th2%, and MDSCs cells/µL, for the prediction of cancer. Results of retrospective and prospective evaluation of the area under the curve, sensitivity, and specificity were 0.980 and 0.940, 91.53% and 85.80%, and 93.50% and 86.20%, respectively. CONCLUSION: Peripheral blood immune profiling may be valuable in evaluating the immunity of CRC patients. Our liquid biopsy-based immune diagnostic method and its algorithms may serve as a novel tool for CRC diagnosis. Future largescale studies are needed for better characterization of its diagnostic value and potential for clinical application.

Relationships between Nutrient Intake Status and Sugar-containing Food Intake of Elementary School Students in Daegu-Kyungbook Area / 대한지역사회영양학회지

This study was conducted to investigate the association of nutrients intake with sugar-containing food consumption of elementary school students in Daegu-Kyungpook area. We analyzed the dietary information from 164 elementary school students (82 boys, 82 girls) participated in "Dietary Intake Survey of Infants, Children and Adolescents" conducted by Korea Food & Drug Administration and Korea Health Industry Development Institute. Information on habitual dietary intake of sugar-containing foods was collected by food frequency questionnaires. Daily nutrients intake of each subject was calculated from 24-hour recall data for two non-consecutive days. As a result of average daily intake of major foods of elementary school students was analyzed from 1 to 50 ranking that show up higher ranking of white milk and white rice but include many kind of sugar-containing food. Dietary intake of energy, carbohydrate, Ca, P, Fe and riboflavin were significantly lower for girls with higher sugar-containing food frequency scores. Significantly negative associations between Index of Nutrition Quality (INQ) and sugar-containing food frequency scores were observed for calcium (r = -0.34) and iron (r = -0.32) among girls. Mean Adequacy Ratio (MAR) was significantly lower for girls with higher sugar-containing food frequency scores (r = -0.26). Our results indicated that nutrition education for elementary school students should focus on the importance of reducing the sugar-containing food consumption with more attention for girls.

Nutritional Status of Zinc and Copper in Type 2 Diabetic Patients after Short-term Zinc Supplementation / 대한지역사회영양학회지

This study was carried out to determine whether a short-term zinc supplementation could improve the zinc status without adverse changes in copper status among type 2 diabetic patients. Seventy-six diabetic subjects and 72 normal adults participated in this study. Subjects were randomly divided into supplemented and control groups. Forty-four diabetic patients and 34 normal subjects were supplemented with 50 mg zinc gluconate daily for 4 weeks. Dietary intakes of participants were measured for two non-consecutive days by 24-hour recall method. Nutritional status of zinc and copper were also evaluated by biochemical measurement of fasting plasma samples and spot urinary collection. At baseline, diabetic patients showed significantly lower levels of dietary zinc intake and higher urinary zinc excretion than the normal adult group (P < 0.05, P < 0.0001). Plasma level of zinc was not significantly different between diabetic and normal adults at baseline. However, plasma zinc level increased significantly in both diabetic patients and normal adults after zinc supplementation. The changes in plasma copper levels following zinc supplementation were not statistically significant in diabetic subjects as well as in normal adults. These results indicated that four weeks of zinc supplementation did not influence Cu status and that it may contribute to improving the zinc status. Therefore, we suggest that Zn supplementation for a short-term period may improve marginal zinc status of diabetic patients without interfering with their copper status

ICAM-1/LFA-1 interaction contributes to the induction of endothelial cell-cell separation: implication for enhanced leukocyte diapedesis

The basic route and mechanism for diapedesis has not yet to be fully defined. Here we present evidence that "cell-cell separation" between endothelial cells (ECs) may provide a route for leukocyte diapedesis. We unexpectedly found that extensive interaction between peripheral blood leukocytes and ECs that were activated by TNF-alpha induced the opening of EC contacts and, surprisingly, resulted in cell-cell separation. This event was specific to the intercellular adhesion molecules-1 (ICAM-1)/leukocyte function-associated antigen-1 interaction, as demonstrated by the following: (1) ICAM-1 expression correlated with increased EC contraction; and (2) the blocking of ICAM-1 selectively inhibited EC separation. Thus, we suggest that "cell-cell separation" could be a mechanism for diapedesis in situations that may require massive leukocyte infiltration.

