• The Korean Journal of Nuclear Medicine
• /
• v.33 no.6
• /
• pp.527-536
• /
• 1999

Purpose: Radiotracers that bind to the central benzodiazepine receptor are useful for the investigation of various neurological and psychiatric diseases. [C-11]Flumazenil, a benzodiazepine antagonist, is the most widely used radioligand for central benzodiazepine receptor imaging by PET. We synthesized 3-(2-[F-18]fluoro)flumazenil, a new fluorine-18 ($t_{1/2}$= 110 min) labeled analogue of benzodiazepine receptor imaging agent, and evaluated in vivo for biodistribution in mice. Materials and Methods: Flumazenil (Ro 15-1788) was synthesized by a modification of the reported method. Precursor of 3-(2-[F-18]fluoro)flumazenil, the tosylated flumazenil derivative was prepared by the tosylation of the ethyl ester by ditosylethane. [F-18] labeling of tosyl substitued flumazenil precursor was performed by adding F-18 ion at $85^{\circ}C$ in the hot ceil for 20 min. The reaction mixture was trapped by C18 cartridge, washed with 10% ethanol, and eluted by 40% ethanol. Bidistribution in mice was determined after intravenous injection. Results: The total chemical yield of tosylated flumazenil derivative was ${\sim}40%$. The efficiency of labeling 3-(2-[F-18]fluoro)flumazenil was 66% with a total synthesis time of 50 min. Brain uptakes of 3-(2-[F-18]fluoro)flumazenil at 10, 30, 60 min after injection, were $2.5{\pm}0.37,\;2.2{\pm}0.26,\;2.1{\pm}0.11$ and blood activities were $3.7{\pm}0.43,\;3.3{\pm}0.07,\;3.3{\pm}0.09%ID/g$, respectively. Conclusion: We synthesized a tosylated flumazenil derivative which was successfully labeled with no-carrier-added F-18 by nucleophilic substitution.

• The Korean Journal of Nuclear Medicine
• /
• v.37 no.6
• /
• pp.402-417
• /
• 2003

Purpose: To evaluate the use of monoclonal antibody (MoAb) as a carrier of the receptor-binding ligand the receptor mediated uptake into liver and subsequent metabolism of $^{111}In-labeled$ galactosylated MoAb-chelator conjugates were investigated and compared with those of $^{111}In$ labeled MoAb. Materials and Methods : T101 MoAb, $IgG_2$ against human lymphocytic leukemic cell, conjugated with cyclic DTPA dianhydride (DTPA) or 2-p-isothiocyanatobenzyl-6-methyl-DTPA (1B4M) was galactosylated with 2-imino-2-methoxyethyl-1-thio-${\beta}$-D-galactose and then radiolabeled with $^{111}In$. Biodistribution and metabolism study was peformed with two $^{111}In-conjugates$ in mice and rats. Results: $^{111}In-labeled$ T101 and its galactosylated conjugates were taken to the liver by the time, mostly within 10 min. However DTPA conjugate was retained longer in the liver than the 1B4M conjugate (55% vs 20% of injected dose at 44 hr). During this time, the radiornetabolite of DTPA conjugate was excreted similarly into urine (24%) and feces (17%). The radiometabolite of 1B4M was excreted primarily into feces (68%) rather than urine (8%). Size exclusion HPLC analysis of the bile and supernatant of liver homogenate showed two peaks the first (35%) with the retention time (Rt) identical to IgG and the second (65%) with Rt similar to free $^{111}In$ at 3 hr post-injection for the 1B4M conjugate, indicating that the metabolite is rapidly excreted through the biliary system. in contrast to DTPA conjugate, the small $^{111}In-DTPA-like$ metabolite was the major radioindium component (90%) in the liver homogenate as early as 3 hour post-injection, but the cumulative radioindium activity in feces was only 17% at 44 hour, indicating that the metabolite from DTPA conjugate does not clear readily through the biliary tract. Conclusion: The galactosylation of the MoAb conjugates resulted in higher hepatocyte uptake and enhanced metabolism, compared to those without galactosylation. Metabolism of the MoAb-conjugates is different between compounds radiolabled with different chelators due to different characteristics of radiometabolites generated in the liver.

