• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1699-1702
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• 2014

Objective: To evaluate clinical efficacy of a dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung (NSCLC). Methods: Patients with locally advanced NSCLC were treated with conventional fractionated radiotherapy or three dimensional conformal radiotherapy (3 DCRT), concurrently with a dose escalating schedule of paclitaxel. All patients were divided into three groups, A with paclitaxel $30mg/m^2$, B with paclitaxel $60mg/m^2$ and C with paclitaxel $90mg/m^2$. Paclitaxel was repeated every week for a total of 4 or 6 weeks. Results: Among 109 patients, response rates were 68.8%, 71.1% and 71.8% (p>0.05) for group A (n=32), B (n=38), and C (n=39) respectively. Accordingly, disease control rates were 81.3%, 81.6% and 82.1% (p>0.05). Progression-free survival time was $8.0{\pm}5.0$ months, $11.6{\pm}6.1$ months, and $14.8{\pm}7.9$ months (p<0.05), respectively. Overall survival time was $15.4{\pm}7.6$ months, $18.2{\pm}8.0$ months, and $22.0{\pm}7.6$ months (p<0.05), one-year survival rates were 62.5%, 73.1% and 90.0% (p>0.05) and two-year survival rates were 31.3%, 38.5% and 50.0% (p<0.05). Main side-effects were bone marrow suppression, radiation related esophagitis and gastrointestinal reaction. Conclusion: In treating patients with NSCLC, concurrent chemoradiotherapy with paclitaxel improves early response compared with conventional fractionated radiotherapy or 3 DCRT. The survival rate was improved with the addition of paclitaxel, but there was an increase in adverse reactions when the dose of paclitaxel was increased.

• Korean Journal of Community Nutrition
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• v.3 no.1
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• pp.76-93
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• 1998

Three hundred sixty-two(male 131, female 231) elderly aged over 65 in Chungb- uk area were interviewed to determine the disease states and drug usage patterns. The prebalence of disease was 78% and women reported more chronic diseases(83%) than men(71%). Elderly who live with spouse and have an occupation have a lower rate of disease. Average number of diseases of the elderly was $1.8\pm{1.1}$, and women$(2.1\pm{1.3)}$ have significantly higher average number of diseases than that of men$(1.4\pm{0.7)}$. Also the elderly in urban areas$(2.1\pm{1.4)}$ have significantly higher number of diseases than that of the elderly in rural areas$(1.6\pm{0.9)}$. Arthritis, hypertension, cardiovascular and gastric diseases were the most frequently listed chronic diseases in order for both men and women. Anemia and fracture of bone were relatively higher in women than in men. Particularly, the arthritis of the urban elderly have a rate of 1.5 times higher than that of the rural elderly. Fifty-two percent of the elderly were currently using drugs ; among drug users 71.2% used prescription drugs and 20.5% used nonprescription drugs. The average number taken per person was 2.1$\pm$1.4 and there was no sex or age difference. However, the elderly in rural areas $(2.7\pm{1.7)}$ consumed a significantly higher number of drugs than those in urban areas$(1.7\pm{0.7)}$. The average number of prescripti- on drugs taken was 2.0$\pm$1.4 while the average of nonprescription drugs taken was $(1.3\pm{0.6)}$. Analgesics and antihypertensive drugs were most commonly used. Vitamin and analgesics were the most frequently used self-prescribed drugs. It was noted that potential adverse drug interaction by concominant drug consumption for arthritis and antihypensive drug, abuse of digestants and antiacid without treatment of the underlying disease, and misuse of quick-acting bowel medications were problematic for the elderly. In addition drugs used for the elderly have some adverse effect on the digestive system. The types and composition of drugs used by the elderly were identified and presented. Medication compliance was poor and 13.5% reported adverse reactions such as edema, heartburn, nausea, and difficulty with eating. Seventeen percent of the elderly obtained drugs arranged by those other than medical staff. Also, even among those elderly who obtained drugs prescribed by a doctor, 69.1% of subjects had not receive instruction about potential adverse reactions. These results suggest that nutritional problems related to drug usage might exist and so dietitians, either individually or as members of health teams, need to have a better understanding of drug-nutrient interaction and closer supervision, and drug information/education service should therefore be provided to prevent or minimize adverse drug reaction in elderly users of medication.

