• Journal of Chest Surgery
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• v.30 no.2
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• pp.164-171
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• 1997

Heart transplantation is now accepted as a definitive therapeutic modality in patients with terminal hear failure. The first successful heart transplantation in humans was done in 1967 and the first case in Korea was performed in november, 1992. Since the first case in 1992, more than 50 cases have been performed in Korea. A total of 20 patients underwent orthotopic heart transplantation since November, 1992 in Asan Medicla Center. The purpose of this study is to evaluate the early results and the follow-up course of 20 cases of heart transplantation done in Asan Medical Center. The average age of 20 patients was 39.9$\pm$11.8 years old(20~58). The mean follow-up duration was 14.4$\pm$11.2 months(1~41). All patients are alive till now. The blood type was identical in 14 and compatible in 6 patients. ihe original heart disease was dilated cardiomyopathy in 16, valvular heart disease in 2, ischemic cardiomyopathy in 1, and giant cell myocarditis in 1 patient. HLA cross matching for recipient and donor was done in 18 cases and the results were negative for T-cell and B-cell in 16 patients, pos tive for warm B-cell in 2 patients. Among 6 loci of A, B, and DR, one locus was matched in 8 cases, 2 loci in 5 cases, and 3 loci matched in 1 case. The number of acute allograft rejection averaged 2.8$\pm$0.5 (0~6) per case and the number of acute allograft rejection requiring treatment averaged 1.0$\pm$0.9 (1~3) per case. The time interval from operation to the first acute rejection requiring treatment was 35.5$\pm$20.4 days (5~60). Acute humoral rejection was suspected strongly in 1 case and was successfully treated. The left ventricular ejection fraction measured by echocardiography and/or MUGA scan was dramatically increased from 17.5$\pm$6.8 (9~32)% to 58.9$\pm$2.0 (55~62)% after heart transplantation. Temporary pacing was needed in 5 patients over 24 hours but normal sinus rhythm appeared within 7 days in all cases. One patient has been taken permanent pacemaker implantation due to complete AV block appearing 140 days after heart transplantaion. One patient had cyclosporine-associated n urotoxicity during the immediate postoperative period and was recovered after 27 hours. The heart transplantation of Asan Medical Center is on a developing stage but the early result is comparable to that of well established centers in other countries, even though the long-term follow-up result must be reevaluated. We can conclude that the heart transplantion is a promising therapeutic option in patients with terminal heart failure.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.497-509
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• 2002

Background : The mechanisms through which cellular activation results in intracellular mycobacterial killing is only partially understood. However, in vitro studies of human immunity to Mycobacterium tuberculosis have been largely modeled on the work reported by Crowle, which is complicated by several factors. The whole blood culture is simple and allows the simultaneous analysis of the relationship between bacterial killing and the effect of effector cells and humoral factors. In this study, we attempted to determine the extent to which M. tuberculosis is killed in a human whole blood culture and to explore the role of the host and microbial factor in this process. Methods : The PPD positive subject were compared to the umbilical cord blood and patients with tuberculosis, diabetes and lung cancer. The culture is performed using heparinized whole blood diluted with a culture medium and infected with a low number of M. avium or M. tuberculosis $H_{37}Ra$ for 4 days by rotating the culture in a $37^{\circ}C$, 5% $CO_2$ incubator. In some experiments, methlprednisolone- or pentoxifyline were used to inhibit the immune response. To assess the role of the T-cell subsets, CD4+, CD8+ T-cells or both were removed from the blood using magnetic beads. The ${\Delta}$ log killing ratio was defined using a CFU assay as the difference in the log number of viable organisms in the completed culture compared to the inoculum. Results : 1. A trend was noted toward the improved killing of mycobacteria in PPD+ subjects comparing to the umbilical cord blood but there was no specific difference in the patients with tuberculosis, diabetes and lung cancer. 2. Methylprednisolone and pentoxifyline adversely affected the killing in the PPD+ subjects umbilical cord blood and patients with tuberculosis. 3. The deletion of CD4+ or CD8+ T-lymphocytes adversely affected the killing of M. avium and M. tuberculosis $H_{37}Ra$ by PPD+ subjects. Deletion of both cell types had an additive effect, particularly in M. tuberculosis $H_{37}Ra$. 4. A significantly improved mycobacterial killing was noted after chemotherapy in patients with tuberculosis and the ${\Delta}$ logKR continuously decreased in a 3 and 4 days of whole blood culture. Conclusion : The in vitro bactericidal assay by human whole blood culture model was settled using a CFU assay. However, the host immunity to M. tuberculosis was not apparent in the human whole blood culture bactericidal assay, and patients with tuberculosis showed markedly improved bacterial killing after anti-tuberculous chemotherapy compared to before. The simplicity of a whole blood culture facilitates its inclusion in a clinical trial and it may have a potential role as a surrogate marker in a TB vaccine trial.

