Background: Flow cytometric immunophenotyping of hematolymphoid neoplasms (FCIHLN) is essential for diagnosis, classification, and minimal residual disease (MRD) monitoring. FCI-HLN is typically performed using in-house protocols, raising the need for standardization. Therefore, we surveyed the current status of FCI-HLN in Korea to obtain fundamental data for quality improvement and standardization. Methods: Eight university hospitals actively conducting FCI-HLN participated in our survey.We analyzed responses to a questionnaire that included inquiries regarding test items, reagent antibodies (RAs), fluorophores, sample amounts (SAs), reagent antibody amounts (RAAs), acquisition cell number (ACN), isotype control (IC) usage, positiveegative criteria, and reporting. Results: Most hospitals used acute HLN, chronic HLN, plasma cell neoplasm (PCN), and MRD panels. The numbers of RAs were heterogeneous, with a maximum of 32, 26, 12, 14, and 10 antibodies used for acute HLN, chronic HLN, PCN, ALL-MRD, and multiple myeloma-MRD, respectively. The number of fluorophores ranged from 4 to 10. RAs, SAs, RAAs, and ACN were diverse. Most hospitals used a positive criterion of 20%, whereas one used 10% for acute and chronic HLN panels. Five hospitals used ICs for the negative criterion. Positiveegative assignments, percentages, and general opinions were commonly reported. In MRD reporting, the limit of detection and lower limit of quantification were included. Conclusions This is the first comprehensive study on the current status of FCI-HLN in Korea, confirming the high heterogeneity and complexity of FCI-HLN practices. Standardization of FCI-HLN is urgently needed. The findings provide a reference for establishing standard FCI-HLN guidelines.

Background/Aims: Membranous nephropathy (MN) is a major cause of nephrotic syndrome in adults. This study aimed to evaluate the effect of rituximab (RTX) in patients with idiopathic MN (iMN) who have a high risk of progression. Methods: We retrospectively analyzed data of 13 patients with iMN, who received RTX treatments from January 2014 to July 2020. RTX was indicated in patients with iMN with severe proteinuria and decreasing estimated glomerular filtration rate (eGFR) in the previous 6 months despite other immunosuppressive therapies. Results: The patients were predominantly males (n = 11) and with a mean age of 55.3 years; median eGFR, 37.0 mL/min/1.73 m2 (interquartile range [IQR], 26.3 to 66.5); serum albumin level, 2.6 g/dL (IQR, 1.9 to 3.1); and spot urine protein-to-creatinine ratio at baseline, 6.6 g/g (IQR, 5.7 to 12.9). In a median follow-up of 22 months, eight patients (61.5%) achieved complete or partial remission. In responder group (n = 8), median eGFR increased from 31.5 to 61.5 mL/min/1.73 m2 (p = 0.049) and serum albumin level increased from 2.3 to 4.2 g/dL (p = 0.017) from RTX initiation to last follow-up. Antiphospholipase A2 receptor antibody (anti-PLA2R-Ab) was positive in six among seven tested patients, which markedly decreased in the responder group. There were no adverse events after RTX. Conclusions This study suggests that RTX is a safe and effective treatment option for patients with iMN who have a high risk of progression. Individualized therapy based on anti-PLA2R-Ab titer would be needed for better outcomes.

PURPOSE: Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. We tested whether quantification of urinary TG2 may represent a noninvasive method to estimate the severity of kidney allograft fibrosis. METHODS: We prospectively collected urine specimens from 18 deceased donor kidney transplant recipients at 1-day, 7-day, 1-month, 3-month, and 6-month posttransplant. In addition, kidney allograft tissue specimens at 0-day and 6-month posttransplant were sampled to analyze the correlation of urinary TG2 and kidney allograft fibrosis. RESULTS: Thirteen recipients had increased interstitial fibrosis and tubular atrophy (IFTA) scores at the 6-month protocol biopsy (IFTA group). The mean level of urinary TG2 in the IFTA group was higher compared to that of 5 other recipients without IFTA (no IFTA group). Conversely, the mean level of urinary syndecan-4 in the IFTA group was lower than levels in patients without IFTA. In the IFTA group, double immunofluorescent staining revealed that TG2 intensity was significantly upregulated and colocalizations of TG2/heparin sulfate proteoglycan and nuclear syndecan-4 were prominent, usually around tubular structures. CONCLUSION: Urinary TG2 in early posttransplant periods is a potent biomarker for kidney allograft inflammation or fibrosis.
Allografts ; Atrophy ; Biomarkers ; Biopsy ; Extracellular Matrix ; Fibrosis ; Humans ; Inflammation ; Kidney Transplantation ; Kidney ; Methods ; Prospective Studies ; Proteoglycans ; Syndecan-4 ; Tissue Donors ; Transplant Recipients

