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Biomedical subjects

C G Kim

Publications and source records attributed to C G Kim.

At least 19 recordsLinked to original sources

Drug-protein interaction with Vpu from HIV-1: proposing binding sites for amiloride and one of its derivatives.

Vpu is an 81-amino-acid auxiliary protein of the genome of HIV-1. It is proposed that one of its roles is to enhance particle release by self-assembling to form water-filled channels enabling the flux of ions at the site of the plasma membrane of the infected cell. Hexamethylene amiloride has been shown to block Vpu channel activity when the protein is reconstituted into lipid bilayers. In a docking approach with monomeric, pentameric and hexameric bundle models of Vpu corresponding to the transmembrane part of the protein, a putative binding site of hexamethylene amiloride is proposed and is compared with the site for the nonpotent amiloride. The binding mode for both ligands is achieved by optimizing hydrogen bond interactions with serines. Binding energies and binding constants are the lowest for protonated hexamethylene amiloride in the pentameric bundle.

Amiloride↗

Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic gastric carcinoma.

The current treatment for metastatic gastric cancer (MGC) consists of cisplatin and/or fluorouracil (5-FU) based combination chemotherapy, but cisplatin-based regimens are associated with considerable toxicity. We evaluated the efficacy and safety of a noncisplatin-, non-5-FU-containing regimen, docetaxel/irinotecan in MGC. Chemo-naive patients with MGC received docetaxel (30 mg m(-2)) and irinotecan (70 mg m(-2)) on days 1 and 8 every 3 weeks. The 48 eligible patients (median age 56 years) received a median of four cycles of docetaxel/irinotecan (range 1-18). Of the 46 patients in whom efficacy could be evaluated, 21 showed a partial response (response rate=45.7%; 95% confidence interval (CI) 31.3-60.1%). At a median follow-up of 15.0 months, the median time to progression was 4.5 months (95% CI 3.8-5.2 months) and overall survival was 8.2 months (95% CI, 5.8-10.6 months). Grade 3/4 neutropenia developed in 57.4% of patients, and febrile neutropenia/neutropenic infection in 19.1%. Nonhaematological toxicities were moderate; grade 3/4 diarrhoea occurred in 19.1% of patients, however, was manageable by a dose reduction. There was one possible treatment-related death. In conclusion, weekly docetaxel/irinotecan is a promising outpatient regimen in MGC, with appropriate dose modification.

Adenocarcinoma↗

Comparative study of the subserosal versus submucosal dye injection method for sentinel node biopsy in gastric cancer.

AIMS: To determine the most efficient injection method for a sentinel node (SN) biopsy in gastric cancer. METHODS: Gastric adenocarcinoma patients without serosal invasion and distant metastasis were prospectively enrolled in this study. Isosulfan blue was injected into the subserosa (SS) of the first set of 71 consecutive patients and an intraoperative endoscopic submucosal (SM) injection of the same dye was injected into the second set of 50 consecutive patients. After the biopsy of blue-stained SNs, a gastrectomy with a D2 lymphadenectomy was performed. All dissected lymph nodes were evaluated for metastasis. The results of the SN biopsies were compared between the SS and SM dye injection methods. RESULTS: Detection rate (0.92 vs 0.94), mean number of SNs (2.5 vs 2.9) and sensitivity (0.61 vs 0.46) of the SN biopsies were not significantly different between the SS and SM injection methods (P>0.05). The operation time was significantly shorter in the SS than the SM injection method (159.7 vs 172.7 min, P=0.030). CONCLUSIONS: Both injection methods were equally efficient in their roles for a SN biopsy in gastric cancer. However, the SS injection method was more preferable due to its easy technique and short operation time.

Adenocarcinoma↗

The role of hand-assisted laparoscopic distal gastrectomy for distal gastric cancer.