• Journal of Animal Science and Technology
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• v.48 no.6
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• pp.933-942
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• 2006

This experiment was carried out to investigate effects of honeybee venom treatment on the humoral immune response in pigs. Corresponding author : S. K. Cho, Dept. of Animal Sci. Chung-Buk National University, Kaesin-dong, Cheongju, 361-763, Korea. phone : 043-261-2551. E-mail : deercho@chungbuk.ac.kr To investigate effects of natural honeybee venom on the concentration of immunoglobulin G, A, and M, 20 piglets(LY×D) from 3 sows were allocated into two groups bee venom-treated group(10 piglets) and non-treated control(10 piglets). Natural honeybee venom was treated at 0, 3, 6 days after birth and the acupoints were Hai-men(ST-25), Du-kou(CV-8) and Jiao-chao(GV-1) points at 0, 3 days after birth and the regions of castration and tail amputation point at 6 days. Control group was injected 1㎖ of saline to the same site. Concentrations of IgG, A, and M were measured with immunoturbidimetric method at 0, 3, 7, 14, and 21 days after treatment. To investigate the effect of bee venom on the production of antibodies against hog cholera and atrophic rhinitis vaccines that were used as indicator antigens, 40 piglets(LYxD) from 5 sows were grouped as bee venom-treated group (20 piglets) and control group(20 piglets). Natural honeybee venom was treated at 0, 3days(castration, tail amputation) and 21days after birth. The acupoints were Hai-men(ST-25), Du-kou(CV-8) and Jiao-chao (GV-1) points at 0 day, the regions of castration and tail ampution at 3 days and Jiao-chao(GV-1) and Bai-hui(GV-20) points at 21days after birth(weaning). Control group was injected 1ml of saline to the same site. Atrophic rhinitis vaccine was injected twice at 24 and 44 days after birth and hog cholera vaccine was also injected twice at 44 and 64 days after birth. Antibody titers against Bordetella bronchiseptica and hog cholera virus were measured by using tube agglutination and ELISA tests at 24, 34, 44, 54 and 74 days after birth. Concentrations of IgG of treated group were 339.52, 366.48, 296.52, 242.06 and 219.06mg/dl at 0, 3, 7, 14 and 21 days after birth, respectively. In contrast, concentrations of IgG in control group were respectively 347.10, 334.14, 243.28, 205.18 and 191.58mg/dl during same periods with treated group. Concentrations of IgG at 0 day was not significantly different between the treated group and control group but treated group were significantly increased by 10.28% at 3 days after birth (P<0.02), 21.88% at 7 days after birth(P<0.01), 18.0% at 14 days after birth(P<0.07) and 14.3% at 21 days after birth(P<0.01). Concentrations of IgA and Ig M were not significantly different. Antibody titers against hog cholera virus were significantly increased by 57.0% at 24 days after birth(P<0.03), 74.6% at 34 days after birth (P<0.006), 48.6% at 44 days after birth(P<0.017), 45.0% at 54 days after birth(P<0.16) and 44.4% at 74 days after birth (P<0.006) in bee venom treated group in comparison with control group. Antibody titers against the Bordetella bronchiseptica was significantly increased in Beevenom treated group as 9.1% (P<0.32) at 24days, 39.7% (P<0.002) at 34days, 31.9% (P<0.02) at 44days, 33.4% (P<0.01) at 54days and 57.3% (P<0.007) at 74 days after birth when compared with those of control group pigs. Collecting together, the results in this study showed that immune responses were increased by treatment of natural honeybee venom to pigs. These results suggested that the treatment of bee venom could be used effectively for the increase of productivity in livestock industry.

• Biomedical Science Letters
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• v.2 no.2
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• pp.133-151
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• 1996

