• Journal of Genetic Medicine
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• v.4 no.1
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• pp.22-37
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• 2007

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases, clinically and genetically heterogeneous, characterized by degeneration of spinocerebellar pathways with variable involvement of other neural systems. At present, 27 distinct genetic forms of SCAs are known: SCA1-8, SCA10-21, SCA23, SCA25-28, DRPLA (dentatorubral-pallidoluysian atrophy), and 16q-liked ADCA (autosomal dominant cerebellar ataxia). Epidemiological data about the prevalence of SCAs are restricted to a few studies of isolated geographical regions, and most do not reflect the real occurrence of the disease. In general a prevalence of about 0.3-2 cases per 100,000 people is assumed. As SCA are highly heterogeneous, the prevalence of specific subtypes varies between different ethnic and continental populations. Most recent data suggest that SCA3 is the commonest subtype worldwide; SCA1, SCA2, SCA6, SCA7, and SCA8 have a prevalence of over 2%, and the remaining SCAs are thought to be rare (prevalence <1%). In this review, we highlight and discuss the SCA7. The hallmark of SCA7 is the association of hereditary ataxia and visual loss caused by pigmentary macular degeneration. Visual failure is progressive, bilateral and symmetrical, and leads irreversibly to blindness. This association represents a distinct disease entity classified as autosomal dominant cerebellar ataxia (ADCA) type II by Harding. The disease affectsprimarily the cerebellum and the retina by the moderate to severe neuronal loss and gliosis, but also many other central nervous system structures as the disease progresses. SCA7 is caused by expansion of an unstable trinucleotide CAG repeat in the ATXN7 gene encoding a polyglutamine (polyQ) tract in the corresponding protein, ataxin-7. Normal ATXN7 alleles contain 4-35 CAG repeats, whereas pathological alleles contain from 36->450 CAG repeats. Immunoblott analysis demonstrated that ataxin-7 is widely expressed but that expression levels vary among tissues. Instability of expanded repeats is more pronounced in SCA7 than in other SCA subtypes and can cause substantial lowering of age at onset in successive generations termed ‘anticipation’ so that children may become diseased even before their parents develop symptoms. The strong anticipation in SCA7 and the rarity of contractions should have led to its extinction within a few generations. There is no specific drug therapy for this neurodegenerative disorder. Currently, therapy remains purely symptomatic. Cellular models and SCA7 transgenic mice have been generated which constitute valuable resources for studying the disease mechanism. Understanding the pathogenetic mechanisms of neurodegeneration in SCAs should lead to the identification of potential therapeutic targets and ultimately facilitate drug discovery. Here we summarize the clinical, pathological, and genetic aspects of SCA7, and review the current understanding of the pathogenesis of this disorder. Further, we also review the potential therapeutic strategies that are currently being explored in polyglutamine diseases.

• Journal of the Korean GEO-environmental Society
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• v.24 no.9
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• pp.33-40
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• 2023

The lateral load which is applied to the pile foundation supporting the superstructure during an earthquake is divided into the inertia force of the upper structure and the kinematic force of the ground. The inertia force and the kinematic force could cause failure to the pile foundation through different complex mechanisms. So it is necessary to predict and evaluate interaction of the ground-pile-structure properly for the seismic design of the foundation. The interaction is affected by the lateral behavior of the structure, the length of the pile, the boundary conditions of the head, and the relative density of the ground. Confining pressure and ground stiffness change accordingly when the relative density changes, and it results that the coefficient of subgrade reaction varies depending on each system. Horizontal bearing behavior and capacity of the pile foundation vary depending on lateral load condition and relative density of the sandy soil. Therefore, the 1g shaking table tests were conducted to confirm the effect of the relative density of the dried sandy soil to dynamic behavior of the group pile supporting the superstructure. The result shows that, as the relative density increases, maximum acceleration of the superstructure and the pile cap increases and decreases respectively, and the slope of the p-y curve of the pile decreases.