BACKGROUND: This study evaluated the efficacy of ulinastatin for attenuating organ injury and the release of proinflammatory cytokines due to cardiopulmonary bypass (CPB) during cardiac surgery. METHODS: Patients undergoing valvular heart surgery employing CPB were assigned to receive either ulinastatin (group U, n = 13) or a placebo (group C, n = 11) before the commencement of CPB. Hemodynamic data, parameters of major organ injury and function, and proinflammatory cytokines were measured after the induction of anesthesia (T1), after CPB (T2), at the end of anesthesia (T3), and at 24 hours after surgery (POD). RESULTS: The demographic data, CPB duration, and perioperative transfusions were not different between the groups. PaO2/FiO2 in group U was significantly higher than that in group C at T3 (3.8 +/- 0.8 vs. 2.8 +/- 0.7, P = 0.005) and at POD (4.0 +/- 0.7 vs. 2.8 +/- 0.7, P < 0.001). Creatine kinase-MB at POD in group U was significantly lower than that in group C (17.7 +/- 8.3 vs. 33.7 +/- 22.1, P = 0.03), whereas troponin I at POD was not different between the groups. Creatinine clearance and the extubation time were not different between the groups at POD. The dopamine infusion rate during the post-CPB period in group U was significantly lower than that in group C (1.6 +/- 1.6 vs. 5.5 +/- 3.3 microg/kg/min, P = 0.003). The interleukin-6 and tumor necrosis factor-alpha concentrations at T1, T2, and T3 as well as the incidences of postoperative cardiac, pulmonary and kidney injuries were not different between the groups. CONCLUSIONS: Ulinastatin pretreatment resulted in an improved oxygenation profile and reduced inotropic support, probably by attenuating the degree of cardiopulmonary injury; however, it did not reduce the levels of proinflammatory cytokines.
Anesthesia ; Cardiopulmonary Bypass ; Creatine ; Creatinine ; Cytokines ; Dopamine ; Glycoproteins ; Hemodynamics ; Humans ; Incidence ; Interleukin-6 ; Kidney ; Oxygen ; Thoracic Surgery ; Troponin I ; Tumor Necrosis Factor-alpha

OBJECTIVE: Preimplantation genetic diagnosis (PGD) is an assisted reproductive technique for couples carrying genetic risks. Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy, with a prevalence rate of 1/2,500. In this study, we report on our experience with PGD cycles performed for CMT types 1A and 2F. METHODS: Before clinical PGD, we assessed the amplification rate and allele drop-out (ADO) rate of multiplex fluorescent polymerase chain reaction (PCR) followed by fragment analysis or sequencing using single lymphocytes. We performed six cycles of PGD for CMT1A and one cycle for CMT2F. RESULTS: Two duplex and two triplex protocols were developed according to the available markers for each CMT1A couple. Depending on the PCR protocols, the amplification rates and ADO rates ranged from 90.0% to 98.3% and 0.0% to 11.1%, respectively. For CMT2F, the amplification rates and ADO rates were 93.3% and 4.8%, respectively. In case of CMT1A, 60 out of 63 embryos (95.2%) were diagnosed and 13 out of 21 unaffected embryos were transferred in five cycles. Two pregnancies were achieved and three babies were delivered without any complications. In the case of CMT2F, a total of eight embryos were analyzed and diagnosed. Seven embryos were diagnosed as unaffected and four embryos were transferred, resulting in a twin pregnancy. Two healthy babies were delivered. CONCLUSION: This is the first report of successful pregnancy and delivery after specific PGD for CMT disease in Korea. Our PGD procedure could provide healthy babies to couples with a high risk of transmitting genetic diseases.
Alleles ; Charcot-Marie-Tooth Disease* ; Embryonic Structures ; Family Characteristics ; Korea ; Lymphocytes ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy, Twin ; Preimplantation Diagnosis* ; Prevalence ; Prostaglandins D ; Reproductive Techniques, Assisted

The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-kappaB activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin E2-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-alpha production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.
Acetates ; Animals ; Arthritis* ; Atherosclerosis ; Cartilage ; Cartilage, Articular ; Edema ; Freund's Adjuvant ; Ganglia, Spinal ; Human Umbilical Vein Endothelial Cells ; Indomethacin ; Inflammation ; Jurisprudence ; Methanol ; NF-kappa B ; Rats* ; Tumor Necrosis Factor-alpha ; Up-Regulation ; Vascular Endothelial Growth Factor A

No abstract available.
Anesthesia ; Cardiopulmonary Bypass ; Humans ; Lung ; Pneumothorax