After cardiac surgery, it has been recognized that various complications were associated with injured humoral and cellular immunity by cardiopulmonary bypass(CPB). Especially, in postoperative pulmonary dysfunction, transpulmonary leukostasis followed complement activation and inflammatory responses are major pathogen. Some studies have showed that pretreated-corticosteroids before CPB protected postoperative pulmonary dysfunction. Corticosteroids may inhibit complement and leukocyte activation. On based previous studies, present investigator determined changes of leukocyte counts and transpulmonary leukostasis during cardiac surgery and postoperative periods. For the evaluation of postoperative pulmonary function and edema, $PaO_2$ and chest X-ray were compared between pre-CPB and post-CPB. Fever and other parameters were also observed postoperatively. The aim of this study was to define for the prophylactic effects of corticosteroid(Solu-Medrol: 30mg/kg) on all the researched parameters. This study was prospectively designed with randomized-blind fashion for 50 patients undergoing cardiac surgery. According to the purpose of study, all patients were divided into placebo and steroid group. : Placebo group was 25 patients received normal saline(not corticosteroid), and steroid group was 25patients received corticosteroid(Solu-Medrol: 30mg/kg) before initiation of CPB. The results of study were summarized as follows. 1. Total peripheral leukocyte counts decreased significantly at 5 minutes of CPB in all patients(P<0.01), and began to increase progressively at later periods of CPB with neutrophilia. The significant rise remained at postoperative 7th day(P<0.05). 2. During partial CPB, transpulmonary leukostasis occurred in placebo group(P<0.001), whereas it was prevented in steroid group. 3. In both groups, peripheral lymphocyte counts were stable during CPB, but began to reduce at time of intensive care unit(ICU) and the lymphocytopenia remained until postoperative 3rd day. The lymphocyte counts recovered on postoperative 7th day. 4. In both groups, peripheral counts of monocyte were relatively stable in the early peroid of CPB, and increased gradually in the later periods of CPB. This significant monocytosis remained throughout postoperlative periods(P<0.05). 5. The mean value of postoperative $paO)_2$ was lower than that of pre-CPB in placebo group(P=0.01) but didn't significant in steroid group(P=0.90). In the incidence of pulmonary edema signs and fever, placebo group was higher than steroid group(P=0.001, p=0.01, respectively). However mechanical respiratory supporting and care periods at intensive care unit were not significant difference between two groups(P>.0.05).With the above results, the investigator concluded that leukocyte activation and pulmonary sequestration were caused by cardiac surgery with CPB and demonstrated that high dose corticosteroid will provide prophylactic effect for pulmonary leukostasis and higher neutrophilia. These effects may ameliorate postoperative pulmonary dysfunction and contribute to postoperative less morbidity. However, further study should be performed because postoperative lymphocytopenia continued for 3 days in both groups, which may suspected damage or suppression of cell-mediated immunity with used corticosteroid.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.855-861
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• 1995

Background: Parathyroid hormone-related protein(PTHrp) was first identified as the cause of hypercalcemia in malignancy. Hypercalcemia can be found in malignancy, especially in the epidermoid carcinoma of the lung, even without extensive metastases to the bones. The application of sensitive assays for PTHrp may help in the early diagnosis of lung cancer, in the monitoring of treatment and in the detection of recurrence. Method: Serum PTHrp was measured by radioimmunoassay detecting the N-terminal 1~34 peptide of human PTHrp(PTHrp 1-34) in 63 histologically confirmed lung cancer patients and 22 healthy controls. Result: Serum PTHrp(mean$\pm$S.E.) was $312{\pm}68.9pg/ml$ in 63 lung cancer patients and $158{\pm}38.2pg/ml$ in 22 controls(p>0.05). PTHrp was $356{\pm}103.9pg/ml$ in 34 epidermoid carcinoma patients, $281{\pm}148.7pg/ml$ in 15 adenocarcinoma patients and $316{\pm}140.8pg/ml$ in 9 small cell carcinoma patients. In epidermoid carcinoma patients, PTHrp was $570{\pm}472.3pg/ml$ in stage II(n=3; p<0.05 vs controls), $166{\pm}22.4pg/ml$ in stage IIIa(n=9), $282{\pm}113.3pg/ml$ in stage IIIb(n=12) and $668{\pm}367.9pg/ml$ in stage IV(n=9; p<0.05 vs controls). PTHrp was significantly increased in 8 epidermoid carcinoma patients with bone metastases($1526{\pm}811.2\;pg/ml$; p<0.0005 vs controls). Hypercalcemia was observed in an epidermoid carcinoma patient whose PTHrp value was 244 pg/ml. Conclusion: The serum PTHrp was increased in advanced epidermoid carcinoma patients even without hypercalcemia. The measurement of PTHrp may be not helpful in the early diagnosis of lung cancer. But the lung cancer should be suspected in the marked elevation of PTHrp. It may be of value in detecting patients of advanced diseases with bone metastases or patients who might develop the malignancy associated hypercalcemia.