BACKGROUND: The aim of this study was to evaluate the role of hand-assisted distal gastrectomy (HALDG) for gastric cancer. METHODS: This study prospectively enrolled 16 patients who underwent HALDG for early gastric cancer and matched them individually by sex, age, and body mass index to patients who underwent laparoscopically assisted distal gastrectomy (LADG) or open distal gastrectomy (ODG). Surgical outcomes were compared among the surgical methods. RESULTS: The mean operating time was the longest for the HALDG group, whereas wound size of the HALDG group was intermediate between that of the LADG and the ODG groups. The other surgical outcomes, such as the number of harvested lymph nodes, were not different among the groups. CONCLUSIONS: According to the findings, HALDG may not be as beneficial for patients with early gastric cancer as has been previously suggested. However, because of easier hand-eye coordination, HALDG may be an excellent bridge learning technique as a surgeon gains experience in laparoscopic gastrectomy.

Adult↗

Interaction of amiloride and one of its derivatives with Vpu from HIV-1: a molecular dynamics simulation.

Vpu is an 81-residue membrane protein, with a single transmembrane segment that is encoded by HIV-1 and is involved in the enhancement of virion release via formation of an ion channel. Cyclohexamethylene amiloride (Hma) has been shown to inhibit ion channel activity. In the present 12-ns simulation study a putative binding site of Hma blockers in a pentameric model bundle built of parallel aligned helices of the first 32 residues of Vpu was found near Ser-23. Hma orientates along the channel axis with its alkyl ring pointing inside the pore, which leads to a blockage of the pore.

Amiloride↗

Nitrification and denitrification using a single biofilter packed with granular sulfur.

This study was performed to develop a granular sulfur packed nitrification/denitrification process employing a uniquely designed single biofilter, which treated a relatively low carbon loaded domestic wastewater taken from a primary clarifier at a municipal wastewater treatment facility. The system was tested on varying experimental conditions, e.g. inflow flow, organic load and nitrogen load. Regardless of flow rate being increased, SS and COD was unvaryingly removed up to 90 and 80%, respectively. Moreover, TKN was also decomposed up to 90%. Increase in COD load gradually led to escalating level of non-biodegradable compounds observed in effluent. Nitrification was accomplished as high as 92%, whereas denitrification was achieved up to approximately 87%. For a while, nitrification and denitrification were observed at 0.65 and 0.55 kg/m3 x day, respectively. Eventually, T-N was decomposed as high as 46%. It was concluded that granular sulfur can be used for not only electron donor, but also for a media to properly treat low carbon loaded wastewater and to filter SS efficiently.

Biodegradation, Environmental↗

The complete DNA sequence of the mitochondrial genome of the self-fertilizing fish Rivulus marmoratus (Cyprinodontiformes, Rivulidae) and the first description of duplication of a control region in fish.

We isolated Rivulus marmoratus mitochondrial DNA by long-polymerase chain reaction with conserved primers, and sequenced it with 36 sets of internal conserved primers, which were designed from the extensive sequence similarities of mitochondrial DNA from several fish species. The R. marmoratus mitochondrial DNA has 17,329 bp with a conserved structural organization compared to those of other fish. Rivulus marmoratus mitochondrial DNA also has two nearly identical control regions. The basic characteristics of the R. marmoratus mitochondrial genome are discussed.

Animals↗

Genomic cloning of the Hsc71 gene in the hermaphroditic teleost Rivulus marmoratus and analysis of its expression in skeletal muscle: identification of a novel muscle-preferred regulatory element.

To further our understanding of the role of stress proteins in development as well as in adaptation of fish to adverse environmental conditions, we undertook molecular analyses of stress protein encoding genes from the hermaphroditic teleost Rivulus marmoratus. We isolated a genomic clone containing the Hsc71 gene (rm-hsc71m) and its upstream sequences. rm-Hsc71m is not induced by external stress, but is enriched in a tissue-specific manner during early development. In adult, the strongest expression appeared in skeletal muscle, whereas lower expression was seen in the gill, eye and brain. To understand the regulatory basis of high muscle expression of rm-hsc71m, transfection of R.marmoratus muscle tissue was performed using 5' deletion fragments containing the rm-hsc71m promoter driving EGFP expression. An upstream region from -2.7 to -1.9 kb was identified as a muscle-specific regulatory region. Within this region, we identified at least three sites with the novel sequence TGTnACA interacting with a fish muscle factor having an M(r) of 32 000. Our data indicate that rm-hsc71m expression in skeletal muscle is controlled by a muscle-specific regulatory element containing this novel motif.