PURPOSE: The cause of aseptic meningitis remains mostly unknown because viral culture and identification is difficult. Thus, we report a study on 123 children with aseptic meningitis in Gyeongju in 2002 to identify the causing virus and the relationship with the clinical manifestation. METHODS: We prospectively investigated the patients, admitted to Dongguk University Hospital, into two groups between April and October 2002. Group 1 included 123 patients diagnosed as aseptic meningitis. Group 2, the adimssion control, included 120 patients, who suffered from none-enteroviral diseases. Specimens of CSF and stool were collected to perform reverse transcription polymerase chain reaction(RT-PCR), and enteroviral culuture was done in RT-PCR positive patients as well. RESULTS: The male to female sex ratio was 2.2:1 and the mean age was 6.2+/-3.7 years. The clinical manifestations were fever, headache and vomiting. The RT-PCR for enterovirus, performed in 58 cases of CSF in group 1, showed 5.2% positive results and negative result in viral culture. The RT-PCR for enterovirus used in stool specimens showed 89.3% and 41.1% of positive results in group 1 and group 2, respectively. Viral culture of stool specimens showed five cases of echovirus 13 and four cases of echovirus 6 in group 1, whereas three cases of echovirus 6 and one case of coxsackie B4 were detected in group 2. CONCLUSION: The etiologic viruses of the aseptic meningitis outbreak in Gyeongju in 2002 is presumed to be echovirus 13 and echovirus 6. Since echovirus 13 firstly appeared with various age distributions, the outbreak may have emerged due to a lack of acquisition of immunity to this virus.
Age Distribution ; Child ; Echovirus 6, Human ; Enterovirus ; Enterovirus B, Human ; Female ; Fever ; Gyeongsangbuk-do ; Headache ; Humans ; Male ; Meningitis, Aseptic* ; Prospective Studies ; Reverse Transcription ; Sex Ratio ; Vomiting

BACKGROUND: Although leptin and its principal mediators, neuropeptide Y (NPY) and -melanocyte stimulating hormone (MSH) are postulated to play a pivotal role in the energy balance in experimental animals, the physiologic roles of leptin and its molecular targets are not fully identified in cases of human obesity. METHODS: The subjects consisted of 16 obese women (mean BMI 35.6 kg/m2) before and after weight loss that was induced by a 2 week-very low caloric diet (800 kcal/day) and 14 normal weight women (who had a mean BMI of 20.4 kg/m2). We evaluated the plasma and cerebrospinal fluid (CSF) leptin, NPY and alpha -MSH levels and their relationship in normal weight and obese women. Additionally, changes of these peptides during a negative energy balance (800 kcal/day) were assessed in causes of human obesity. RESULTS: Obese subjects exhibited a 6.3-fold higher plasma leptin level (21.9+/-1.2 vs 3.5+/-0.4 ng/mL, p<0.05) and a 2.8-fold higher CSF leptin level (0.29+/-0.02 vs 0.10+/-0.01 ng/mL, p<0.05) compared to control subjects. The CSF/plasma leptin ratio in normal weight subjects was 2.3-fold higher than that in obese subjects. After a weight loss in obese subjects, the plasma leptin level decreased by 40% and the CSF level decreased by 51%. The CSF/plasma leptin ratio was slightly lower than the baseline level. There was a positive linear correlation between CSF and plasma leptin level at the baseline in obese subjects (r= 0.74, p<0.05) and a positive logarithmic correlation in normal weight subjects and in obese subjects after a weight loss (r= 0.66, p<0.05). The BMI negatively correlated with the CSF/plasma leptin ratio (r=-0.86, p<0.05) in any subjects. Neither the baseline plasma levels nor the baseline CSF levels of NPY were different between the normal weight subjects and obese subjects. After a weight loss the CSF NPY level decreased significantly compared to the baseline values in obese subjects. The alpha -MSH levels in plasma and CSF did not differ significantly from controls in obese subjects at the baseline or after a weight loss. The baseline CSF leptin level neither correlated with the baseline CSF NPY level nor the baseline CSF alpha -MSH level. CONCLUSION: These results demonstrated that the efficiency of leptin delivery to the CNS is reduced in human obesity and that the CNS leptin uptake involves the combination of saturable and unsaturable mechanisms. A marked reduction in the CSF leptin levels compared to the plasma level after a weight loss in obese subjects can be a potent stimulus for the body to regain weight. In contrast to the results that were observed in experimental animals, the CSF NPY and alpha -MSH did not differ from the controls in human obesity and there was no significant correlation between the CSF leptin and CSF of these neuropeptides. This could have resulted from leptin resistance in cases of human obesity although the mechanisms for this resistance remain to be determined.
alpha-MSH ; Animals ; Cerebrospinal Fluid* ; Diet ; Female ; Humans ; Leptin* ; Neuropeptide Y ; Neuropeptides ; Obesity ; Peptides ; Plasma* ; Weight Loss*

A prospective study was initiated to compare maternal serum concentration of CA-125 during the first trimester of normal and abnormal pregnancies. Serum specimens were obtained from 87 women with a normal intrauterine pregnancy and 47 women with abnormal pregnancies which were ended in spontaneo abortion or pathologically confirmed to be missed abortion. In normal pregnancies, the mean serum CA-125 concentrations were increased significantly from amenorhea 6 weeks (139.838.7 IU/ml), and were higher statistically than the values tested in the same weeks of abnormal pregnancies. In abnormal pregnancies serum CA-125 concentations were relatively lower than those of normal pregnancies. But these differences were not statistically significant except the values tested in amenorhea 6weeks. So serum levels of CA-125 may not be proved useful in monitoring of early pregnancies outcome.
Abortion, Missed ; Female ; Humans ; Pregnancy ; Pregnancy Trimester, First* ; Pregnancy* ; Prospective Studies