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ABSTRACT: TNF-alpha promoter polymorphism is known to play an important role in the immunopathogenesis of infection of hepatitis B virus.
We investigated whether polymorphisms of TNF-alpha promoter at position -308 or -238 had associations with the response to lamivudine treatment.
A total of 89 healthy subjects (control group) and 225 patients with chronic hepatitis B treated with lamivudine were included in this study. Polymorphisms of TNF-alpha promoter at position -308 and -238 were analyzed by polymerase chain reaction. Recruited patients were classified according to the outcome of lamivudine treatment into the responder (103 patients) or non-responder (122 patients) group.
The numbers of A allelic polymorphism of TNF-alpha promoter at position -238 were four (2.2%) in the control, five (2.4%) in the responder and 19 (7.8%) in the non-responder group. The A allele was noted significantly more frequently in the responder than non-responder group (P = 0.012). At position -308, a significant difference was observed between the control group (14; 7.9%) and total chronic hepatitis B patients (15; 3.3%) (P = 0.015).
Our study demonstrated that the non-response to lamivudine treatment in patients with chronic hepatitis B might be related to the A allelic polymorphism of TNF-alpha promoter at position -238.
Digestive Diseases and Sciences 10/2009; 55(7):2043-8. · 2.12 Impact Factor
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ABSTRACT: High-dose chemotherapy supported by autologous stem cell transplantation (ASCT) after combined chemotherapy with infusional vincristine/doxorubicin plus dexamethasone is effective in multiple myeloma (MM). Outpatient treatment with bolus vincristine/doxorubicin infusion plus dexamethasone is convenient and has acceptable efficacy and toxicity for MM. Thalidomide has recently been shown to have significant antimyeloma activity. We assessed the efficacy and toxicity of the combination of bolus vincristine/doxorubicin and reduced dose dexamethasone with thalidomide (T-bVAd), administered on an outpatient basis, in untreated MM.
Twenty-six patients prospectively received T-bVAd, consisting of intravenous (i.v.) vincristine 0.4 mg plus doxorubicin 9 mg/m(2), administered as a single bolus on days 1 to 4, dexamethasone 20 mg per os daily for 4 days, and thalidomide 200 mg/day at bedtime. Response assessment was conducted after each 4-week treatment cycle. Patients who achieved response were allowed to proceed to high-dose chemotherapy with ASCT.
On an intention-to-treat basis, 23 of the 26 patients (88%) responded to treatment, with 16 (61%) achieving complete response (CR), 2 (8%) very good partial response (VGPR) and 5 (19%) partial response. Only three patients (12%) were rated as non-responders. Grade 3 and 4 hematologic toxicities consisted of neutropenia (13%), febrile neutropenia (6%), and thrombocytopenia (4%), without significant nonhematologic events. Of the 23 patients who showed response, 7 proceeded to single ASCT and 9 to tandem ASCT. With median follow-up time of 15.3 months (range, 9-25 months), median event free survival (EFS) and overall survival (OS) have not been reached yet, and OS and EFS rates for patients who achieved complete response after T-bVAd regimen were significantly higher than patients not.
Induction therapy with T-bVAd, administered as an outpatient regimen, was efficient and relatively well tolerated in the treatment of MM.
Investigational New Drugs 10/2009; 29(1):175-81. · 3.36 Impact Factor
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ABSTRACT: : The fluoroscopic imaging technique that has been used in the dorsal percutaneous screw fixation of scaphoid fracture was modified for more consistent central screw placement according to the different fracture locations.
: Eighteen scaphoids of the fresh-frozen cadaver were used. The computed tomographic data of scaphoid were reconstructed for 3D images. The reconstructed image was three dimensionally rotated to define the outlining images of scaphoid according to the three imaginary fracture lines (proximal 1/3, waist, distal 1/3). Two dimensional plain radiographic images were taken based on the 3D image to show the overlapping shapes of outer cortical lines of proximal and distal scaphoid. Under the fluoroscopic guidance, guide wire was inserted after the previously obtained 2D images. To verify the accuracy of fluoroscopic guidance for the fixation, the scaphoid was cut through each fracture plane and central position of each guide wire was analyzed.
: For the proximal 1/3 fracture, the proximal cortical line was positioned on the radial side to the distal cortical line. For the waist fracture, two cortical shadows were eclipsed and for the distal 1/3, proximal cortical line was positioned ulna side to the distal cortical line. The cut surface analysis revealed statistically significant results of central guide wire placement for each fracture plane.
: The fluoroscopic images should be individualized according to the fracture planes for more consistent and accurate central guide wire placement in the dorsal percutaneous screw fixation of scaphoid fracture.
