• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.1
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• pp.19-25
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• 2006

With particular regards to the hepatitis A virus (HAV), a terminal dry-heat treatment ($100^{\circ}C$ for 30 min) process, following lyophilization, was developed to improve the virus safety of a solvent/detergent-treated antihemophilic factor IX concentrate. The loss of factor IX activity during dry-heat treatment was of about 3%, as estimated by a clotting assay. No substantial changes were observed in the physical and biochemical characteristics of the dry-heat-treated factor IX compared with those of the factor IX before dry-heat treatment. The dry-heat-treated factor IX was stable for up to 24 months at $4^{\circ}C$, The dry-heat treatment after lyophilization was an effective process for inactivating viruses. The HAV and murine encephalomyocarditis virus (EMCV) were completely inactivated to below detectable levels within 10 min of the dry-heat treatment. Porcine parvovirus (PPV) and bovine herpes virus (BHV) were potentially sensitive to the treatment. The log reduction factors achieved during lyophilization and dry-heat treatment were ${\ge}5.60$ for HAV, ${\ge}6.08$ for EMCV, 2.64 for PPV, and 3.59 for BHV. These results indicate that dry-heat treatment improves the virus safety of factor IX concentrates, without destroying the activity. Moreover, the treatment represents an effective measure for the inactivation of non-lipid enveloped viruses, in particular HAV, which is resistant to solvent/detergent treatment.

• KSBB Journal
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• v.23 no.1
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• pp.37-43
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• 2008

The use of antihemophilic factor IX complex has been associated with a variety of thrombotic complications, the major cause of which was the contamination of thrombogenic proteins such as vitamin K-dependent clotting factors II, VII, and X. In order to produce a commercial factor IX (GreenNine VF) free from thrombogenic potential, industrial-scale production process for high-purity factor IX from human plasma has been developed. The purification process contains cryo-precipitation, DEAE-sephadex A-50 anion-exchange chromatography, DEAE-toyopearl 650M anion-exchange column chromatography, heparin-sepharose 6FF affinity column chromatography, and CM-sepharose FF cation-exchange column chromatography. Also the process includes two viral inactivation and removal procedures, solvent/detergent treatment and nanofiltration using Viresolve NFP filter. The purification yield was 35.4%. The specific activity in the purified concentrate was 190.8 IU/mg which exceeded that in the factor IX complex (FacNine) by a factor of 48. The activities of factor II, VII, and X were not detected in GreenNine VF. SDS-PAGE analysis showed that GreenNine VF had the highest purity in comparison with commercially available high purity factor IX concentrates, Mononine, Octanyne, Berinin HS, and Immunine STIM plus 600. One batch size of the production was 2,400 vials of 250 IU product or 1,200 vials of 500 IU product from 1,600 L cryo-poor plasma.

• Journal of Microbiology and Biotechnology
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• v.18 no.7
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• pp.1317-1325
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• 2008

Viral safety is an important prerequisite for clinical preparations of plasma-derived pharmaceuticals. One potential way to increase the safety of therapeutic biological products is the use of a virus-retentive filter. In order to increase the viral safety of human antihemophilic factor IX, particularly in regard to non-enveloped viruses, a virus removal process using a polyvinylidene fluoride membrane filter (Viresolve NFP) has been optimized. The most critical factor affecting the filtration efficiency was operating pH and the optimum pH was 6 or 7. Flow rate increased with increasing operating pressure and temperature. Recovery yield in the optimized production-scale process was 96%. No substantial changes were observed in the physical and biochemical characteristics of the filtered factor IX in comparison with those before filtration. A 47-mm disk membrane filter was used to simulate the process performance of the production-scale cartridges and to test if it could remove several experimental model viruses for human pathogenic viruses, including human hepatitis A virus (HAV), porcine parvovirus (PPV), murine encephalomyocarditis virus (EMCV), human immunodeficiency virus type 1 (HIV), bovine viral diarrhea virus (BVDV), and bovine herpes virus (BHV). Non-enveloped viruses (HAV, PPV, and EMCV) as well as enveloped viruses (HIV, BVDV, and BHV) were completely removed during filtration. The log reduction factors achieved were $\geq$6.12 for HAV, $\geq$4.28 for PPV, $\geq$5.33 for EMCV, $\geq$5.51 for HIV, $\geq$5.17 for BVDV, and $\geq$5.75 for BHV. These results indicate that the virus filtration process successfully improved the viral safety of factor IX.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.237-242
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• 2015