• KSCE Journal of Civil and Environmental Engineering Research
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• v.26 no.6C
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• pp.407-419
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• 2006

Situations where support is provided solely in shaft resistance of drilled shafts are where the base of the drilled hole cannot be cleaned so that it is uncertain that any end bearing support will be developed. Alternatively, where sound bed rock underlies low strength overburden material, it may be possible to achieve the required support in end bearing on the rock only, and assume that no support is developed in the overburden. However, where the drilled shaft is drilled some depth into sound rock, a combination of side wall resistance and end bearing can be assumed. Both theoretical and field studies of the performance of rock socketed drilled shafts show that the major portion of applied load is usually carried in side wall resistance. Normal stress at the rock-concrete interface is induced by two mechanisms. First, application of a compressive load on the top of the pile results in elastic dilation of the concrete, and second, shear displacement at the rough surface of the drilled hole results in mechanical dilation of the interface. If the stiffness of the material surrounding the socket with respect to normal displacement is constant, then the normal stress will increase with increasing applied load, and there will be a corresponding increase in the shear strength. In this study, the numerical analyses are carried out to investigate the behavioral characteristics of side of rock socketed drilled shafts. The cause of non-linear head load-settlement relationship and failure mechanism at side are also investigated properly and the design charts are suggested and verified for the leading to greater efficiency and reliability in the pile design.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.45.1-45.22
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• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.180-189
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• 2004

Although the outcome of cancer patients after cytotoxic chemotherapy is related diverse mechanisms, multidrug resistance (MDR) for chemotherapeutic drugs due to cellular P-glycoprotein (Pgp) or multidrug-resistance associated protein (MRP) is most important factor in the chemotherapy failure to cancer. A large number of pharmacologic compounds, including verapamil, quinidine, tamoxifen, cyclosporin A and quinolone derivatives have been reported to overcome MDR. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transporter. $^{99m}Tc$-MIBI and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of PgP-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and $N-[^{11}C]acetyl-leukotriene$ E4 provides an opportunity to study MRP function non-invasively in vivo. SPECT and PET pharmaceuticals have successfully used to evaluate pharmacologic effects of MDR modulators. Imaging of MDR and reversal of MDR with bioluminescence in a living animal is also evaluated for future clinical trial. We have described recent advances in molecular imaging of MDR and reviewed recent publications regarding feasibility of SPECT and PET imaging to study the functionality of MDR transporters in vivo.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.222-230
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• 1994

Background: Paraquat, a widely used herbicide, is extremely toxic, causing multiple organ failure in humans. Paraquat especially leads to irreversible progressive pulmonary fibrosis, which is related to oxygen free radicals. However, its biochemical mechanism is not clear. Natural mechanisms that prevent damage from oxygen free radicals include changes in glutathione level, G6PDH, superoxide dismutase(SOD), catalase, and glutathione peroxidase. The authors think catalase is closely related to paraquat toxicity in the lungs Method: The effects of 3-amino-1,2,4-triazole(aminotriazole), a catalase inhibitor, on mice administered with paraquat were investigated. We studied the effects of aminotriazole on the survival of mice administered with paraquat, by comparing life spans between the group to which paraquat had been administered and the group to which a combination of paraquat and aminotriazole had been administered. We measured glutathion level, glucose 6-phosphate dehydrogenase(G6PDH), superoxide dismutase(SOD), catalase, and glutathione peroxidase(GPx) in the lung tissue of 4 groups of mice: the control group, group A(aminotriazole injected), group B(paraquat administered), group C(paraquat and aminotriazole administered). Results: The mortality of mice administered with paraquat which were treated with aminotriazole was significantly increased compared with those of mice not treated with aminotriazole. Glutathione level in group B was decreased by 20%, a significant decrease compared with the control group. However, this level was not changed by the administration of aminotriazole(group C). The activity of G6PDH in all groups was not significantly changed compared with the control group. The activities of SOD, catalase, and glutathione peroxidase(GPx) in the lung tissue were significantly decreased by paraquat administration(group B); catalase showed the largest decrease. Catalase and GPX were significantly decreased by aminotriazole treatment in mice administered with paraquat but change in SOD activity was not significant(group C). Conclusion: Decrease in catalase activity by paraquat suggests that paraquat toxicity in the lungs is closely related to catalase activity. Paraquat toxicity in mice is enhanced by aminotriazole administration, and its result is related to the decrease of catalase activity rather than glutathione level in the lungs. Production of hydroxyl radicals, the most reactive oxygen metabolite, is accelerated due to increased hydrogen peroxide by catalase inhibition and the lung damage probably results from nonspecific tissue injury of hydroxyl radicals.