ICAM-1/LFA-1 interaction contributes to the induction of endothelial cell-cell separation: implication for enhanced leukocyte diapedesis

The basic route and mechanism for diapedesis has not yet to be fully defined. Here we present evidence that "cell-cell separation" between endothelial cells (ECs) may provide a route for leukocyte diapedesis. We unexpectedly found that extensive interaction between peripheral blood leukocytes and ECs that were activated by TNF-alpha induced the opening of EC contacts and, surprisingly, resulted in cell-cell separation. This event was specific to the intercellular adhesion molecules-1 (ICAM-1)/leukocyte function-associated antigen-1 interaction, as demonstrated by the following: (1) ICAM-1 expression correlated with increased EC contraction; and (2) the blocking of ICAM-1 selectively inhibited EC separation. Thus, we suggest that "cell-cell separation" could be a mechanism for diapedesis in situations that may require massive leukocyte infiltration.

Vitamin A and Vitamin E Status of Diabetic Patients and Normal Adults in Korea

We evaluated the vitamin A and E status of type 2 diabetic patients and normal adults living in Daegu area. Dietary intakes for two non-consecutive days were measured by 24-hour recall method for 76 diabetic patients and 72 normal adults. Plasma levels of retinol and alpha-tocopherol were measured using HPLC method. Dietary intakes of vitamin A were not significantly different between the diabetic and the normal adults. However, the diabetic patients had significantly lower vitamin E intakes than the normal adults. Major food sources for vitamin A intake were red pepper powder and carrot. Half of the subjects from diabetic as well as normal adults consumed less than estimated average requirement of vitamin A. Plasma levels of retinol and tocopherol were maintained within normal ranges for most of the subjects regardless of diabetic status. Dietary intake of vitamin A was associated with vitamin E intake, however, there was no significant correlations between vitamin E intake and plasma alpha-tocopherol levels. It seems that diabetic patients should try to increase dietary intake of vitamin E, as prolonged lower-level intake of vitamin E could eventually lead to vitamin E depletion. Further studies are needed to identify the magnitude of dietary variance at individual and seasonal levels, and to understand the discrepancies in dietary intake and plasma levels before establishing the dietary reference intake based on Korean dietary pattern.

Glycemic control of type 2 diabetic patients after short-term zinc supplementation

This study was carried out to determine whether a short-term zinc supplementation contributes to beneficial changes in glycemic control among type 2 diabetic patients. Seventy-six diabetic subjects and 72 normal adults participated in this study. Subjects were divided into supplemented and control groups. Forty-four diabetic patients and 34 normal subjects were supplemented with 50 mg zinc daily as zinc gluconate for 4 weeks. Zinc status was assessed from fasting plasma levels and urinary excretion. The effects of zinc supplementation on fasting blood glucose, HbA1c, insulin, and C-peptide were measured at the beginning of the study and after 4 weeks of supplementation. The changes in glycemic control indicators were compared between diabetic groups, classified by baseline HbA1c levels, and by diabetic duration. At baseline, the incidence of marginal zinc deficiency in the diabetic group, as determined by plasma zinc level, was approximately twice as high as in the normal adult group. The changes of HbA1c concentration, and fasting blood glucose following supplementation were not statistically significant in diabetic subjects. In normal subjects, a significant decrease of HbA1c occurred only in the zinc supplemented group. No significant changes were observed for serum insulin and C-peptide in diabetic as well as normal subjects. However, when the changes were compared by baseline HbA1c level, we found that diabetic subjects with HbA1c > or = 7.5% showed significantly improved levels of HbA1c and fasting glucose after Zn supplementation. While such improvement in fasting blood glucose was significant among diabetics with shorter diabetic duration, significant levels of increase in serum insulin and C-peptide were observed in zinc supplemented subjects with longer diabetic duration. Fasting blood glucose was significantly decreased, whereas serum insulin and C-peptide were increased in diabetics with marginal zinc status. Therefore, we suggest that Zn supplementation for a short-term period may improve glycemic control in diabetic patients with higher HbA1c levels and marginal zinc status.

Cytoplasmic Domain of Intercellular Adhesion Molecule-1(ICAM-1)is Important for the ICAM-1 Mediated Membrane Projection of Endothelial Cells / 대한해부학회지

