Results of Questionnaire Survey of Current Immune Monitoring Practice of Transplant Clinicians and Clinical Pathologists in Korea: Basis for Establishment of Harmonized Immune Monitoring Guidelines / 대한이식학회지

Detection of significant alloimmune response, which affects graft function and survival by effective immune monitoring, is critical for treatment decision making. However, there is no consensus regarding immune monitoring (IM) for kidney transplantation (flow KT) in Korea. The IM protocol may be affected by the level of immunological risk, the methods of desensitization and the availabilities of resources such as laboratory support and cost of tests. Questionnaire surveys designed to identify the current practices regarding immune monitoring of KT among transplant clinicians and clinical pathologists in Korea and eventually provide a basis for the establishment of harmonized immune monitoring guidelines in KT were administered as part of a Korean Society for Transplantation Sponsored Research Project. The survey results revealed significant variations in IM protocols and interpretation of tests affecting treatment decisions between institutes. Moreover, the results revealed a need to expand the histocompatibility tests into high resolution HLA typing in multiple loci and non-HLA antibody tests that facilitate the epitope analysis and eventually virtual crossmatching. The results of the questionnaire survey from clinical pathologists are addressing the urgent need for the standardization of interpretation and harmonization of results reporting in single antigen bead based HLA antibody identification. Finally, communication between clinicians and clinical pathologists to meet the clinical expectations regarding various immune monitoring tests is needed.

A Case of Behcet's Disease Associated with Schizophrenia and Myelodysplastic Syndrome with Trisomy 8 and 9

Behcet's disease (BD) is a multi-systemic inflammatory disease of unknown origin that affects nearly all organs. Recent reports of BD with myelodysplastic syndrome (MDS) often note an association with gastrointestinal involvement and trisomy 8. We herein report on a case of a 51-year-old man who had refractory schizophrenia and developed gastrointestinal BD and MDS with trisomy 8 and 9. He visited our hospital due to fever and abdominal pain. Multiple ulcerations in the colorectum were observed on colonoscopy, and he was diagnosed with intestinal BD. During the treatment of intestinal BD, anemia and thrombocytopenia developed. His bone marrow study revealed myelodysplastic syndrome (refractory anemia with ringed sideroblast) with trisomy 8 and trisomy 9. We report a rare case of intestinal BD accompanied by schizophrenia and myelodysplastic syndrome with trisomy 8 and 9.

Evaluation of Optimal Combination of Commercially Available Superparamagnetic Iron Oxide Nanoparticles and Transfection Agents for Labelling of Human Mesenchymal Stem Cells

PURPOSE: To determine the optimal combination of commercially available superparamagnetic iron oxide (SPIO) nanoparticles with transfection agents (TA). MATERIALS AND METHODS: Protamine sulfate (Pro) and poly-L-lysin (PLL) were incubated with ferumoxide and ferucarbotran in human mesenchymal stem cells at various concentrations, and cellular viability were evaluated. Cellular iron uptake was qualitatively and quantitatively evaluated. Cell visibility was assessed via MR imaging and the T2-relaxation time was calculated. RESULTS: The cellular viabilities with ferucarbotran were more significantly decreased than those with ferumoxide (p < 0.05). Iron uptake with ferumoxide was significantly higher than that for those with with ferucarbotran. The T2-relaxation time was observed to be shorter with ferumoxide in comparison to those with ferucarbotran (p < 0.05). Ferumoxide at a concentration of 25 microg/ml in combination with either Pro or PLL at a concentration of 3.0 microg/ml did not adversely impact cell viability, maximized iron uptake, and exhibited a lower T2-relaxation time in comparison to other combinations. CONCLUSION: Stem cells with ferumoxide exhibited a higher cellular viability and iron uptake in comparison to ferucarbotran- treated stem cells. A 25 microg/ml of ferumoxide with a 3.0 microg/ml of TA is sufficient to label mesenchymal stem cells.