• Journal of Chest Surgery
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• v.42 no.6
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• pp.685-695
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• 2009

Background: Calcification is the most frequent cause of clinical failure of bioprosthetic tissues that are fabricated from Glutaraldehyde (GA)-fixed porcine valve or bovine pericardium. We recently used a multi-factorial approach of employing different mechanisms to investigate how to reduce the calcification of bioprosthetic tissues. The purpose of the present study was to evaluate the synchronized synergism using ethanol, L-lysine and $NaBH_4$ in glutaraldehyde treated porcine pericardium from the standpoint of calcification and tissue elasticity. Material and Method: Porcine pericardium was fixed with 0.625% GA (commercial fixation). An interim step of ethanol (80%; 1 day at room temperature) or L-lysine (0.1 M; 2 days at $37^{\circ}C$) or $NaBH_4$ (0.1 M; 2 days at room temperature) was followed by completion of the GA fixation (2 days at $4^{\circ}C$ and 7 days at room temperature). The tensile strength and thickness of the samples were measured. The treated pericardiums were implanted subcutaneously into three-week old Sprague-Dawley rats for 8 weeks. The calcium content was assessed by atomic absorption spectroscopy and the histology of the samples. Result: The amount of calcium in the pericardium pretreated with ethanol (13.6${\pm}$10.0 ug/mg, p=0.008), L-lysine (15.3${\pm}$1.0 ug/mg, p=0.002) and both (16.1${\pm}$11.1 ug/mg, p=0.012) was significantly reduced compared with the control (51.2${\pm}$8.5 ug/mg). However, $NaBH_4$ pretreatment (65.7${\pm}$61.8 ug/mg, p=0.653) and combined pretreatment that including ethanol, L-lysine and $NaBH_4$ (92.9${\pm}$58.3 ug/mg, p=0.288) were not significantly different from the controls(51.2${\pm}$8.5 ug/mg). Both the combined pretreatment using ethanol and L-lysine (7.60${\pm}$1.55, p=0.76) and the combined pretreatment that included ethanol, L-lysine and $NaBH_4$ (7.47${\pm}$1.85, p=0.33) increased the tensile strength/thickness ratio compared with that of the controls (4.75${\pm}$1.88). Conclusion: The combined pretreatment using ethanol and L-lysine seemed to decrease the calcification of porcine pericardium fixed with glutaraldehyde, as compared to single pretreatment, and it increase the tissue elasticity, but to the degree that showed synchronized synergism. $NaBH_4$ pretreatment seemed to increase the calcification of porcine pericardium, irrespective of whether single or combined pretreatment was used.

• (The)Study of the Eastern Classic
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• no.37
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• pp.473-507
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• 2009

The purpose of this study is to understand Zhuxi's Taoxuezhengzhi(道學政治) by reorganizing both his political opinion in each different political situation and his consistent political consciousness appeared in his whole political career. He concluded that the politics was the real problematic in Southern Sung, which made its structure distorted. This distorted structure of politics had widely rooted in whole sphere of society. In order to cure this political problematic, Zhuxi had focused on huangdi(皇帝) and chaoting(朝廷). That is why people is the basis of State and the result of politics, while huangdi and chaoting is the basis of politics and the beginnig of politics. According to Zhuxi, forming their political power group of their own will by using huangdi's power, the political elites close to only to huangdi made the function of chaoting unstable, with the result that the political decay produced. In chaoting, it resulted in the weakness of huangdi's power, the collapse of official discipline(紀綱), and the absence of public opinion(公論) and public aggreement(公議). Beyond chaoting, it resulted in the absence of political trust and the degeneration of public morals(風俗). In the Southern Sung were not altered the political orientation and culture based on the political decay, but only political orientation and characteristics of political elite only altered. This proves Zhuxi's approach that all problems in Southern Sung could resolve by the political approach. Zhuxi had suggested political issues in office. The alternatives for those political issues had basis of the theme, the one that saving people(恤民) is the purpose of politics. However his political ideas and the execution of them had been occsionally collapsed by the complex political structue, the mechanisms of political power, and the sameness and privatization of political geography in Southern Sung. Qingyuandanghuo(慶元黨禍) was the final stage of his political frustration, with the result that it led to the failure of Zhuxi's taoxuezhengzhi and interrupted the tradition of taoxue(道學) for the time being.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.452-461
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• 1994