• Korean Journal of Veterinary Research
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• v.39 no.2
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• pp.247-256
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• 1999

A disease of young Holstein calves characterized by recurrent pneumonia, ulcerative and granulomatous stomatitis, enteritis with bacterial overgrowth, periodontitis, delayed wound healing, persistent neutrophilia and death at an early age had been originally described in 1983 and again in 1987. Most of these calves had stunted growth and a persistent, progressive neutrophilia (often exceeding 100,000/ml). By investigation of pedigrees, all of the affected calves have now been traced to a common sire and confirmed by polymerase chain reaction (PCR) diagnostic DNA testing to be homozygous carriers of a defective allele for bovine CD18. Neutrophils from these calves have several functional deficits and, most importantly, fail to adhere in a ${\beta}_2$-integrin dependent manner. The ${\beta}_2$-integrins represent a family of glycoproteins which participate in various leukocyte adhesion reactions during host defense. The presence or absence of ${\beta}_2$-integrin molecules can be demonstrated on the surface of neutrophils, monocytes and lymphocytes from normal or affected calves using specific monoclonal antibodies and flow cytometry, or by colloidal gold immunolabeling and scanning electron microscopy in backscatter mode. Deficiency of the ${\beta}_2$-integrins on all leukocyte types in Holstein calves is analogous to leukocyte adhesion deficiency (LAD) seen in humans. Neutrophils in bovine (BLAD) and human LAD patients are unable to adhere to the endothelial lining of the cardiovascular system thus interrupting egression of neutrophils into infected tissues. Other leukocytes, while still deficient in expression of the ${\beta}_2$-integrins, are still able to efficiently egress from the blood stream due to interactions of other adhesion molecules that are not as highly expressed on neutrophils. Both BLAD cattle and LAD children (who do not receive bone marrow transplants) often die at an early age as a result of the failure of neutrophils to extravasate into infected tissues. In 1991, Shuster, et $al^{27}$, identified two point mutations within the alleles encoding bovine CD18 in a Holstein calf afflicted with leukocyte adhesion deficiency. One mutation causes an aspartic acid to glycine substitution at amino acid 128 (D128G) in an extracellular region of this adhesion glycoprotein that is highly conserved (> 95% identity) between humans, cattle and mice. The other mutation is silent. Numerous calves with clinical symptoms of leukocyte adhesion deficiency have since been tested and all have been found homozygous for the D128G allele. In addition, calves homozygous far the D128G allele have been identified during widespread DNA testing in the United States. All cattle with the mutant allele are related to one bull, who through artificial insemination (A.I.), sired many calves in the 1950's and 1960's. The carrier frequency of the D128G CD18 allele among U.S. Holstein cattle had reached approximately 15% among active A.I. bulls and 8% among cows. By 1993, the organization of the dairy industry and the diagnostic test developed to genotype cattle, enabled virtually complete eradication of bovine leukocyte adhesion deficiency among current and future A.I. bulls.

• IMMUNE NETWORK
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• v.11 no.1
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• pp.79-94
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• 2011

Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.

• Journal of Periodontal and Implant Science
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• v.36 no.1
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• pp.39-49
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• 2006