Animals↗

Mutational analysis and reconstituted expression of the biosynthetic genes involved in the formation of 3-amino-5-hydroxybenzoic acid, the starter unit of rifamycin biosynthesis in amycolatopsis Mediterranei S699.

To investigate a novel branch of the shikimate biosynthesis pathway operating in the formation of 3-amino-5-hydroxybenzoic acid (AHBA), the unique biosynthetic precursor of rifamycin and related ansamycins, a series of target-directed mutations and heterologous gene expressions were investigated in Amycolatopsis mediterranei and Streptomyces coelicolor. The genes involved in AHBA formation were inactivated individually, and the resulting mutants were further examined by incubating the cell-free extracts with known intermediates of the pathway and analyzing for AHBA formation. The rifL, -M, and -N genes were shown to be involved in the step(s) from either phosphoenolpyruvate/d-erythrose 4-phosphate or other precursors to 3,4-dideoxy-4-amino-d-arabino-heptulosonate 7-phosphate. The gene products of the rifH, -G, and -J genes resemble enzymes involved in the shikimate biosynthesis pathway (August, P. R., Tang, L., Yoon, Y. J., Ning, S., Müller, R., Yu, T.-W., Taylor, M., Hoffmann, D., Kim, C.-G., Zhang, X., Hutchinson, C. R., and Floss, H. G. (1998) Chem. Biol. 5, 69-79). Mutants of the rifH and -J genes produced rifamycin B at 1% and 10%, respectively, of the yields of the wild type; inactivation of the rifG gene did not affect rifamycin production significantly. Finally, coexpressing the rifG-N and -J genes in S. coelicolor YU105 under the control of the act promoter led to significant production of AHBA in the fermented cultures, confirming that seven of these genes are indeed necessary and sufficient for AHBA formation. The effects of deletion of individual genes from the heterologous expression cassette on AHBA formation duplicated the effects of the genomic rifG-N and -J mutations on rifamycin production, indicating that all these genes encode proteins with catalytic rather than regulatory functions in AHBA formation for rifamycin biosynthesis by A. mediterranei.

Actinomycetales↗

Effects of simultaneous kidney-pancreaticoduodenal transplantation on diabetes-induced renal insufficiency in rats.

An investigation of the functional and histological changes was done after en-bloc kidney-pancreaticoduodenal transplantation (kpdt) in the diabetes-induced, renal insufficient Lewis rats. For donor preparation, an end-to-side portocaval shunt was performed, and the aortic, vena caval segments, and ureter-bladder patch were obtained. They were anastomosed microsurgically to recipient's aorta, vena cava, and bladder in end-to-side fashion. Of 15 diabetes-induced kpdt rats, 14 survived. Two of the 14 surviving rats showed ischemic necrosis. The remaining 12 transplants showed well-preserved glomeruli and Langerhans islets for 5 months postoperatively. Biochemical data comparing diabetic and sham-operated rats (six rats each), six diabetic controls, and 12 kpdt rats showed no significant statistical difference at said observation period. The diabetes-induced kpdt rats showed improvement of following biochemical data: within 1 week postoperatively, the glucose level fell from 300 to 115 mg/dL; BUN level from >20 to <20 mg/dL; the creatinine level from 1.5 to <1.2 mg/dL. The insulin level returned to normal, 1.1 ng/mL, in 2 weeks. The results demonstrate that the kpdt model is an effective and successful operative technique in diabetic rats and may provide effective therapeutic methods for diabetes-induced renal insufficiency.

Animals↗

T-Cell type acute lymphoblastic leukemia following cyclosporin A therapy for aplastic anemia.