The Journal of trauma 10/2009; 68(3):616-9. · 2.48 Impact Factor
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ABSTRACT: In this study, we prepared a blended nanofiber scaffold using synthetic and natural polymers, polyurethane (PU) and gelatin respectively, using the electrospinning method to prepare a material for wound dressing. In order to confirm the properties of this gelatin/PU blended nanofiber scaffold, we performed scanning electron microscopy, atomic force microscopy, attenuated total reflectance Fourier-transform infrared spectroscopy, thermal gravimetric analysis, contact angle, water uptake, mechanical property, recovery, and degradation tests, and cellular response. The results obtained indicate that the mean diameter of these nanofibers was uniformly electrospun and ranged from 0.4 to 2.1 microm. According to the results, when the amount of gelatin in the blended solution decreased, the contact angle increased and water uptake of the scaffold decreased concurrently. In the mechanical tests, the blended nanofibrous scaffolds were elastic, and elasticity increased as the total amount of PU increased. Moreover, as the total amount of gelatin increased, the cell proliferation increased with the same amount of culture time. Therefore, this gelatin/PU blended nanofiber scaffold has potential application for use as a wound dressing.
Biomedical Materials 09/2009; 4(4):044106. · 2.16 Impact Factor
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ABSTRACT: To assess the dependence on age of the expression of apoptosis regulatory proteins in the human semitendinosus muscle, we measured the expression levels of several apoptosis-related genes, including apoptosis-inducing factor (AIF), Bax, Bcl-2, caspase-3 and heat shock protein 70 (HSP70), using RT-PCR, immunohistochemistry and TUNEL assays. We found that the DNA fragmentation was proportional to the age of the tissues sample donors. The expression levels of AIF were significantly elevated (by 10 to 25%) in semitendinosus tissue samples from older individuals, but the Bax, Bcl-2, caspase-3 and HSP 70 levels remained almost constant. This data suggests that the morphological and functional changes observed in aged human semitendinosus muscle correlates with the apoptosis of muscle cells through the induction of AIF.
Cellular & Molecular Biology Letters 09/2009; 15(1):1-12. · 1.50 Impact Factor
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ABSTRACT: Histone deacetylase inhibitors (HDACIs) are potent anticancer drugs, and suberoylanilide hydroxamic acid is used for the treatment of cutaneous T-cell lymphoma patients. We synthesized a novel hydroxamate-based HDACI, CG0006, and assessed its antiproliferative effects on the NCI-60 cancer cell panel and cell lines from liver and stomach cancers that are common in Korea. Micromolar levels of CG0006 induced cell death in several breast, central nervous system, colon, hematopoietic, lung, melanoma, ovarian, prostatic, renal, and stomach cancer cell lines. We further analyzed cell death mechanisms activated by CG0006 in HCT116 (colon cancer) and K562 (leukemia) cells. First, to test the activity of CG0006, we analyzed acetylation of substrates of HDACs and effect on gene expression. CG0006 increased acetylation of histone 3, histone 4, and tubulin in a time-dependent and dose-dependent manner in both HCT116 and K562 cells. Moreover, CG0006 increased the mRNA level of p21 and decreased that of Bcl-xl efficiently in HCT116 cells. Cell cycle analysis showed G2-M arrest, and increased apoptosis in populations of HCT116 and K562 cells treated with CG0006. Western blot analysis showed that CG0006 increased levels of p21 in HCT116 cells and of p21 and p27 in K562 cells. In addition, CG0006 activated caspase-9, caspase-3, and caspase-8. These results indicate that CG0006 induces death in HCT116 and K562 cells through both intrinsic and extrinsic apoptotic pathways. The HDACI CG0006 may be a potent anticancer drug for solid tumors and leukemia.
Anti-cancer drugs 08/2009; 20(9):815-21. · 2.23 Impact Factor
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ABSTRACT: It has been suggested that mitochondrial dysfunction contributes to the initiation and development of atherosclerosis and cardiovascular disease. We examined the association between mitochondrial DNA (mtDNA) copy number and microalbuminuria in a cross-sectional community-based study. We measured peripheral blood mtDNA copy number in 694 adults without chronic kidney disease by a real-time PCR method. The overall prevalence of microalbuminuria (defined as an albumin creatinine ratio of 30 to 299 mg/g) was 4.5%. The prevalence of microalbuminuria decreased progressively from the lower to the upper quartiles of mtDNA copy number (6.9%, 5.7%, 2.9%, and 2.3% in quartiles 1, 2, 3, and 4, respectively, P=0.017 for trend). Multiple logistic regression models showed that the quartile of mtDNA copy number was independently associated with the prevalence of microalbuminuria (P=0.01 for trend). Compared with the lowest quartile, the highest quartile had an odds ratio of 0.22 for microalbuminuria (95% confidence interval, 0.05 to 0.87; P=0.03). Higher mtDNA copy number was associated with the lower prevalence of microalbuminuria in a community-based population.