Intercellular adhesion molecule-1 (ICAM-1)has been shown to enhance leukocyte adhesion, thereby inducing migration through blood endothelial cells. However, the molecular event during the process of adhesion is largely unknown. To examine the role of ICAM-1 cytoplasmic domain in SDF-1 alpha-induced T lymphocyte migration and adhesion, mutant human ICAM-1 molecules were expressed in COS-7 cell line. COS-7 cells expressing ICAM-1_GFP mutant without alpha-actinin revealed no association with the actin cytoskeleton, while wild-type ICAM-showed clear association with the actin, as observed by confocal microscopy, suggesting that actinin binding motif in the cytoplasmic domain of ICAM-1 is important for the proper localization of ICAM-1 on the cell membrane. However, based on adhesion assay, we found that the cytoplasmic domain of ICAM-1 is not essential for the binding of lymphocytes which were activated by SDF-1alpha. On the other hand, ICAM-1-mediated receptor-ligand clustering event was significantly inhibited in the cells expressing ICAM-1 mutants without alpha-actinin or whole cytoplasmic domain. Taken together, these results suggest that ICAM-1 cytoplasmic domain is not essential for the adhesion but important for the ligand-receptor-mediated membrane projection of endothelial cells before trans-endothelial migration of lymphocytes.

Soluble factor from tumor cells induces heme oxygenase-1 by a nitric oxide-independent mechanism in murine peritoneal macrophages

Tumor target-derived soluble secretary factor has been known to influence macrophage activation to induce nitric oxide (NO) production. Since heme oxigenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress, we questioned whether soluble factor from tumor cells induces HO-1 through NO-dependent mechanism in macrophages. We designated this factor as a tumor-derived macrophage-activating factor (TMAF), because of its ability to activate macrophages to induce iNOS. Although TMAF alone showed modest activity, TMAF in combination with IFN-gamma significantly induced iNOS expression and NO synthesis. Simultaneously, TMAF induced HO-1 and this induction was slightly augmented by IFN-gamma. Surprisingly, however, induction of HO-1 by TMAF was not inhibited by the treatment with the highly selective iNOS inhibitor, 1400 W, indicating that TMAF induces the HO-1 enzyme by a NO-independent mechanism. While rIFN-gamma alone induced iNOS, it had no effect on HO-1 induction by itself. Collectively, the current study reveals that soluble factor from tumor target cells induces HO-1 enzyme in macrophages. However, overall biological significance of this phenomenon remains to be determined.

The Function of Dimeric Structure of Soluble Intercellular Adhesion Molecule - 1 ( sICAM-1 ): Inhibition of Leukocyte Function Associated Antigen - 1 ( LFA-1 ) Binding to ICAM-3

Intercellular adhesion molecule-1 (ICAM-1) is a membrane protein, exists as a dimer on the cell surface, and interacts with leukocyte function associated antigen-1 (LFA-1), a member of beta2-integrin family. A soluble circulating form of ICAM-1 (sICAM-1) is also detected in human serum, and has been implicated as a regulator for LFA-1-dependent cell-cell interaction in vivo. However, previous reports demonstrated that sICAM-1 shows little inhibitory effect on LFA-1 binding to ICAM-l, indicating that sICAM-1 is unlikely to antagonize LFA-1/ICAM-1-mediated cellular events in vivo. Here, we investigated the property of the dimeric sICAM-1 as an inhibitor of LFA-1 interaction with ICAM-3, since the lower avidity of LFA-1 for ICAM-3 compared with ICAM-1 or ICAM-2 had been speculated. Using recently constructed heterodimeric sICAM-1 joined at the C terminus via an a-helical coiled coil (ACID-BASE) (Jun, CD. et al., 2001, Proc Natl Acad Sci 98, 6830-6835), we also tested whether the structural integrity in dimer could affect the inhibitory action of sICAM-1. Engineered sICAM-1 dimer that contained intact ectodomain (E34/E34) significantly blocked SKW3 cell (LFA-1+) binding to ICAM-3, but not to ICAM-1 and ICAM-2, indicating the lower avidity of LFA-1 to ICAM-3 than that of both ICAM-1 and ICAM-2. A one binding site knock out mutant (E34/K34) showed -2-fold reduction in efficiency compared with E34/E34 to inhibit cell binding. Interestingly, a one binding domain deletion mutant (E34/deltaD1-D2) showed significant reduction (~5-fold) compare with E34/K34, suggesting that structural integrity, which is precluded in E34/deltaD1-D2, is necessary for optimal binding of dimeric sICAM-1 to LFA-1, thereby inhibiting LFA-1/ICAM-3-dependent adhesion. Furthermore, BIAcore affinity measurements revealed that E34/deltaD1-D2 bound to immobilized soluble open LFA-1 I domain with an -3-fold reduced affinity compared with E34/K34. Overall, our results demonstrate that maintaining the structural integrity in dimer is necessary for optimal binding of sICAM-1 to LFA-1, and further suggest the therapeutic potential of dimeric sICAM-1 to antagonize LFA-1/ICAM-3-mediated cellular events in vivo.