Cyclosporin A (CsA) is used to prevent rejection in transplantation and to treat autoimmune and hematologic diseases such as aplastic anemia. However, the tumor growth-promoting effect of CsA remains controversial. We report the case of a 24-year-old man who developed acute lymphoblastic leukemia of precursor-T-cell origin after 75 months of treatment with CsA for aplastic anemia. The surface antigen phenotype of his leukemic cells was CD2+, CD3+, CD5+, CD7+, CD4-, CD8-, CD10-, CD20-, CD34-, CD41-, and CD56-. Southern blot analysis revealed a monoclonal rearrangement of T-cell receptor-Jgamma nongermline fragments in HindIII digestion.

Adolescent↗

Dramatically accelerated growth and extraordinary gigantism of transgenic mud loach Misgurnus mizolepis.

Transgenic mud loaches (Misgurnus mizolepis), in which the entire transgene originated from the same species, have been generated by microinjecting the mud loach growth hormone (mlGH) gene fused to the mud loach beta-actin promoter. Out of 4,100 eggs injected, 7.5% fish derived from the injected eggs showed dramatically accelerated growth, with a maximum of 35-fold faster growth than their non-transgenic siblings. Many fast-growing transgenic individuals showed extraordinary gigantism: their body weight and total length (largest fish attained to 413 g and 41.5 cm) were larger and longer than even those of 12-year-old normal broodstock (maximum size reached to 89 g and 28 cm). Of 46 transgenic founders tested, 30 individuals transmitted the transgene to next generation with a wide range of germ-line transmission frequencies ranging from 2% to 33%. The growth performance of the subsequent generation (F1) was also dramatically accelerated up to 35-fold, although the levels of enhanced growth were variable among transgenic lines. Three transgenic germ-lines up to F4 were established, showing the expected Mendelian inheritance of the transgene. Expression of GH mRNA in many tissues was detected by RT-PCR analyses. The time required to attain marketable size (10 g) in these transgenic lines was only 30-50 days after fertilization, while at least 6 months in non-transgenic fish. Besides growth enhancement, significantly improved feed-conversion efficiency up to 1.9-fold was also observed.

Actins↗

The comparative selection between spiral wound and disc tube membranes to treat steel industry wastewater.

To select the most suitable membrane process to treat the final effluent discharged from the S wastewater treatment facility at P Steel Works, the effluent was passed through two types of membrane (spiral wound and disc tube) in a pilot-scale study. The permeate flux and regeneration of each membrane were comparatively observed and the removal efficiency of contaminants determined. The experimental results from employing the disc tube membrane revealed that the fouling was comparably limited by operating the plant at 34 bar recovery and was highly sustained at permeate flux of 75% which equals to 32.9 l/hr.m2. In contrast, the fouling was significantly greater when applying the spiral would membrane with the recovery correspondingly diminished at 72%. The disc-tube membrane was chosen to treat the effluent to be recycled for process water as the water quality satisfied the industry water standards.

Equipment Design↗

[Marginal zone lymphoma associated with Sjögren's syndrome and hepatitis C virus infection].

A 64-year-old female was admitted in May 1997, because of salivary gland swelling. Histology of the right parotid gland revealed malignant lymphoma, diffuse medium-sized B-cell type, and she was treated with local radiotherapy and chemotherapy. She was rehospitalized in April 1998, because of recurrence of lymphoma in the stomach and the sigmoid colon. She had splenomegaly and lymphadenopathy (neck and inguinal). Laboratory findings revealed marked elevation of rheumatoid factor and RNA of hepatitis C virus. A diagnosis of Sjogren's syndrome was made by dryness and the histological findings of labial biopsy. Marginal zone B-cell lymphoma mainly consisted of centrocyte-like cells and lymphoepithelial lesions, and CD 20 and IgM-kappa were positive with immunohistochemical staining. Lymphoma involved the gut and spleen. We discuss the correlation of malignant lymphoma with Sjogren's syndrome and HCV infection.

Antigens, CD20↗

Systemic lupus erythematosus presenting earlier as retinal vaso-occlusion.