Experimental and Molecular Medicine 04/2009; 41(4):253-8. · 2.48 Impact Factor
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ABSTRACT: This study was to evaluate the efficacy of histone deacetylase (HDAC) inhibitors in colorectal cancer together with other established regimens.
Chemosensitivities of 114 colorectal cancer patients to established regimens (fluorouracil (5-FU with leucovorin (FL), capecitabine, FL with irinotecan (FLIRI), and FL with oxaliplatin (FLOX)) as well as five hydroxamic acid derivatives (suberoylanilide hydroxamic acid, PXD101, and three novel candidates of CG-1, CG-2, and CG-3) were comparatively evaluated using the histoculture drug response assay.
The chemosensitivity with established regimens was between 34.2% and 52.6%, when the cutoff value of the inhibition ratio was set at 30%, and between 54.5% and 84.1% with HDAC inhibitors. All HDAC inhibitors displayed synergistic effects in combination with established regimens of FLOX and FLIRI (P < or = 0.0001-0.002). Advanced T- and N-category tumors and patients with synchronous adenoma displayed higher chemosensitivity to CG-3, CG-2, and CG-1, respectively, on a multivariate analysis (P = 0.023, 0.044, and 0.045, respectively). Tumors with mismatch repair defects were closely correlated with chemosensitivities to combined regimens of PDX101 with FLOX and FLIRI (P = 0.044 and 0.048, respectively).
Our findings firstly demonstrated the chemo-responsiveness of colorectal cancers to HDAC inhibitors with therapeutic efficacy comparable to the established regimens. Additionally, tumor growth and heredity were significantly associated with specific regimens, supporting their possible role as chemosensitive predictors.
International Journal of Colorectal Disease 10/2008; 24(2):209-18. · 2.38 Impact Factor
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ABSTRACT: Carbonic anhydrase (CA) is a zinc metalloenzyme that participate in the biological processes of various fluid transporting epithelia, including ion and water transport. CA may thus play a role in the pathophysiology of normal nasal mucosa and nasal polyp. We evaluated the expression and pattern of distribution of mRNAs and proteins for CA isoenzymes in normal nasal mucosa and polyps.
This was a controlled, prospective study.
The expression levels of 11 isoenzyme genes (I, II, III, IV, VA, VB, VI, VII, IX, XII, XIV) were evaluated in normal mucosa and polyps using semiquantitative reverse-transcriptase polymerase chain reaction. The expression and pattern of distribution of CA I, II, and IX were also investigated using immunohistochemistry and Western blot.
mRNAs for the 11 CA isoenzymes were detected in all normal nasal mucosa and polyps tested. Their expression levels were decreased in nasal polyp in comparison with normal nasal mucosa. CA I was detected in the epithelial cells, endothelial cells, and submucosal gland of normal nasal mucosa, but only in the endothelial cells in nasal polyp. CA II in normal mucosa was intensely expressed in the submucosal gland cells and CA IX was noted in the cytoplasm and plasma membrane of epithelial cells and submucosal glands. However, these findings were not found in nasal polyp. Western blot also showed differences in their expression levels.
These results indicate that CA may participate in the physiology of normal nasal mucosa, but also suggest that altered their expression in nasal polyps may cause impaired electrolyte and water transport across the epithelial cells.
The Laryngoscope 08/2008; 118(10):1856-61. · 1.75 Impact Factor
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ABSTRACT: The distribution and properties of branched chain amino acid aminotransferase(EC 2.6.1.42) was investigated in adult Fasciola hepatica. Fasciola hepatica was fractionated by differential centrifugation into nuclear, mitochondrial and cytosolic fractions. The activity of branched chain amino acid aminotransferase was measured by the method of Ichihara and Koyama (1966). Isozyme patterns of this enzyme was also examined by DEAE-cellulose column chromatography. The results obtained were as follows: 1. The activity in homogenate was found to be 12.69 units/g wet tissue. The activity of this enzyme was relatively high compared with those in rat tissues. 2. The distribution of branched chain amino acid aminotransferase in the subcellular organelles showed that 87.8 % of the activity was in cytosolic, 10.9 % in mitochondrial and 1.3 % was in nuclear fraction. 3. Cytosolic fraction of Fasciola hepatica contained Enzyme I, but not Enzyme II and III, of branched chain amino acid aminotransferase. Enzyme I was eluted by 50 mM phosphate buffer from DEAE-cellulose column and catalyzed the transamination of all three branched chain amino acids. 4. The Enzyme I was purified about 22-folds increase in specific activity after chromatography on DEAE-cellulose. 5. The best substrate among three amino acids (leucine, isoleucine and valine) was L-isoleucine. 6. The optimal temperature of Enzyme I was 45 degrees C and the optimal pH was 8.2. 7. The Km value for leucine of Enzyme I was 4.17 mM. 8. The Km values for alpha-ketoglutarate and pyridoxal phosphate of Enzyme I were 0.41 mM and 4.76 x 10(-3) mM, respectively.