Guillain-Barre Syndrome in a Patient with Chemotherapy for HIV Related Burkitt's Lymphoma

Human immunodeficiency virus infection is not a common cause of Guillain-Barre syndrome. Guillain-Barre syndrome with cerebrospinal fluid pleocytosis has been associated with early human immunodeficiency virus (HIV) infection, occasionally as the presenting manifestation. We report a case of 73-year-old Korean malen with acute motor axonal variant of Guillain-Barre syndrome during chemotherapy for HIV- related Burkitt's lymphoma. This is the first report of Guillain-Barre syndrome occurringed within HIV infection in Korea.

Needs for Hepatitis A Virus Immunization in Healthcare Personnel / 병원감염관리

BACKGROUND: Currently, the incidence of hepatitis A is on the increase in Korea. Although there is emphasis on contact precautions, the nosocomial outbreak of hepatitis A virus (HAV) in healthcare personnel has increased within endemic areas because these workers inevitably come in close contact with patients and work under suboptimal hygiene conditions. In this study, we evaluated the necessity of immunization against HAV for healthcare personnel. METHODS: We investigated the seropositivity of serum immunoglobulin G (IgG) anti-HAV antibody (Ab) in 672 healthcare personnel on the basis of their age-group, sex, and occupation in Soon Chun Hyang University Hospital and Soon Chun Hyang University Bucheon Hospital. RESULTS: The subjects were divided into 6 groups on the basis of their ages to identify differences among the various age groups in the number of cases with HAV Ab seropositivity. Significant intergroup differences were noted in this respect: 21-25 years, 2/152 (1.3%); 26-30 years, 33/245 (13.5%); 31-35 years, 70/148 (47.3%); 36-40 years, 52/79 (65.8%); >40 years, 44/48 (91.7%). CONCLUSION: The number of seropositive cases was low among young healthy personnel: low seropositivity is an emerging risk for vulnerable population. With the increase in the incidence of hepatitis A, healthcare personnel have become a risk population for hepatitis A, as are community residents. Therefore, for healthcare personnel working in hospitals, immunization against HAV should be recommended for personnel younger than 30 years, and serological testing for older personnel.

In vitro Expansion of Natural Regulatory T Lymphocytes Useful for Cell Therapy in Allotransplantation

Immunotherapy with regulatory T lymphocytes is considered to be an attractive new therapeutic modality to prevent allograft rejection. The success of this new therapy is critically dependent on the preparation of highly effective and enough number of regulatory T cells. Here, we tried to establish a proper strategy for the ex vivo expansion of regulatory T cells and evaluated their characteristics. CD4+CD25h+CD62L+ T cells were isolated from the recipient mice and weekly stimulated with various stimuli in the presence of IL-2. The most efficient protocol for the expansion of regulatory T cells maintaining Foxp3 expression and regulatory activity was the three cycles stimulation with donor bone marrow-derived dendritic cells (BM-DCs) which yielded around 400 fold expansion of regulatory T cells. The in vitro-expanded regulatory T cells expressing lymph node homing receptors on their cell surface, were composed of polyclonal population, and did not acquire the ability to produce effector cytokines. Importantly, these expanded regulatory T cells induced a modest prolongation of skin allograft survival when combined with transient T cell depletion in recipient mice. These data indicate that our protocol could be used to obtain an effective population of natural regulatory T cells available for the regulatory T cell therapy to prevent allograft rejection.

Experimental Micro Encapsulation of Pancreatic Islets with Air-driven Droplet Generator and Alginate / 대한이식학회지

