• Journal of Korean Neurosurgical Society
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• v.30 no.5
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• pp.553-560
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• 2001

Objective : The objective of this study was to determine the photodynamic therapeutic response of U-87 human glioma cell in vitro as well as in the nude rat xenograft model using photofrin as photosensitizer. Material and Method : U-87 cells were cultured on 96-well culture plates, photofrin(Quadralogic Technologies Inc., Vancouver, Canada) was added into the cell culture medium at concentration of $1{\mu}g/ml$, $2.5{\mu}g/ml$, $5{\mu}g/ml$, $10{\mu}g/ml$ and $20{\mu}g/ml$. 24 hour after drug treatment, cells were treated with optical(632nm) irradiation of $100mJ/cm^2$, $200mJ/cm^2$ and $400mJ/cm^2$. Photofrin(12.5mg/kg, i.p.) was administered to 28 nude rats containing intracerebral U-87 human glioma as well as 26 normal nude rats. 48 hours after administration, animals were treated with optical irradiation(632nm) of $35J/cm^2$, $140J/cm^2$ and $280J/cm^2$ to exposed tumor and normal brain. The photofrin concentration was measured in tumor and normal brain in a separate population of animals. Results : By MTT assay, there was 100% cytotoxicity at any dose of photofrin with optical irradiation of $200mJ/cm^2$ and $400mJ/cm^2$. But at the optical irradiation of $100mJ/cm^2$ cells were killed in dose dependent manner 28.5%, 49.1%, 54.4%, 78.2%, and 84.6% at concentration of $1{\mu}g/ml$, $2.5{\mu}g/ml$, $5{\mu}g/ml$, $10{\mu}g/ml$ and $20{\mu}g/ml$, respectively. Dose dependent PDT lesions in both tumor and normal brain were observed. In the tumor lesion, only superficial tissue damage was found with optical irradiation of $35J/cm^2$. However, in the optical irradiation group of $140J/cm^2$ and $280J/cm^2$ the volume of lesions was measured of $7.2mm^3$ and $14.0mm^3$ for treatment at $140J/cm^2$ and $280J/cm^2$, respectively. The U-87 bearing rats showed a photofrin concentration in tumor tissue of $6.53{\pm}2.16{\mu}g/g$, 23 times higher than that found in the contralateral hemisphere of $0.28{\pm}0.15{\mu}g/g$. Conclusion : Our data indicate that the U-87 human glioma in vitro and in the xenografted rats is responsive to PDT. At these doses, a reproducible injury can be delivered to human glioma in this model. Strategies to spare the normal brain collateral damage are being studied.

• The Journal of the Korean Society for Microbiology
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• v.21 no.3
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• pp.311-329
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• 1986

The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a number of well-described changes in the recipient's immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayedtype (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms responsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviations in systemic antigen presenting cell (APC) potential. 4) changes in the production of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, causes a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a $3.0\;cm^2$ area of skin was physically protected from the light energy. Contact sensitization of these animals with DNFB, to either the irradiated or protected back skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to "protected" dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/$m^2$) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated altered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal levels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitization took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes. Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent block of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppressor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral sites of antigen challenge. Our results suggest that UVR is probably not a significant inducer of suppressor T-cell activity to topically applied antigens. Rather, UVR exposure appears to modify the normal relationship which exists between effector and regulatory immune responses in vivo. It does so by either causing a direct reduction in the skin's APC function, a situation which results in an absence of effector cell generation to antigens applied to UVR-exposed skin sites, inhibiting the capacity of effector cells to gain access to skin sites of antigen challenge or by sequestering the lymphocytes with effector cell potential into the draining peripheral lymph nodes. Each of these situations result in a similar effect on the UVR-exposed host, that being a reduced capacity to elicit a CH response. We hypothesize that altered DTH responses, altered alloresponses, and altered graft-versus-host responses, all of which have been observed in UVR exposed animals, may result from similar mechanisms.

• Microbiology and Biotechnology Letters
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• v.45 no.2
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• pp.110-117
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• 2017

The anti-inflammatory effect of Sargassum patens C. Agardh ethanol extract (SPEE) was examined based on the lipopolysaccharide (LPS)-induced inflammatory response in this study. SPEE treatment was not cytotoxic to macrophages compared to the control. The production of NO was suppressed by SPEE by approximately 28% at $100{\mu}g/ml$, and levels of interleukin-6, tumor necrosis $factor-{\alpha}$, and $interleukin-1{\beta}$ decreased in a dose-dependent manner. In addition, the expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear $factor-{\kappa}B$ was suppressed by SPEE treatment. In vivo, croton oil-induced mouse ear edema was attenuated by SPEE and the infiltration of mast cells into the tissue decreased. Based on these results, SPEE inhibits the release of LPS-induced pro-inflammatory cytokines and mediators, suggesting that SPEE is a potential agent for anti-inflammatory therapies.