Kisaengch'unghak chapchi. The Korean journal of parasitology. 07/1983; 21(1):49-57.
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ABSTRACT: The intestinal lesions were studied in dog metagonimiasis by reinfection. The metacercariae of M. yokogawai were collected from naturally infected sweetfish. A total of twenty dogs were divided into three groups; control, primary infection and reinfection groups. The 18 dogs were infected with 10,000 metacercariae; the 5 dogs in primary infection group were killed at the 5 days in 1 week, 4 weeks, 6 weeks after the infection. The remaining 13 dogs were kept for nine weeks, and challenged again with 5,000 metacercaricae. The reinfected dogs were killed at the 1 day, 3 days, 5 days and 1 week, 2 weeks, 4 weeks, 6 weeks, 8 weeks respectively. The chronologic changes of the intestinal lesions in both groups, the worm recovery rate, and distribution patten were examined by gross observation, light and scanning electron microscopies. The results were summarized as follows: 1. Worm recovery rate in primary infection group ranged from 19.8% to 37.8%. The rates were 6.3% to 16.3% in reinfected dogs within 5 dats. And the ratio of young worms collected to old ones was 1:1.83. In primary infection group, the collected worms were distributed in upper portion of the small intestine, while the distribution of worms shifted down to the lower portion of the small intestine in reinfection group. 2. In primary infection group, gross pathologic findings of intestinal mucosa began to appear in the 5th day and the 1st week after infection. The changes were effacement of transverse folds, watery or serous intestinal content, and enlargement of Peyer's patches as well as mesenteric lymph nodes. After the 4 week of infection, these findings returned to normal. In the reinfection group, these findings did occur again, but were lighter in degree when compared with primary infection group in early phase of infection. Again the gross changes returned to normal in two weeks which resolved earlier than in promary infection groups. 3, By histopathologic observations, mucosal changes such as blunted, adhered villi with hyperplasia of crypt epithelium, stromal changes, edema, and inflammatory cell infiltration were observed. These regressed mucosal changes were returned to almost normal, except for inflammatory cell infiltration. The reinfected dogs showed less severe lesions of the small intestine, with shorter period of the changes especially in aspect of villous changes. 4. By the scanning electron microscopy, the histopathological findings of villi lesions were also confirmed. From the above results, it was inferred that the so-called spontaneous and/or self cure phenomena were of negligible importance in metagonimiasis in dogs. In the chronologic observations of pathologic process in intestine, it was also suggested that the host immunity tend to recover the intestinal integrity. And early invasion of young worms to the Lieberkuhn's crypt was considered as the primary cause of lesions of villi.
Kisaengch'unghak chapchi. The Korean journal of parasitology. 07/1983; 21(1):58-73.
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ABSTRACT: Ten adult worms of Pharynogostomum cordatum were recovered from a cat instesine purchased in August 1980 at the Namdaemun Market, Seoul, Korea. It is the first case report of cat pharyngostomiasis in Korea.
Kisaengch'unghak chapchi. The Korean journal of parasitology. 01/1982; 19(2):173-174.