1. 목 적 이 연구의 목적은 성견의 하악 골 결손부에 이식한 생체 유래 골 이식재에 대한 치조골의 반응을 알아보는 것이다. 2. 연구방법 및 재료 생후 1년 이상 된 성견 4마리의 하악 제2소구치 및 제 4 소구치를 발거하고 발치와에 금원심 폭경 8mm, 협설 폭경 5mm, 치조정에서의 깊이 6mm인 결손부를 형성하였다. 4주간의 자연 치유 후 판막을 형성하여 결손부의 크기를 확인하였다. 각각의 결손부 크기가 일정하도록 수정한 후 '이식재+차폐막'군에는 OCS-B을 이식하고 Bio-gide을 차단막으로 사용한 후 봉합하고 '이식재군'은 OCS-B 이식 후 차폐막 없이 봉합하였으며 '비이식'군은 아무런 처치없이 일차봉합하였다. 수술 4, 6주에 실험동물을 각각 희생시켜 실험부위를 적출하고 비탈회 연마 표본을 제작하여 골 치유 양성을 조직학적 및 조직계측학적으로 관찰하였다. 3. 연구결과 이식재 비이식군 및 이식군 모돼서 별다른 부작용없이 잘 치유되었다. 세 실험군 모두에서 술후 4주에 비교하여 술 후 6주에서의 결손부 산생골 형성량이 증가하였다. 술후 4주 소견에서 비이식군은 결손부 주변부위에서 골이 생성되어 나오는 양상을 보였으며 이식군은 이식재 주변으로 골침착 시작되는 것을 관찰할 수 있었다. 술후 6주 소견에서 비이식군은 결손부 경계부로부터의 지속적인 골 생성을 관찰할 수 있었으며 이식군은 이식재 주변으로 침착된 골의 양이 많아지고 신생골이 가교를 형성하는 것을 관찰할 수 있었다. 4. 결 론 차폐막 유무와 상관없이 OCS-B는 염증반응을 전혀 일으키지 않았으며 우수한 골 전도성을 보였다. 또한 결손부의 형태를 잘 유지하여 골재생을 위한 공간을 확보할 수 있었다. 이는 OCS-B가 골이식재로서의 필요조건을 갖추었음을 확인한 결과이며 보다 장기적인 관찰에서 OCS-B의 흡수 가능성을 확인하는 것이 필요할 것으로 보인다.

• Journal of Periodontal and Implant Science
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• v.37 no.4
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• pp.655-669
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• 2007

Reactive oxygen species (ROS) have been implicated in the pathogenesis of various diseases. And vitamin C has shown a protective effect for the tissues. The aim of this study was to evaluate the effects of $H_2O_2$ and ascorbic acid on matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase (TIMP: TIMP-1, TIMP-2), Type 1 collagen, fibronectin, and PDLs22 level in human periodontal ligament fibroblasts (hPDLF) via reverse transcription-polymerase chain reaction (RT-PCR). hPDLF was obtained from a healthy periodontium and cultured in Dulbecco's modified Eagles's medium plus 10% fetal bone serum. The concentration of ascorbic acid in hPDLF was $50{\mu}g/ml$, and that of $H_2O_2$ in hPDLF was 0.03% and 0.00003%. Ascorbic acid only, $H_2O_2$ only and mixture of ascorbic acid and $H_2O_2$ were applied with hPDLF for 1-, 3-, and 30-min. respectively. The gene expression of MMP-1-, TIMP-1-, TIMP-2-, Type 1 collagen-, fibronectin-, and PDLs22-mRNA in hPDLF was analysed via RT-PCR. The results were as follows; 1. hPDLF in response to 30-min. incubation with 0.03% $H_2O_2$ did not show any gene expression. 2. In all the experimental groups, the gene expression of fibronectin mRNA showed the decreased tendency compared to control. 3. In all the experimental groups, the gene expression of TIMP-1 mRNA showed the tendency similar to control. 4. hPDLF in response to 30-min. incubation with 0.03% $H_2O_2$ and ascorbic acid increased mRNA induction for MMP-1. 5. In all the experimental groups, hPDLF increased mRNA induction for PDLs22, collagen type 1, and TIMP-2 compared to control. Within the limited experiments, $H_2O_2$ and ascorbic acid increased mRNA induction for PDLs22, collagen type 1, TIMP-2 in hPDLF. More research will be needed in order to confirm the relative importance of the different roles of ROS and antioxidants in hPDLF from a periodontal regeneration or repair standpoint.

• The Journal of the Korean bone and joint tumor society
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• v.12 no.2
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• pp.103-111
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• 2006

Purpose: Sternocostoclavicular hyperostosis (SCCH) is a disease of unknown etiology, which is characterized by periosteal reaction and endosteal hyperossification of the sternum, clavicles and upper ribs as well as ossification of the surrounding soft tissue. SCCH is a well recognized but uncommon condition which is important differential diagnosis to consider to avoid misdiagnosis and to differentiate the condition from malignant process. But few studies have reported long-term clinical result of SCCH. We report long-term clinical result of SCCH. Materials and Methods: From 1986 to 2000, 17 cases of SCCH were followed up over two to 14 years. We evaluated the radiologic, pathologic and clinical results. Results: Four men and thirteen women were studied. The age when first symptom appeared were raged from17 to 60(average-48.7) There are no specific bacteriological, serological or histological finding. Usually a permanent increase in the erythrocyte sedimentation rate is found. The radiological examination showed the signs of proliferate destructive arthritis in most case. The majority of patients respond to NSAIDs and antibiotics. Conclusion: Sternocostoclavicular hyperostosis is uncommon benign condition, but important condition in the differential diagnosis of inflammatory or malignant process of this joint.