• The Korean Journal of Nuclear Medicine
• /
• v.37 no.6
• /
• pp.393-401
• /
• 2003

Objective: Pullulan derivatives (PD) can be used to make self-assembled hydrogel nanoparticles which are responsive to ionic strength. The aim of this study is to evaluate the potential of PD as a retaining carrier of radioisotope inside tumors. Materials and Methods: Four types of PD were evaluated which included pullulan acetate (PA), succinylated PA (SPA), PA-DTPA and SPA-DTPA conjugates. They were radiolabeled with Tc-99m. Labelling efficiencies were determined at 30 min, 1, 2, 4 and 12 hours after radiolabeling. CT-25 colon cancer cells were subcutaneously injected into Balb/c mice. After 2 weeks of subcutaneous injection, Tc-99m-labelled PD (Tc-99m-PD) were injected into the tumors. Whole body images of mice were obtained at 30 min, 1, 2, and 12 hr after intratumoral injection. All twenty mice were grouped into four groups by largest diameter; control A (largest diameter = 5 mm, n = 5), control B (largest diameter = 10 mm, n = 5), pullulan A (largest diameter = 5 mm, n = 5), pllulan B (largest diameter = 10 mm, n = 5). Dynamic images were obtained for 1 hour after intratumoral injection. Static images were obtained at 1 hr, 2 hr, 3 hr and 4 hr after intratumoral injection with Tc-99m pertechnetate and Tc-99m-PA. Target-to-background ratios and retention rates were calculated. Results: Labeling efficiencies of PA, SPA, PA-DTPA and SPA-DTPA were $94.5{\pm}5.9%,\;97.8{\pm}3.5%\;94.2{\pm}3.8%,\;and\;92.5{\pm}6.2%$, respectively (p>0.05). Percent retention rates (%RR) of PA and PA-DTPA were significantly higher than those of control, however, those of SP-DTPA and SPA became similar to control at 4 and 12 hr, respectively. %RR of pullulan A and pullulan B at 1, 4 and 8 hr is significantly higher than that of control (p < 0.05). However, %RR between pullulan A and pullulan B were similar. Conclusion: The lonic strength dependent PD-nanoparticles are retained in the tumor. No difference of %RR according to tumor size was noted. Therapeutic application of PD labelled with beta- or alpha- emitting radionuclides can be expected.

• The Journal of Korean Academy of Prosthodontics
• /
• v.49 no.3
• /
• pp.254-262
• /
• 2011

Purpose: This study aims to evaluate and prospect for current research trend and developmental perspectives via analyzing recent biomaterial coated-implants study. Materials and methods: To investigate each subject respectively, several biomaterials that are using for implant surface coating were set as 'keywords'. By these keywords, major research groups in each subject were chosen, and research trend of them was analyzed. Trend of In vivo studies that examined selected biomaterials were analyzed to evaluate commercial potential. Results: The collagen research accounted for 40% of total implant study, which was the highest, and fibronectin, BMPs (bone morphogenetic proteins) and RGD (Arg-Gly-Asp) peptides followed, which were ranked in descending order. Furthermore, figures of all four research subjects were also increased with time, especially a sharp increase in RGD research. According to the results of major research group, collagen that was combined with other organic and inorganic biomaterials was mostly examined, rather than using collagen only. Major research groups investigating BMPs mostly focused on rhBMP-2. In animal studies, collagen was used as resorbable membrane in guided bone regeneration (GBR) or drug carrier, while BMPs were used with bone graft materials or coating material for titanium implant surface. Conclusion: There is not consistency of results even in identical subjects research field. Many studies are ongoing to optimize combination between mechanical surface treatment and biomaterials such as extracellular matrix component and growth factors.

• The Korean Journal of Air & Space Law and Policy
• /
• v.25 no.2
• /
• pp.3-42
• /
• 2010

This study shows that the Warsaw Convention in Article 1 is not an international transport, origin, destination and all the Contracting Parties is not a purely domestic shipping does not apply to this Treaty. Therefore, in this case, liability and damages for the governing law is selected according to international law should be. In addition, in the case of international shipping and passenger air carrier of this treaty to govern the relationship, not all of which aim is the unification of certain rules. Product liability is the most important thing of all. As for the aircraft manufacturer's responsibility according to international law also does not select the applicable law is not. The Warsaw Convention Article 17 apply for the passenger's personal damages Article 2 Section 2 leads to the most prestigious type of damages, and subjective and objective with regard to the scope of international law are being committed. In this regard, Governing Law-related aircraft accidents leading to serious accidents in China of an aircraft crash in Nagoya, Japan, the airport can be. China Airlines accident of the aircraft are operated for the unification of the rules for international air transport on the Warsaw Convention as amended by Article 17, Article 18 of damages by the tort claims and claims based on damages caused by, or this cause of aircraft accidents air bus maker by the Corporation for damages in tort claims for damages claimed on the basis of solidarity is the case. In the case of these grand scale claim responsibility for the airline, air transport agreements to determine the applicable law of the contract is very complex. There for the contracts based on individual circumstances or origin, and by considering because each must be determined.