PURPOSE: Transplantation of microencapsulated islets is proposed as an ideal therapy for the treatment of type 1 diabetes mellitus without immunosuppression. This is based on the principle that foreign cells are protected from the host immune system by an artificial membrane. The aim of this study is to establish an ideal condition of microencapsulation by using an air-driven droplet generator and alginate in vitro. METHODS: Islets were prepared from Sprague Dawley rat and semi SPF-micro pig. Alginate concentrations were changed from 1.5% to 3.0%, and inflow rate of alginate was varied from 10 mL/hr to 40 mL/hr. CO2 flow rate was regulated from 2.0 L/min to 4.0 L/min. Viability was checked by dithizone and FDA/PI staining. Secretory function was tested with glucose challenge and insulin stimulation index was investigated. RESULTS: The optimal conditions for islet encapsulation were revealed with alginate inflow rate of 10 mL/hr, CO2 flow rate of 2.0 L/min in concentration of 2% alginate. In concentration of 2.5% alginate, alginate inflow rate of 20 mL/hr, CO2 flow rate 3.0 L/min was ideal, and alginate inflow rate of 40 mL/hr, CO2 flow rate of 4.0 L/min showed good conditions of microcapsules in concentration of 3% alginate. Viability of encapsulated islets was higher than 90% in both rat and porcine. In terms of insulin secretion, encapsulated islets secreted insulin in response to glucose in static culture medium. However there was no normal response to low and high glucose challenge with stimulation index of less than 2.0. CONCLUSION: Microencapsulation of islets in rat and pig was successful with air-driven droplet generator and alginate in vitro. Further studies about biocompatibility and glucose control in vivo should be followed to be a useful tool for treatment of diabetes mellitus patients in clinical setting.

The Usage of Uncrossmatched Group O, Rh-Negative RBCs for Emergency Transfusion / 대한수혈학회지

BACKGROUND: The use of uncrossmatched group O, Rh-negative RBCs has enabled immediate transfusion of patients who need critical care in life-threatening situations. We examined our 1-year experience with uncrossmatched group O, Rh-negative RBC transfusion in a tertiary care university hospital. METHODS: Uncrossmatched group O, Rh-negative RBCs were available for immediate transfusion upon request without performing any of the following pretransfusion tests: ABO and RhD typing, irregular antibody screening, crossmatching test. The characteristics of the transfused patients were studied retrospectively. RESULTS: Twenty-five patients received 56 units of uncrossmatched group O, Rh-negative RBCs from November 2005 to October 2006. An average of 2.24 units was issued to each patient, with no more than 4 units per patient being given; subsequent transfusion was done with type-specific, crossmatched blood. The average turnaround time for the release of uncrossmatched group O, Rh-negative RBCs was 1.8 minutes (mean+/-standard deviation: 1.8+/-1.96, range: 0~7 minutes). Seventeen patients died (68%), which included 16 patients who had received cardiopulmonary resuscitation. CONCLUSION: Patients admitted for traffic accident, falling down injury, gastrointestinal bleeding and aortic dissection received 72% of the emergency group O, Rh-negative RBCs, with a 72.2% mortality rate, which indicates the dire condition of these patients. The majority of RBCs for transfusion were available within 5 minutes upon request. Though group O, Rh-negative RBCs are recommended in emergency situations in which the blood group of the patient is unknown, the use of group O, Rh-positive RBCs may be an alternative blood supply, when considering the short supply of Rh-negative RBCs.

Comparison Between a New Low Dose Urea Capsule Test and the Conventional UBiT(R) Tablet Test for the Detection of Helicobacter pylori Infection / 대한진단검사의학회지

BACKGROUND: The urea breath test (UBT) is regarded as a highly reliable, noninvasive tool for diagnosing Helicobacter pylori infection. We compared a recently developed low-dose 38 mg 13C-urea capsule, which is able to eliminate oral urease effects and does not require positional changes during the test, with the conventionally used 100 mg 13C-urea tablet method. METHODS: Thirty-nine volunteers were tested under informed consent with both 13C-UBT methods, Helifinder(R) and UBiT-IR300(R), with a minimum 2-week washout period. The pre-ingestion and 20-minute post-ingestion breath samples were analyzed with an isotope ratio mass spectrometer for Helifinder, and a nondispersive isotope-selective infrared spectrophotometer for UBiT samples. RESULTS: Helifinder method showed excellent agreement with UBiT among 19 positive and 20 negative cases (weighted kappa value, 1.0). Helifinder results (y) showed good agreement but with a proportional bias compared to UBiT results (x) by Passing and Bablok method (y=0.551 X -0.255, r=0.74, P<0.0001). CONCLUSIONS: Since the low-dose 38 mg 13C-urea capsule (Helifinder) test, which is more convenient and economic, showed comparable results with the conventional UBiT method, it can be used as an alternative for the diagnosis of H. pylori infection.