• Korean Journal of Materials Research
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• v.21 no.7
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• pp.384-390
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• 2011

Ti-6Al-4V ELI (Extra Low Interstitial) alloy has been widely used as an alternative to bone due to its excellent biocompatibility. However, it still has many problems, including a high elastic modulus and toxicity. Therefore, nontoxic biomaterials with a low elastic modulus should be developed. However, the fabrication of a uniform coating is challenging. Moreover, the coating layer on Ti and Ti alloy substrates can be peeled off after implantation. To overcome these problems, it is necessary to produce bulk Ti and Ti alloy with hydroxyapatite (HA) composites. In this study, Ti, Nb, and Zr powders, which are biocompatible elements, were milled in a mixing machine (24h) and by planetary mechanical ball milling (1h, 4h, and 6h), respectively. Ti-35%Nb-7%Zr and Ti-35%Nb-7%Zr-10%HA composites were fabricated by spark plasma sintering (SPS) at $1000^{\circ}C$ under 70MPa using mixed and milled powders. The effects of HA addition and milling time on the biocompatibility and physical and mechanical properties of the Ti-35%Nb-7%Zr-(10%HA) alloys have been investigated. $Ti_2O$, CaO, $CaTiO_3$, and $Ti_xP_y$ phases were formed by chemical reaction during sintering. Vickers hardness of the sintered composites increases with increased milling time and by the addition of HA. The biocompatibilty of the HA added Ti-Nb-Zr alloys was improved, but the sintering ability was decreased.

• Molecules and Cells
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• v.40 no.2
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• pp.133-142
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• 2017

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

• Toxicological Research
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• v.35 no.1
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• pp.45-63
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• 2019

In view of the growing industrial use of Bacterial cellulose (BC), and taking into account that it might become airborne and be inhaled after industrial processing, assessing its potential pulmonary toxic effects assumes high relevance. In this work, the murine model was used to assess the effects of exposure to respirable BC nanofibrils (nBC), obtained by disintegration of BC produced by Komagataeibacter hansenii. Murine bone marrow-derived macrophages ($BMM{\Phi}$) were treated with different doses of nBC (0.02 and 0.2 mg/mL, respectively 1 and $10{\mu}g$ of fibrils) in absence or presence of 0.2% Carboxymethyl Cellulose (nBCMC). Furthermore, mice were instilled intratracheally with nBC or nBCMC at different concentrations and at different time-points and analyzed up to 6 months after treatments. Microcrystaline $Avicel-plus^{(R)}$ CM 2159, a plant-derived cellulose, was used for comparison. Markers of cellular damage (lactate dehydrogenase release and total protein) and oxidative stress (hydrogen peroxidase, reduced glutathione, lipid peroxidation and glutathione peroxidase activity) as well presence of inflammatory cells were evaluated in brochoalveolar lavage (BAL) fluids. Histological analysis of lungs, heart and liver tissues was also performed. BAL analysis showed that exposure to nBCMC or CMC did not induce major alterations in the assessed markers of cell damage, oxidative stress or inflammatory cell numbers in BAL fluid over time, even following cumulative treatments. $Avicel-plus^{(R)}$ CM 2159 significantly increased LDH release, detected 3 months after 4 weekly administrations. However, histological results revealed a chronic inflammatory response and tissue alterations, being hypertrophy of pulmonary arteries (observed 3 months after nBCMC treatment) of particular concern. These histological alterations remained after 6 months in animals treated with nBC, possibly due to foreign body reaction and the organism's inability to remove the fibers. Overall, despite being a safe and biocompatible biomaterial, BC-derived nanofibrils inhalation may lead to lung pathology and pose significant health risks.