The Effect of Individualized Nutritional Education on Adults having two or more Symptoms of Chronic Degenerative Disease / 대한지역사회영양학회지

This study was intended to evaluate the overall effects of nutritional education on adults having two or more symptoms of chronic degenerative disease. A nine week nutritional education program was provided for 65 adults with chronic diseases. We assessed the changes in dietary knowledge, eating behavior and socio-psychological factors. When we evaluated the nutrient intakes of the subjects, their energy intake was 79.4% of the Korean Recommended Dietary Allowances (RDA). Their dietary intake of other nutrients was also below the RDA level except for Vitamin C. Their knowledge of dietary therapy was slightly improved after the implementing of nutritional education. The dietary behavior of 'night snacks before sleep' was significantly improved. While the overall fear due to disease was significantly increased, self-efficacy was not improved. Self-efficacy for eating "three regular meals" and "choosing fruit, vegetable and grain" were significantly decreased. Family support for "buying food which is good for my health" was also significantly increased, whereas "advises me to eat appropriate foods for health" was decreased. Biochemical analysis indicated that blood levels of triglyceride, cholesterol and blood pressure improved after nutrition education. Therefore, we concluded that nutritional education program for people with chronic degenerative diseases could change the diet therapy knowledge, dietary behavior, and the fear due to disease, support from family and behavior intention toward the direction to improve the chronic disease condition. However, it did not improve self-efficacy. Our study also indicated that nutritional education strategies to improve self-efficacy should be an important aspect in a long term education plan for patients to establish desirable eating habits.

Health and Nutritional Status of Industrial Workers / 대한지역사회영양학회지

The study was curried out to collect information to establish a framework for nutrition education for the prevention of chronic degenerative disease. We analyzed differences in diet quality, food habits and health status of workers by work condition. Anthrometric parameters of height, weight and body fat were measured and biochemical parameters including glucose, total cholesterol, GOT, GPT and hemoglobin were determinded for 194 subjects. To assess the nutrient intake and diet quality of workers, dietary intake was measured by the day 24-hour recall method, Average daily nutrient intake, except for phos-phorous and vitamin C was lower than Korean RDA. The obesity related behavior score was significantly better in laborers than in office workers, while chronic degenerative diseases related to food habit score was significantly better in laborers than in office workers, while chronic degenerative diseases related to the food habit score was beet in offices workers than in laborers. Blood pressure, blood glucose levels were significantly higher in laborer than in office workers. Dietary variety score (DVS) food composition group score(FCGS), mean adequacy ratio(MAR) of office worker were better than those of labor workers. When diet quality was evaluated by FCGS(food composition group score) 16.0% of the subjects acquired 5 points and 14.4% of the subjects acquired 2 points. MAR and INQ showed a significantly positive correlation with DVS and FCGS . This results indicated that the onset possibility of hypertension and diabetes mellitus among chronic degenerative disease was higher in laborers than in office workers, while the onset possibility of obesity was higher in office workers than in laborers. In conclusion the overall diet quality of office workers is betters than that of laborers, therefore, nutrition education for prevention of chronic degenerative disease of industrial workers needs to be more focused on the improvement of the health status of laborers.

Zine Status of Adult Female in the Taegu Region as Assessed by Dietary Intake and Urinary Excretion / 대한지역사회영양학회지

This study was intended to examine the zinc status of free-living adult women living in the Taegu region. Zine intake of 102 female subjects was measured by food frequency method for 3 consecutive days. Urinary zine was assessed from urine samples collected fir twenty four hours. Average dietary zinc intake of adult female subjects using food record was 5.9+/-1.8 mg which was 49% of Korean RDA. When zine intake by frequency method was higher than by food record. Average urinary zine intake by frequency method was higher than that by food record. Thus, it appeared that zinc intake by frequency method was higher than that by food record. Average urinary zinc excretion of 102 adult female subjects was 0.28+/-0.16 mg, which belonged to marginal zinc deficiency range. Fifty nine of 102 subjects showed marginal zinc deficiency as assessed by urinary zinc excretion. If we compare the zinc status of adult female subjects by age group, zinc intake in the 50s was significantly higher than any other age groups. However, there were no significant differences in zinc status according to BMI groups and BMI groups. Significant correlations were found between zinc intake and energy, protein, carbohydrate and fat intake. Based on dietary zinc intake and urinary zinc, we concluded that zinc status of adult female living in the Taegu region is marginally deficient.