Retinal vascular lesions are the most common ophthalmologic manifestation of systemic lupus erythematosus (SLE), occurring in 3% to 29% of cases, generally late in the disease. More rare is the severe vaso-occlusive disease, often termed "retinal vasculitis", which includes central retinal artery occlusion, multifocal arteriolar occlusions, extensive capillary nonperfusion and central venous occlusion. Patients with SLE and raised serum concentrations of anticardiolipin antibodies (ACA) have a higher risk of developing occlusive ocular vascular disease. We report a case in which retinal involvement was an earlier manifestation of SLE in a patient without ACA.

Adolescent↗

[A case of Sjögren's syndrome with dermatomyositis who died of rapidly progressive interstitial pneumonia].

We report a case of 55 year-old woman with six year history of Sjögren's syndrome developed fatal rapidly progressive interstitial pneumonia. She had been well until February 1999. She developed swelling and erythematous lesions in the cheek and hands in spring 1999. She was admitted to our hospital for investigations of skin lesions in May 1999. Physical examination on admission revealed small hemorrhagic lesions in the nailfold. Serum CK level was slightly elevated. Electromyogram and MRI suggested mild myositis in the proximal upper extremities. She was suspected to have dermatomyositis along with Sjögren's syndrome. Prednisolone 10 mg/day had been given for her skin problems since March 1999. Suddenly, dyspnea on exertion was appeared on 34th day of admission. Chest X-ray film showed an acute worsening of interstitial pneumonia. Methylprednisolone pulse therapy (1000 mg for 3 days) and cyclophosphamide pulse therapy (500 mg for a day) were started, and she was subsequently treated with 60 mg/day of prednisolone and 250 mg/day of Cyclosporin A. However, interstitial pneumonia did not respond to the treatment, and pneumomediastinum and pneumothorax have developed. She died of respiratory failure on 55th day. We consider that most likely explanation for fatal interstitial pneumonia is concomitantly occurred dermatomyositis.

Cyclophosphamide↗

p16 is a major inactivation target in hepatocellular carcinoma.

BACKGROUND: The p16(INK4A) gene encodes 2 cell cycle regulator proteins, p16 and p14(ARF), by alternative splicing. This genetic locus also contains another cell cycle regulator gene, p15(INK4B), which encodes p15. The inactivation of the p16 protein has been demonstrated in some hepatocellular carcinomas (HCCs); however, the inactivation of the other 2 cell regulator proteins and their inactivation patterns are not well characterized. METHODS: To characterize the role of the above 3 cell cycle regulator proteins in HCCs, the authors examined the genomic status of the p16(INK4A) and p15(INK4B) genes and their RNA products in 20 HCC tissues and 7 human HCC cell lines. Homozygous deletions in each exon of p16(INK4A) and p15(INK4B) were evaluated by comparative multiplex polymerase chain reaction (PCR), and the methylation status of the p16(INK4A) and p15(INK4B) promoter region was analyzed by methylation specific PCR. RESULTS: Homozygous deletions were found in 6 of 20 HCCs (30%) and 2 of 7 HCC cell lines (29%). In 20 HCCs, the frequency of homozygous deletions was 20% in exon 1 of p15(INK4B), 20% in exon 2 of p15(INK4B), 10% in exon 1beta of p16(INK4A), 25% in exon 1alpha of p16(INK4A), 15% in exon 2 of p16(INK4A), and 15% in exon 3 of p16(INK4A). The authors found hypermethylation of the p16(INK4A) promoter region in 7 HCCs (35%) and 3 HCC cell lines (43%). The overall frequency of p16 alterations in HCCs, including hypermethylation and homozygous deletions, was 60% (12 of 20 cases). According to reverse transcriptase-PCR analysis, the absence of RNA expression was most frequent in p16 (11 of 20 cases, 55%) and less frequent in p15 (7 of 20 cases, 35%) and p14(ARF) (5 of 20 cases, 25%). CONCLUSIONS: Among the 3 cell cycle regulator proteins encoded at the 9p21 genetic locus, inactivation of p16 is the most frequent event in HCCs in which promoter hypermethylation and homozygous deletions are the common mechanisms.

Carcinoma, Hepatocellular↗