The coagulation factor activity compared two groups of the lower 10% (29.1~30.9 sec) and the upper 10% (38.0~41.9 sec) of the normal reference range of aPTT. The aim of this study was to investigate the influence of sex, age, and ABO blood type on coagulation factor activity. There was significant difference in the activity of the coagulation factor assay based on age. The VIII (p<0.0001) and IX (p=0.0050) in the lower group of samples from those over sixty years of age is higher than from those under sixty. In contrast, XII (p=0.0285) for samples over sixty was lower than for samples under sixty. While in the upper group V (p=0.0219), VIII (p=0.0005), and IX (p=0.0014) for samples from the over sixty group was higher than those under sixty. In the case of activity of coagulation factor between O and non-O blood type, VIII (p<0.001) activity of the non-O blood type was higher than that of the O blood type in the both groups. The XII (p=0.016) activity of non-O blood type was lower than that of O blood type in the upper group. According to the multiple logistic regression analysis, when other variables are under the same conditions between lower and upper groups, there is a strong possibility for the lower group when activity of V (p=0.001), VIII (p<0.001), X (p<0.001) and XII (p<0.001) is increased. Furthermore, there is also a strong possibility of upper group when activity of II (p=0.004) and IX (p=0.012) is increased. However, no significant difference in between sex, age and XI was observed.

• Journal of Genetic Medicine
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• v.13 no.2
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• pp.89-94
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• 2016

Purpose: Molecular genetic analysis is the main approach used for prenatal diagnosis of hemophilia A and B. However, in certain cases, such analysis is uninformative. In such situations, direct measurement of fetal coagulation factor levels is still the best option, and it may be the only option in some cases. This study was conducted to determine the normal ranges of mid-trimester cord blood factor VIII (FVIII) and IX (FIX) in a Korean population. Materials and Methods: Twenty-six FVIII samples and 29 FIX samples were assayed in fetal cord blood acquired by ultrasound-guided cordocentesis. Sampling was conducted during gestational ages of 19-24 weeks. Results: The mean and standard deviations for FVIII and FIX activity were $45.5{\pm}30.5%$ and $19.9{\pm}12.2%$, respectively. Ranges for FVIII and FIX were 1.5-125.0% and 6.0-52.0%, respectively. Conclusion: Our study revealed the normal ranges and lowest level of factor VIII and factor IX in non-affected normal fetus by fetal cord blood sampling during the mid-trimester in a Korea population. The factor assay of the fetal cord blood is invasive but feasible and provides important basic data related to hemophilia.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8923-8929
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• 2014

Background: Increasing evidence suggests that stromal monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX) may play key roles in tumor development. However, their clinical value remains largely unexplored in gastric cancer (GC). The present study aimed to determine clinicopathological significance and prognostic values of stromal MCT4 and CA IX in GC. Materials and Methods: Specimens from 143 GC patients were immunohistochemically stained using polyclonal anti-MCT4 and anti-CA IX antibodies. Expression was correlated with patient clinicopathologic characteristics and survival data. Results: High stromal MCT4 expression was detected in 72 of 143 (50.3%) GCs and high CA IX in 74 (51.7%). Both high stromal MCT4 and CA IX were correlated with advanced TNM stage (p=0.000; p=0.000). High CA IX expression was positively related to depth of invasion (p=0.022) and positive lymph nodes (p=0.002) as well. Survival analysis indicated high expression of stromal MCT4 to be an independent factor in predicting poor overall survival (OS) (HR and 95%CI=1.962, 1.032-3.729, p=0.040) and disease free survival (DFS) (HR and 95%CI=2.081, 1.158-3.741, p=0.014) of GC patients. However, high CA IX expression exhibited no significant predictive value. Conclusions: These findings suggest that high expression of stromal MCT4 and CA IX proteins is significantly correlated with GC progression. High stromal MCT4 heralds worse outcome of GC patient, suggesting a novel candidate prognostic marker and therapeutic target.