Endogenous Endophthalmitis by Aspergillus in a Patient with Multiple Myeloma / 대한진단검사의학회지

A 40-year-old man who had been treated for multiple myeloma, complained of decreased visual acuity of the left eye on the 30th day of admission. The nucleotide sequences of a fungal PCR product from vitreous fluid showed 99% homology with Aspergillus fumigatus (AY373851). Aspergillus spp. was isolated from vitreous fluid culture, also. Rapid diagnosis and intervention are critical elements for the Aspergillus endophthalmitis; therefore, it would be helpful to combine the fungal PCR with conventional fungus culture for clinically indicated specimens.

Isolation of Haemophilus aphrophilus and Coagulase-Negative Staphylococci from the Blood of a Patient with Prosthetic Valve Endocarditis / 대한임상미생물학회지

Haemophilus aphrophilus is a facultative anaerobic, gram-negative coccobacillus or bacillus and its growth is stimulated by 5 to 10% CO2. Most Haemophilus species require either exogenous X or V factor or both to grow, but H. aphrophilus can grow without these factors. H. aphrophilus rarely causes invasive infections such as endocarditis, septicemia, pneumonia and peritonitis in human. Two cases of infective endocarditis by H. aphrophilus have been reported in Korea. However, there has been no report of polymicrobial endocarditis by H. aphrophilus and other bacteria. We isolated H. aphrophilus and coagulase-negative staphylococci (CNS) from the blood of a 38-year-old woman with prosthetic valve endocarditis. She underwent an emergent operation and a culture of the prosthetic valve grew H. aphrophilus. Brain abscess was developed at hospital day 11. H. aphrophilus was susceptible to all antibiotics tested such as ampicillin and cefotaxime, and CNS was susceptible to oxacillin and vancomycin. The patient responded well to therapy with ceftriaxone, teicoplanin, and gentamicin.

Catechins inhibit angiotensin II-induced vascular smooth muscle cell proliferation via mitogen-activated protein kinase pathway

Catechins, components of green tea, reduce the incidence of cardiovascular diseases such as atherosclerosis. Angiotensin II (Ang II) is highly implicated in the proliferation of vascular smooth muscle cells (VSMC), resulting in atherosclerosis. The acting mechanisms of the catechins remain to be defined in the proliferation of VSMC induced by Ang II. Here we report that catechin, epicatechin (EC), epicatechingallate (ECG) or epigallocatechingallate (EGCG) significantly inhibits the Ang II-induced [3H]thymidine incorporation into the primary cultured rat aortic VSMC. Ang II increases the phosphorylation of the extracellular signal-regulated protein kinase 1/2 (ERK 1/2), c-jun-N-terminal kinase 1/2 (JNK 1/2), or p38 mitogen-activated protein kinases (MAPKs) and mRNA expression of c-jun and c-fos. The EGCG pretreatment inhibits the Ang II-induced phosphorylation of ERK 1/2, JNK 1/2, or p38 MAPK, and the expression of c-jun or c-fos mRNA. U0126, a MEK inhibitor, SP600125, a JNK inhibitor, or SB203580, a p38 inhibitor, attenuates the Ang II-induced [3H]thymidine incorporation into the VSMC. In conclusion, catechins inhibit the Ang II-stimulated VSMC proliferation via the inhibition of the Ang II-stimulated activation of MAPK and activator protein-1 signaling pathways. The antiproliferative effect of catechins may be associated with the reduced risk of cardiovascular diseases by the intake of green tea. Catechins may be useful in the development of prevention and therapeutics of vascular diseases.

Resveratrol derivatives potently induce apoptosis in human promyelocytic leukemia cells