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ABSTRACT: To study the basic pathological changes of small intestine in metagonimiasis, light- and electron microscopic studies were made, using a total of 21 cats which were experimentally infected with metacercariae of Metagonimus yokogawai. The metacercariae were obtained from naturally infected sweetfish (Plecoglossus altivelis) by digestion technique. The cats were divided in control, light-infection(10,000 metacercariae infected) and heavy-infection(50,000 metacercariae infected) groups. Cats were killed at the 5th, 10th, 15th day, and 4th, 8th and 10th week after the infection. And the small intestine was prepared for the study. Pathological studies comprised gross examination, worm distribution pattern, light microscopic examination and both transmission and scanning electron microscopic examinations. The results obtained were summarized as follows. 1. Gross morphologic changes were the most marked during the first 2 weeks after infection. The gross abnormalities were severer in the heavily infected animals. The changes were dryness and listlessness of serosal surface due to dehydration, mushy and/or watery intestinal content, effacement of transverse nodes and enlargement of mesenteric lymph folds and Peyer's patches. After 4 weeks of infection, these changes became less marked showing a tendency to return to normal. 2. The sectioned flukes were distributed from duodenum to proximal ileum. However, individual variation was marked in distribution. In the heavy-infection group, the locality of parasitism tended to extend more distally. 3. The locality of M. yokogawai in the intervillous space was mostly in the lower-most portion of intervillous space, where they compressed and eroded epithelial cells probably due to mechanical damage to the structure. Very rarely the worms were found in lumen of Lierberkuehn's crypt, and reaching, in two occasions, into proprial lymphoid tissue. 4. Light-microscopically the lesion was restricted in mucosa: Early mucosal changes were shortening, blunting, fusion, and thickening of the villi, crypt hypertrophy with consequent decrease of villus/crypt ratio, as well as stromal changes of edema, capilliary ectasia and marked inflammatory cell infiltration of lymphocytes and plasma cells. Goblet cells were markedly reduced in number as with depletion of its cytoplasmic content. In the later stages of infection, mucosa restored its normal configuration in spite of persistent parasitism of the worms. 5. At the infection stage of 5-15 days, there was significant shortening of the microvillous height with varible destruction of glycocalyx in electron microscopic examination. With lapse of infection time, microvilli became to restore the normal pattern. With these morphological changes, it appears that diarrhea in experimental metagonimiasis would be related to the decrease of absorptive surface of the small intestine particularly in the early phase of infection. The significant changes seen in villi and microvilli might be due to massive intrusion or invasion of Metagonimus worms into the crypts, causing direct mechanical and possible host-immune response to the small bowel mucosa.
Kisaengch'unghak chapchi. The Korean journal of parasitology. 01/1982; 19(2):109-129.
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ABSTRACT: Santonin-kainic acid complex was evaluated as a chemotherapeutic of the mass treatment of the Ascaris lumbricoides infection in Korea. The results could be summarized as follows: 1) The negative conversion rate was 82.9% in average in 4 treated groups. Some variations of negative conversion rate among the treated groups were noticed. 2) The egg reduciton rate was 97.7% in average and the results were rather uniform among the three evaluated groups. 3) By the analysis of egg reduction, it seems that the lightly infected cases whose E.P.G. were under 5,000 were resistant to treatment with the less reduced egg output. 4) After the treatment with this complex, the number of egg discharged cases were reduced to 1.84% and the average number of discharge eggs per incompletely treated or untreated cases were reduced to 12.5% compared with the level of before-treatment egg output. 5) The successive observations of the pattern of worm expulsion after drug intake was made. The worms were mostly expelled in the stool within 3 days, and 58.9% of total expelled worms were collected within 24-hour stool. 6) The minimum length of the immature worms expelled was 7.6cm. Among the 659 Ascaris collected in the first-day stool from 91 rural people, 8.5% were in the range of 7.6-12.2 cm-long, immature worms. The sex ratio, male: female= 0.69: 1.
Kisaengch'unghak chapchi. The Korean journal of parasitology. 09/1972; 10(2):79-85.
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ABSTRACT: The authors examined 3,169 fecal specimens from inhabitants of seven localities such as City, Eups and Myons in Cheju Do on July 1970 with cellophane thick smear technique. The results were analysed and summarized as follows: 1) The overall egg positive rate of helminths was 82.2% and it was attributed to high rates of soil-transmitted helminths as in case of other parts in Korea. 2) The infection rates of each species were; A. lumbricoides 44.3%, T. trichiurus 65.6%, hookworm 1.5%, T. orientalis 0.8%, C. sinensis 0.2%, P. westermani 0.4%, M. yokogawai 0.9%, Taenia sp. 12.7% and H. nana 1.4%. 3) The infection rates of soil-transmitted helminths were relatively lower than those of mainland Korea especially in case of hookworm and T. orientalis. The proportion of unfertilized ova passers among the Ascaris infected case was 22.1%. 4) The ova of heterophyids, most probably Metagonimus yokogawai were detected in lower percentage but discovered throughout the localities surveyed and in all age groups. It is certainly presumed that Metagonimus infection is autochthonous. 5) The most interesting results were obtained in Taenia sp. infection and the higher rates were shown in rural area than in urbanized areas. The positive rates were within 5% in childhood and adolescence but abruptly increased up to 36.4 % in adults.
Kisaengch'unghak chapchi. The Korean journal of parasitology. 09/1972; 10(2):100-108.