• Archives of Plastic Surgery
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• v.39 no.2
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• pp.150-153
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• 2012

Hemophilia B is a rare blood coagulation disorder. Complications such as bleeding and hematoma can cause necrosis of flaps, wound disruption, and the disturbance of wound healing. In particular, guidelines for flap operations in hemophilia B patients have still not been defined, and case reports are rare. We reconstructed the heel of a 41-year-old male hemophilia B patient using a reverse sural artery flap operation. The patient presented with mild hemophilia, having 27% of the normal value of coagulation factor IX. Coagulation and the changing value of the coagulation factor were regularly measured, and 70% of the normal value of coagulation factor IX was maintained through the injection of recombinant coagulation factors and antihemorrhagics. Hematoma developed twice (postoperative day [POD] 5 and POD 7) and in each case the hematoma was removed. Injections of recombinant coagulation factors and antihemorrhagics were continuously administered until postoperative week 2. When the coagulation factors were within normal ranges. In this article, a hemophilia B patient underwent reverse sural artery flap surgery and the healing progress was analyzed. We conclude that higher than baseline levels of coagulation factors are needed for successful healing in reverse sural artery flap surgery.

• Nuclear Engineering and Technology
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• v.55 no.2
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• pp.640-647
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• 2023

Material corrosion in nuclear power plant (NPP) is not controlled only by amine injection but also by ion exchange (IX) which is the best option to remove trace Na⁺. This study was conducted to understand the Na⁺ leakage characteristics of IX beds packed with ethanolamine-form (ETAH-form) and hydrogen-form (H-form) resins in the simulated water-steam cycle in terms of intrinsic behaviors of four kinds of cation-exchange resins through ASTM test and Vanselow mass action modeling. Na⁺ was inappreciably escaped throughout the channel created in resin layer. Na⁺ leakage from IX bed was non-linearly raised because of its decreasing selectivity with increasing Na⁺ capture and with increasing the fraction of ETAH-form resin. Na⁺ did not reach the breakthrough earlier than ETAH⁺ and NH₄⁺ due to the increased selectivity of Na⁺ to the cation-exchange resin (H⁺ < ETAH⁺ < NH₄⁺ ≪ Na⁺) at the feed composition. Na⁺ leakage from the resin bed filled with small particles was decreased due to the enhanced dynamic IX processes, regardless of its low selectivity. Thus, the particle size is a predominant factor among intrinsic properties of IX resin to reduce Na⁺ leakage from the condensate polishing plant (CPP) in NPPs.

• Korean Journal of Veterinary Service
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• v.34 no.2
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• pp.191-193
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• 2011

A 3-month-old intact male, Labrador retriever was presented with the history of coagulopathy and anemia. The results of initial screening tests of the hemostatic system yielded a tentative diagnosis of hemophilia. Activated partial thromboplastin time (APTT) was distinctly prolonged (106 seconds) and prothrombin time (PT) was not detected due to markedly prolonged test time. Whole blood transfusions (20 me l/kg body weight) were carried out prior to assays of coagulation factor. After transfusion, the patient recovered well and hemorrhage ceased. Blood samples were assessed for coagulation factor activity. The patient showed markedly low factor IX coagulation activity (5%, reference range: 7~140%) and was diagnosed with hemophilia B. After recovery, the patient was discharged from the hospital. However, 4 months later the patient was re-hospitalized for recurrence of the initial symptoms. The owner did not want to pursue further treatment and the patient died of respiratory distress two days later.

• The Transactions of the Korean Institute of Power Electronics
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• v.4 no.6
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• pp.539-546
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• 1999

A new integrated single-stage zero current switched(ZCS) quasi resonant convertedQRC) for the IX)wer f factor correction(PFCl converter is introduced in this paper. The power factor correction can be achieved by t the discontinuous conduction mod$\varepsilon$(DCM) operation of an input current. The proposed converter has the c characteristics of the good IX)wer factor, 10씨 line current harmonics, and tight output regulation. Furthern10re, t the ringing effect due to the output capacitance of the main switch can be eliminated by use of‘ active clamp c circuit. Therefore, the proIX)sed converter is expecttc'(] to be suitable for a compact power converter with a t tightly regulated output voltage requiring a switching frequency of more than several hundrtc'(]s kHz.