Resveratrol has been shown to possess antioxidant and anticancer activities, but little is known on the effect of resveratrol derivatives. Recently we have isolated resveratrol and its dimers and trimers from peony (Paeonia lactiflora) seeds, and reported their strong antioxidant and cytotoxic activity. In the present study, we have evaluated cellular effects of resveratrol derivatives; viniferin, gnetin H, and suffruticosol B on the proliferation and apoptosis in HL-60 cells in vitro. All resveratrol and its derivatives reduced viability of HL-60 cells in a dose-dependent manner with their IC(50)values of 20-90 micrometer. Ascending orders of IC(50)values were suffruticosol B, gnetin H, viniferin and resveratrol respectively. HL-60 cells treated with the four stilbenes exhibited the distinct morphological changes characteristics of cell apoptosis such as chromatin condensation, apoptotic bodies, and DNA fragmentations. A time-dependent histogram of the cellular DNA analyzed by flow cytometry revealed a rapid increase in subdiploid cells and a concomitant decrease in diploid cells exposed to 100 micrometer resveratrol for 0-24 h. Cells treated with 25 micrometer of resveratrol, viniferin, gnetin H, and suffruticosol B for 24 h resulted in increment of sub-G1 population by 51, 5, 11 and 59%, respectively. Treatment of cells with 0-20 micrometer resveratrol for 5 h produced a concentration-dependent decrease in cytochrome P450 (CYP) 1B1 mRNA levels. Suffruticosol B also suppressed CYP1B1 gene expression. These results demonstrated that resveratrol oligomers also strongly suppressed HL-60 cell proliferation, and induced DNA damage. In addition, CYP1B1 gene supression may suggest an involvement in the resveratrol-induced apoptosis in HL-60 cells.

A Case of 'ALUM' Intoxication Leading to ARDS / 결핵

A 77-year-old female was admitted 3 hours after intentionally ingesting 5 g of aluminum ammonium sulfate ('Alum') powder dissolved in water. Gastric lavage with normal saline, activated charcoal chelation, and supportive therapies were performed. She showed a high anion gap metabolic acidosis, which rapidly progressed to multiple organ failure including ARDS. The patient subsequently progressed to a refractory shock which eventually led to death.

A Case of 'ALUM' Intoxication Leading to ARDS / 결핵

A 77-year-old female was admitted 3 hours after intentionally ingesting 5 g of aluminum ammonium sulfate ('Alum') powder dissolved in water. Gastric lavage with normal saline, activated charcoal chelation, and supportive therapies were performed. She showed a high anion gap metabolic acidosis, which rapidly progressed to multiple organ failure including ARDS. The patient subsequently progressed to a refractory shock which eventually led to death.

Phytoestrogen-Induced Phosphorylation of MAP Kinase in Osteoblasts is Mediated by Membrane Estrogen Receptor

We have previously demonstrated that phytoestrogens isolated from safflower seeds significantly attenuated bone loss in ovariectomized rats, and directly stimulated proliferation and differentiation of cultured osteoblastic cells. In an attempt to elucidate underlying cellular mechanisms, in the present study we investigated effects of 17beta-estradiol (E2) and phytoestrogens such as matairesinol and acacetin, a type of lignan and flavonoid, respectively, on activation of mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase 1 (ERK1) and ERK2, in cultured osteoblastic ROS 17/2.8 cells. Western blot analysis with anti-MAP kinase antibody showed that a wide range concentrations (10(-14) to 10(-6) M) of E2 as well as both phytoestrogens induced rapid and transient activation of ERK1/2 through phosphorylation within minutes. Maximum activation of MAP kinases by E2 and phytoestrogens were observed at 10 and 15 min, respectively. E2-induced phosphorylation of ERK1/2 returned to the control level at 30 min, whereas phytoestrogen-induced phosphorylation was maintained at high level until 30 min. PD-98059, a highly selective inhibitor of MAP kinase, prevented phosphorylation of ERK1/2 in the cells treated either with E2 or phytoestrogens. To examine a possible involvement of estrogen receptor in the activation process of MAP kinase, Western blot analysis was performed in the presence and absence of the estrogen receptor antagonists, ICI 182,780 and tamoxifen. These antagonists blocked MAP kinase phosphorylation induced not only by E2, but also by the phytoestrogens. To the best our knowledge, this study is the first to demonstrate that phytoestrogens such as flavonoid and lignan extracted from safflower seeds produce a rapid activation of MAP kinase, at least partially via membrane estrogen receptor of the cultured osteoblastic cells.