Background: Tumor necrosis factor(TNF)-$\alpha$ and Interleukin(lL)-$1{\beta}$ are thought to play a major role in the pathogenesis of the septic syndrome, which is frequently associated with adult respiratory distress syndrome(ARDS). In spite of many reports for the role of TNF-$\alpha$ in the pathogenesis of ARDS, including human studies, it has been reported that TNF-$\alpha$ is not sensitive and specific marker for impending ARDS. But there is a possibility that the results were affected by the diversity of pathogenetic mechanisms leading to the ARDS because of various underlying disorders of the study group in the previous reports. The purpose of the present study was to evaluate the roles of TNF-$\alpha$ and IL-$1{\beta}$ as a predictable marker for development of ARDS in the patients with septic syndrome, in which the pathogenesis is believed to be mainly cytokine-mediated. Methods: Thirty-six patients of the septic syndrome hospitalized in the intensive care units of the Asan Medical Center were studied. Sixteens suffered from ARDS, whereas the remaining 20 were at the risk of developing ARDS(acute hypoxemic respiratory failure, AHRF). In all patients venous blood samples were collected in heparin-coated tubes at the time of enrollment, at 24 and 72 h thereafter. TNF-$\alpha$ and IL-$1{\beta}$ was measured by an enzyme-linked immunosorbent assay (ELISA). All data are expressed as median with interquartile range. Results: 1) Plama TNF-$\alpha$ levels: Plasma TNF-$\beta$ levels were less than 10pg/mL, which is lowest detection value of the kit used in this study within the range of the $mean{\pm}2SD$, in all of the normal controls, 8 of 16 subjects of ARDS and in 8 in 20 subjects of AHRF. Plasma TNF-$\alpha$ levels from patients with ARDS were 10.26pg/mL(median; <10-16.99pg/mL, interquartile range) and not different from those of patients at AHRF(10.82, <10-20.38pg/mL). There was also no significant difference between pre-ARDS(<10, <10-15.32pg/mL) and ARDS(<10, <10-10.22pg/mL). TNF-$\alpha$ levels were significantly greater in the patients with shock than the patients without shock(12.53pg/mL vs. <10pg/mL) (p<0.01). There was no statistical significance between survivors(<10, <10-12.92pg/mL) and nonsurvivors(11.80, <10-20.8pg/mL) (P=0.28) in the plasma TNF-$\alpha$ levels. 2) Plasma IL-$1{\beta}$ levels: Plasma IL-$1{\beta}$ levels were less than 0.3ng/mL, which is the lowest detection value of the kit used in this study, in one of each patients group. There was no significant difference in IL-$1{\beta}$ levels of the ARDS(2.22, 1.37-8.01ng/mL) and of the AHRF(2.13, 0.83-5.29ng/mL). There was also no significant difference between pre-ARDS(2.53, <0.3-8.34ngfmL) and ARDS(5.35, 0.66-11.51ng/mL), and between patients with septic shock and patients without shock (2.51, 1.28-8.34 vs 1.46, 0.15-2.13ng/mL). Plasma IL-$1{\beta}$ levels were significantly different between survivors(1.37, 0.4-2.36ng/mL) and nonsurvivors(2.84, 1.46-8.34ng/mL). Conclusion: Plasma TNF-$\alpha$ and IL-$1{\beta}$ level are not a predictable marker for development of ARDS. But TNF-$\alpha$ is a marker for shock in septic syndrome. These result could not exclude a possibility of pathophysiologic roles of TNF-$\alpha$ and IL-$1{\beta}$ in acute lung injury because these cytokine could be locally produced and exert its effects within the lungs.