• The Korean Journal of Air & Space Law and Policy
• /
• v.25 no.2
• /
• pp.43-77
• /
• 2010

The development of the aviation industry has exponentially increased the volume of passengers and cargo and gradually expanded the damage scope of all kinds of accidents in the process of transportation. As a result, the need for aviation insurance has accordingly grown bigger and bigger every day. That is why most nations have a law to force mandatory insurance on the aviation industry. However, the Montreal Convention of 1999, which Korea also signed and today has the most extensive effect in the international civil aviation community, offers no clear interpretations about the coverage of aviation insurance along with the Air Transport Business Promotion Act of Korea. The advanced nations of air transport business such as EU, the U. S. A. and Canada prescribe the coverage of aviation insurance and have a law that makes it mandatory for all the passengers and third parties to cover air carrier's liability. EU requires them to include cargo and baggage in scope of coverage, and the U. S. A. and Canada recommend insuring by having a shipper receive a written notice containing information about whether the concerned cargo is insured or not. Making the scope of coverage of aviation insurance clear by law serves several purposes including diversifying risks for air transport companies, providing the victims with enough protection, observing the international accountability required in the air transport industry, and promoting the productive and sustainable growth of the aviation industry. Thus problems with Korea's aviation insurance should be resolved by clearly stating the coverage of aviation insurance that the Korean air carriers and operators need to insure according to the current state of Korea's air transport by consulting the legislations of the advanced nations in air transports. and enacting a law to comprehensively govern Korea's aviation insurance.

• Clinical and Experimental Pediatrics
• /
• v.49 no.12
• /
• pp.1340-1347
• /
• 2006

Purpose : The aim of the present study was to investigate the role of polymorphic cytosine adenine (CA) repeat of the IGF-I gene in the age-related alterations of serum IGF-I levels in healthy children. Methods : Two hundred and forty three normal healthy children (136 boys; 107 girls) aged between 7 and 15 years were enrolled in the present study. The primers were designed to cover the promoter regions containing the polymorphic CA repeat. Data were analyzed using GeneMapper software, version 3.7. All analyses were performed using MEDCALC software packages. Results: Deletion of 2 bp (G, A) following 3' of CA repeat were observed in all Korean children. The CA repeat sequences ranged from 17 to 23, and 19 CA repeat were the most common with an alleles frequency of 39.3 percent. Considering genotypes, 63.8 percent of subjects were homozygote or heterozygote for 19 CA repeat (192 bp allele), suggesting that this is wild type allele from which all other alleles originated in Korean children. Homozygote for 19 CA repeat were 14.7 percent, heterozygote for 19 CA repeat was 49.1 percent and 19 CA noncarriers totalled 36.2 percent. In 19 CA repeat noncarriers, the mean height, weight and serum IGF-I level were lower compared with those of 19 CA homozygous carriers, but statistically not significant. Correlations between serum IGF-I level and age according to the IGF-I genotypes revealed statistically significant relationships in the all groups, in the 19 CA repeat carrier group and, even in the noncarrier group. Conclusions : There were no significant differences of the mean height, weight and serum IGF-I levels among three different genotype groups. Also, there were no significantly different correlations between 19 CA repeat polymorphisms and serum IGF-I levels, according to genotype. Our results suggest that the IGF-I 19 CA repeat gene polymorphism is not associated with circulating IGF-I levels in healthy children.

• The Journal of the Korean Society for Microbiology
• /
• v.17 no.1
• /
• pp.67-74
• /
• 1982