Amnioinfusion in preterm premature rupture of membranes / 대한산부인과학회잡지

OBJECTIVE: Our purpose was to determine the effectiveness of transabdominal amnioinfusion in the pregnant women with preterm premature rupture of the membranes (PPROM). METHODS: Between March 1997 and June 1999, 54 pregnancies of 26 weeks to 36 weeks of gestation complicated with preterm premature rupture of the membranes were admitted at our institution, 23 patients were excluded from study due to incomplete data, loss follow up or medical diseases was combined. Among included 31 cases were randomly selected either for amnioinfusion (n=16) or expectant management (n=15). After hospitalization, all patients were assessed for fetal heart rate abnormalities, fetal lung maturity and chorioamnionitis. Labor induction was not performed until progressive labor and chorioamnionitis occurred. Amnioinfusion was done through transabdominal catheter and infused group was managed with prophylactic antibiotics and conservative group were treated by hydration and antibiotics. RESULTS: The median interval from PPROM and delivery was significantly increased in amnioinfused group compared to expectant group (11.19+/-11.52 days vs 3.67+/-5.59 days, p=0.02). There were no differences in 1 minute and 5 minutes Apgar score. However, the duration of incubator treatment and oxygen supplementation were more necessary in expectant group compared to amnioinfused group (p=0.01, respectively). Respiratory distress syndrome was more frequent in expectant group although it did not show statistical significance (20% vs 6%, p<0.25). There was no differences in mode of delivery, birth weight and maternal clinical characteristics between two groups. CONCLUSION: Our results suggest that active management using transabdominal amnioinfusion in pregnancies complicated with PPROM may give a chance to gain minimal time to accelerate lung maturation and thus improve neonatal outcome without increasing complications.

A Case of Malignant Lymphoma originated from uterine cervix / 대한산부인과학회잡지

The malignant lymphomas are neoplastic transformation of cells that reside predominantly in lymphoid tissues. The two major variants of malignant lymphoma are non-Hodgkin's lymphoma and Hodgkin's disease. Although both of these tumors infiltrate reticuloendothelial organs, their biologic and clinical behaviors suggest that they are probably not related. More than 90% of all cases of non-Hodgkin's lymphomas are of B-cell derivation. This observation is based upon the expression of B-lineage-restricted antigens as well as clonal rearrangements of immunoglobulin heavy and light chain genes. The malignant lymphoma localized in uterine cervix is rare and characteristically symptom-free expressed. We experienced a case of malignant lymphoma originated from uterine cervix, so we report with a brief of literature.

A Case of Acardiac Parabiotic Twin / 대한산부인과학회잡지

Acardia is a very rare congenital anomaly occurring in less than 1 in 35,000 deliveries. Acardiac parabiotic twin has been reported only in multiple, monochronic pregnancies. This anomalous fetus is sustained in utero by parasitic anastomoses to the circulation of its usually normal co-twin and is therefore not compatible with extrauterine survival. A case of an acardiac parabiotic twin is described, and the literature concerning the incidence, classification and etiology of acardiac is reviewed.

A Case of Rhabdomyolsis and Acute Renal Failure Associated with Tsutsugarnushi Disease / 대한신장학회잡지

We first report a case that demonstrates superi-mposed acute renal failure associated with rhabdo-myolysis in a patient with tsutsugamushi disease. The clinical presentation was that of insidious onset of fever, abdominal pain, back pain, renal failure and respiratory failure over about 20 days period. The renal function was progressively deteriorated and the serum creatinine concentration increased from 1.4 to 8.4mg/dL, while the patient was in a state of septic shock caused by tsutsugamushi disease. The laboratory data including increased muscle enzymes such as CK, LDH, SGOT, myoglobin, positive test for urine myoglobin, and increased uptake of bone scan were consistent with rhabdomyolysis. On consideration of the cause of rhabdomyolysis in this patient, endotoxin made in the state of septic shock had triggered a muscle necrosis and acute renal failure aggravated by dehydration and metabolic acidosis. She was recovered by the proper use of a IV doxycycline as the therapy of tsutsugamushi disease with a maintenance of renal blood flow by hydration, mannitol, bicarbonate and protection of hypotension. We suggest that rickettsial disease, especially tsutsugamushi disease can result in the acute renal failure by rhabdomyolysis.