• Journal of Chest Surgery
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• v.29 no.11
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• pp.1173-1181
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• 1996

The causes of degenerative changes in allograft cardiac valves are not well known to this day. Today's preserved allografts possess highly viable endothelial cells and degeneration of allografts can be facilitated by immune reaction which may be mediated by these viable cells. To test the antigenicity of endothelial cells, pieces from aortic wall were obtained from fresh and cryo-preserved rat allograft. Timings of sampling were prior to sterilization, after sterilization, after 1, 2, 7, 14 days of fresh preservation and cryopreservation. Endothelial cells were tested by immunohistochemical methods using monoclonal antibodies to MHC class I(MRC OX-18), class II(MRC OX-6) and ICAM-1 antigens. After transplantation of each group of aortic allograft at the subcutaneous layers of rats, population of CD4$^{+}$ T cell and CD8$^{+}$ T cell were analyzed with monoclonal antibodies after 1, 2, 3, 4, 6 and 8 weeks. MHC class I expression was 23.95% before preservation and increased to 35.53~48.08% after preservation(p=0.0183). MHC Class II expression was 9.72% before preservation and 10.13~13.39% after preservation(P=0.1599). ICAM-1 expression was 15.02% before preservation and increased to 19.85~35.33% after preservation(P=0.001). The proportion of CD4$^{+}$ T-cell was 42.13% before transplantation. And this was 49.23~36.8% after transplantation in No treat group (p=0.955), decreased to 29.56~32.80% in other group(p=0.0001~0.008). In all the groups, the proportion of CD8$^{+}$ T-cell increased from 25.57% before transplantation to 42.32~58.92% after transplantation(p=0.000l~0.0002). The CD4$^{+}$/CD8$^{+}$ ratio decreased from 1.22~2.28 at first week to 0.47~0.95 at eighth week(p=0.0001). The results revealed that the expression of MHC class I and ICAM-1 in aortic allograft endothelium were increased but that of MHC class II were not changed, despite the different method of preservation. During 8 weeks after transplantation of aortic allograft, the subpopulations of CD4$^{+}$ T cell were not changed or only slightly decreased but those of CD8$^{+}$ T cell were progressively increased.ely increased.

• Parasites, Hosts and Diseases
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• v.29 no.3
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• pp.279-292
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• 1991

The immune response to sheep red blood cell (sRBC) was monitored in the mice infected with Ascaris strum or Trichinella spiralis. The effects of the infection with T. spiralis or the injection with cyclophosphamide (CY) as an immunosuppression agent prior to challenge infection with the embryonated eggs of A. suum were monitored in mice by means of the level of infection with A. strum and cellular and humoral immune response to sRBC. following the oral administration of 1, 000 eggs of A. suum to mice, delayed-type hypersensitivity (DTH) and rosette-forming rate were gradually decreased and reached to the lowest levels at the 5th week and 6th week postinfection, respectively, and then returned to normal at the loth week. The hemagglutinin (HA) and hemolysin (HE) titers were gradually elevated and reached to peak at the 3rd week postinfection, and then returned to normal level. The appearance ratios of the eosinophils and mast cells were in peak at the 4th week and the 2nd week postinfection, respectively. Meanwhile the harvest ratio of A. suum larvae from the liver and lungs was 21.97% at the 1st week postinfection. Following the oral administration of 300 T. spiralis infective larvae, DTH and rosette-forming rate were gradually decreased with the lapse of time and reached the lowest values in the 30th and 21st day of postinfection, and then slightly increased and transiently decreased in the 70th and 80th day of postinfection, respectively. HA and HE titers were the lowest in the 21st and 90th day, whereas the ratios of eosinophils and mast cells were the highest on the 40th and 14th day posti nfecti on, ruts petit i vela. Following the intraperitoneal injection of CY, the body weight, the spleen weight, DTH, rosette-orming ratio, HA and HE titers, the number of WBC and the ratio of the mast cell were predominantly decreased in the 5th day, and then returned to the same value of the 1st day postinjection. The ratio of eosinophils was gradually decreased following to advance of days. At the 1st, 5th and loth days after intraperitoneal injection of CY of 400 mg/kg, a dose with 1, 000 eggs of A. suum was administered orally to mice, and harvest rate of the larvae at the 7th day postadministration was 7.07% in the 1st day, 14.94% in the 5th day, 10.1% in the loth day, 8.02% in control group. The effect of prior infection with infective larvae of T. spiralis upon immunological sequelae of a challenge infection of mice with embryonated eggs of A. suum in 30 or 70 days interval was checked. On the 37th day of prior infection with T. spiralis, that was the 7th day with A. suum postinfection, DTH and rosette-forming rate were drastically decreased, but the ratio of mast cells was highly increased and the ratio of eosinophils, HA and HE titers were fairly increased. On the other hand, the rate of larvae harvest was 9.3% in experimental group in contrast with 22.18% in control group. Meanwhile the effect of immune response to sRBC was similar to that of the former, but DTH and rosettt-forming rate were greatly decreased in the 77th day after prior infection with the 7th day after challenge infection in compariton with control. At that time, Ascaris larvae were harvested 8.3% in experimental group in comparison with 10.5% in control group.

• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.247-268
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• 1996

It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.