Staphyylococci are responsible for over 80 per cents of the suppurative diseases encountered in medical practice. They cause most suppurative infections of the skin but may also invade and produce severe infections in any other parts of the body. In order to know the carrier rate of staphylococci between the parahospital workers and in the hospital workers, the author undertook isolation of S aureus from nasal cavity on 68 cases of freshmen, 31 cases of sophomores, and 37 cases of juniors in Busan National University, and 30 cases of nursing students, 30 cases of nurses, 30 cases of nurses in charge of operating room and 30 cases of doctors in Busan National University Hospital. The tested total cases were 256 cases which were 136 Cases in parahospital workers and which were 120 cases in hospital workers. The biochemical characters of S aureus strains isolated were studied on coagulase test, mannitol test, hemolysis test and sensitivity test to antimicrobial agents. The results obtained were as follows: 1. S aureus were isolated 49 cases(29.7%) from nasal cavity parahospital workers and were isolated 67 cases(55.8%) from nasal cavity on hospital workers. 2. Among 40 strains of S aureus isolated from parahospital worker's nasal cavity coagulase positive were 29 cases(72.1%), and coagulase negative were 11 cases(27.5%). And mannitol positive were 29 cases(72.5%), and mannitol negative were 11 cases(27.5%). 3. Among 67 strains of S aureus isolated from hospital worker's nasal cavity coagulase positive were 59 cases(88.1%), and coagulase negative were 8 cases(11.9%). And mannitol positive were 49 cases(73.1%), and mannitol negative were 18 cases(26.9%). 4. The hemolysis test of each erythocytes on coagulase and mannitol positive S aureus isolated were sensitive to rabbit(40 cases: 81.6%), guinea pig(26 cases: 53.6%), sheep(13 case: 26.5%), and were not sensitive to chicken and human erythrocytes, respectively. 5. The hemolysis test of each erythocytes on 10 strains of coagulase and mannitol negative S aureus isolated were not sensitive to all of, erythrocytes. 6. The sensitivity test to the various chemotherapeutic agents was almost sensitive to the strains isolated from parahospital workers, but was almost resistant to the strains isolated from hospital workers.

• Applied Biological Chemistry
• /
• v.26 no.4
• /
• pp.222-230
• /
• 1983

This study was designed to develop a process for the immobilization of xylose isomerase(D-xylose ketol isomerase, EC 5.3.1.5) from Streptomyces griseolus previously isolated by the authors and its application on a pilot plant scale for the production of high fructose corn syrup. The biomass which has endo-excreted xylose isomerase was homogenized under a pressure of $500kg/cm^2$ and 90.8% of the enzyme recovery of the native activity was obtained as compared to 54.7% recovery by the lysozyme treatment. Ionic bonding method was adopted for the enzyme immobilization due to its many reported merits. It was found that the porous resins such as Diaion HP 20, Duolite A-7, Amberlite IRA 93 and 94 were effective in immobilizing the enzyme. In addition, it was disclosed that the regeneration form of $BO_4--$ is effective for Amberlite IRA 93 and $HCO_3-$ for Diaion HP 20. Optimal immobilization condition for Amberlite IRA 93 was pH 8.0 and $55^{\circ}C$ yielding 80.6% of immobilization. Activity decay test showed half life of the immobilized enzyme with Amberlite IRA 93 was more than 24 days at $65^{\circ}C$. The carrier was evaluated to be resuable and its result showed the relative immobilization yields were 98.2, 93.3, 90.7 and 87.5%, respectively at second, third, forth and fifth rebinding test of the enzyme on Amberlite IRA 93. Optimal temperature of the immobilized enzyme was slightly lowered and the range widened to $60\sim70^{\circ}C$, while optimal pH moved toward $8.0\sim8.3$ in its isomerization reaction. The trial production result of high fructose corn syrup in pilot scale immobilization showed that one liter of immobilized xylose isomerase (350 IXIU/ml-R) is capable producing about 293l high fructose corn syrup(75% dry substance) in 30 days.

• Clinical and Experimental Pediatrics
• /
• v.45 no.3
• /
• pp.302-310
• /
• 2002

Purpose : X-linked agammaglobulinemia(XLA) is an immunodeficiency caused by abnormalities in Bruton's tyrosine kinase(Btk), and is characterized by a deficiency of peripheral blood B cells. We studied cytoplasmic expression of Btk protein and analyzed the Btk gene in peripheral blood mononuclear cells(PBMC) from three XLA families in Korea. Methods : Heparinized venous blood samples were collected from four XLA patients and additional family members in three unrelated XLA families. Mononuclear cells were separated from their blood and the intracellular Btk protein was characterized by a flow cytometry. The mutation analysis was performed using direct sequencing. Results : Cytoplasmic expression of Btk protein in monocytes was not detected in the patients with XLA. We observed a novel deletion and two point mutations within introns(intron 1 and intron 18) resulting in alternative splicings. In XLA family 2, a 980 bp deletion(from intron 9+191 T to intron 10-215 C) including exon 10 was found in patient P2. He was the only sporadic case in this study, because his mother and brother showed a normal Btk expression by flow cytometry. Conclusion : These identified genetic alterations support the molecular heterogeneity of Btk gene in XLA disease. Additionally, by means of flow cytometric analysis, we diagnosed three hypogammaglobulinemia patients as XLA. Advancements in diagnostic methods has facilitated a prompt and definite diagnosis of this disease.