• Journal of Global Scholars of Marketing Science
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• v.19 no.4
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• pp.44-56
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• 2009

Impulse purchasing is defined as an immediate purchase with no pre-shopping intentions. Previous studies of impulse buying have focused primarily on factors linked to marketing mix variables, situational factors, and consumer demographics and traits. In previous studies, marketing mix variables such as product category, product type, and atmospheric factors including advertising, coupons, sales events, promotional stimuli at the point of sale, and media format have been used to evaluate product information. Some authors have also focused on situational factors surrounding the consumer. Factors such as the availability of credit card usage, time available, transportability of the products, and the presence and number of shopping companions were found to have a positive impact on impulse buying and/or impulse tendency. Research has also been conducted to evaluate the effects of individual characteristics such as the age, gender, and educational level of the consumer, as well as perceived crowding, stimulation, and the need for touch, on impulse purchasing. In summary, previous studies have found that all products can be purchased impulsively (Vohs and Faber, 2007), that situational factors affect and/or at least facilitate impulse purchasing behavior, and that various individual traits are closely linked to impulse buying. The recent introduction of new distribution channels such as home shopping channels, discount stores, and Internet stores that are open 24 hours a day increases the probability of impulse purchasing. However, previous literature has focused predominantly on situational and marketing variables and thus studies that consider critical consumer characteristics are still lacking. To fill this gap in the literature, the present study builds on this third tradition of research and focuses on individual trait variables, which have rarely been studied. More specifically, the current study investigates whether impulse buying tendency has a positive impact on impulse buying behavior, and evaluates how consumer characteristics such as the need for cognitive closure (NFCC), psychological wellbeing, and susceptibility to interpersonal influences affect the tendency of consumers towards impulse buying. The survey results reveal that while consumer affective impulsivity has a strong positive impact on impulse buying behavior, cognitive impulsivity has no impact on impulse buying behavior. Furthermore, affective impulse buying tendency is driven by sub-components of NFCC such as decisiveness and discomfort with ambiguity, psychological wellbeing constructs such as environmental control and purpose in life, and by normative and informational influences. In addition, cognitive impulse tendency is driven by sub-components of NFCC such as decisiveness, discomfort with ambiguity, and close-mindedness, and the psychological wellbeing constructs of environmental control, as well as normative and informational influences. The present study has significant theoretical implications. First, affective impulsivity has a strong impact on impulse purchase behavior. Previous studies based on affectivity and flow theories proposed that low to moderate levels of impulsivity are driven by reduced self-control or a failure of self-regulatory mechanisms. The present study confirms the above proposition. Second, the present study also contributes to the literature by confirming that impulse buying tendency can be viewed as a two-dimensional concept with both affective and cognitive dimensions, and illustrates that impulse purchase behavior is explained mainly by affective impulsivity, not by cognitive impulsivity. Third, the current study accommodates new constructs such as psychological wellbeing and NFCC as potential influencing factors in the research model, thereby contributing to the existing literature. Fourth, by incorporating multi-dimensional concepts such as psychological wellbeing and NFCC, more diverse aspects of consumer information processing can be evaluated. Fifth, the current study also extends the existing literature by confirming the two competing routes of normative and informational influences. Normative influence occurs when individuals conform to the expectations of others or to enhance his/her self-image. Whereas informational influence occurs when individuals search for information from knowledgeable others or making inferences based upon observations of the behavior of others. The present study shows that these two competing routes of social influence can be attributed to different sources of influence power. The current study also has many practical implications. First, it suggests that people with affective impulsivity may be primary targets to whom companies should pay closer attention. Cultivating a more amenable and mood-elevating shopping environment will appeal to this segment. Second, the present results demonstrate that NFCC is closely related to the cognitive dimension of impulsivity. These people are driven by careless thoughts, not by feelings or excitement. Rational advertising at the point of purchase will attract these customers. Third, people susceptible to normative influences are another potential target market. Retailers and manufacturers could appeal to this segment by advertising their products and/or services as products that can be used to identify with or conform to the expectations of others in the aspiration group. However, retailers should avoid targeting people susceptible to informational influences as a segment market. These people are engaged in an extensive information search relevant to their purchase, and therefore more elaborate, long-term rational advertising messages, which can be internalized into these consumers' thought processes, will appeal to this segment. The current findings should be interpreted with caution for several reasons. The study used a small convenience sample, and only investigated behavior in two dimensions. Accordingly, future studies should incorporate a sample with more diverse characteristics and measure different aspects of behavior. Future studies should also investigate personality traits closely related to affectivity theories. Trait variables such as sensory curiosity, interpersonal curiosity, and atmospheric responsiveness are interesting areas for future investigation.