• Clinical and Experimental Pediatrics
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• v.46 no.12
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• pp.1253-1259
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• 2003

Backgroud : Seizures in the neonate are relatively common and their clinical features are different from those in children and adults. The study aimed to provide the clinical profiles of neonatal seizure in our hospital. Methods : A total of 41 newborns with seizures were enrolled in this study over a period of three years. They were evaluated with special reference to risk factors, neurologic examinations, laboratory data, neuroimaging studies, EEG findings, seizure types, response to treatment, and prognosis, etc. Results : The average age at onset of seizures was $6.1{\pm}4.6days$ and the majority of patients(42%) had multifocal clonic seizure and 24% had subtle seizure. Factors that are known to increase risk of neonatal seizures include abnormal delivery history, birth asphyxia, and electrolyte imbalance, etc. However, they remain obscure in about 20% of cases. More than 50 percent showed abnormal lesions on neuroimaging studies such as brain hemorrhage, periventricular leukomalacia, brain infarction, cortical dysplasia, hydrocephalus, etc. and 17 out of 32 patients showed abnormal electroencephalographic patterns. Phenobarbital was tried as a first line antiepileptic drug and phenytoin was added if it failed to control seizures. The treatments were terminated in the majority of patients during the hospital stay. The overall prognosis was relatively good except for those with abnormal EEG background or congenital central nervous system malformations. Conclusion : Neonatal seizures may permanently disrupt brain development. Better understanding of their clinical profiles and appropriate management may lead to a reduction in neurological disability in later childhood.

• Sleep Medicine and Psychophysiology
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• v.10 no.2
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• pp.100-107
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• 2003

Objectives: Periodic leg movements in sleep (PLMS) might be subdivided based upon whether or not they are associated with visible EEG microarousals (MA). MA is considered to be responsible for nonrestorative sleep and daytime fatigue. The American Sleep Disorders Association's (ASDA) scoring rules for MA based on visual analysis of the EEG changes suggest that MA should last more than 3 seconds. However, it has been suggested that visual analysis may not detect some changes in EEG activity. This study is aimed at measuring changes in EEG spectra during PLMS without MA in order to better understand the arousing response of PLMS. Methods: Ten drug-free patients (three men and seven women) diagnosed with PLMS by polysomnography were studied. Spectral analysis of the EEG was performed in each patient on 30 episodes of PLMS without MA, chosen randomly across the night in stage 2 non-REM sleep. We applied stricter criteria for MA compared to ASDA, by defining it as a return to alpha and theta frequency lasting at least 1 second. Results: The mean PLMS index was $16.7{\pm}10.0$. The mean PLMS duration was $1.3{\pm}0.7$ seconds. Comparison of 4-second EEG activity both before and after the onset of PLMS without MA using independent t-test showed that the movements were associated with significant increase of relative activity in the delta band (p=0.000) and significant decrease of activity in the alpha (p=0.01) and sigma (p=0.000) bands. No significant decrease in the theta (p=0.05), beta (p=0.129), or gamma (p=0.062) bands was found. Conclusion: PLMS without MA was found to be associated with EEG change characterized by increase in the delta frequency band. This finding seems to be compatible with the hypothesis of an integrative hierarchy of arousal responses of Sforza's. Considering that the subjects had lower PLMS index and shorter PLMS duration than those of the previous study, it is suggested that an even less severe form of PLMS without MA could induce neurophysiologic change, which may potentially be of clinical significance.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.122-134
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• 2001

Background : Some chemotherapeutic drugs induce NF-${\kappa}B$ activation by degrading the $I{\kappa}B{\alpha}$ protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting $I{\kappa}B{\alpha}$ degradation would block NF-${\kappa}B$ activation and result in increased tumor cell mortality in response to chemotherapy. Methods : The "superrepressor" form of the NF-${\kappa}B$ inhibitor was transferred by an adenoviral vector (Ad-$I{\kappa}B{\alpha}$-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MIT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. Results : EMSA showed that $I{\kappa}B{\alpha}$-SR effectively blocked the NF-${\kappa}B$ activation induced by cisplatin. Transduction with Ad-$I{\kappa}B{\alpha}$-SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of $IC_{50}$. Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. Conclusion : The blockade of chemotherapeutics induced NF-${\kappa}B$ activation by inducing Ad-$I{\kappa}B{\alpha}$-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of $I{\kappa}B{\alpha}$-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.135-146
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• 2001

Background : One of the important mechanisms responsible for a tumor escaping the immune response is an absence of the tumor associated antigen (TAA) on the cancer cell surface. To overcome this, combination gene therapy using a herpes simplex thymidine kinase (HSTK) gene, prototype of drug sensitizing gene, was conducted to enhance T AA release by cell destruction, as well as the cytokine genes for immune cell attraction. Methods : We investigated whether or not transduction with the adenovirus-HSTK (Ad-HSTK) enhanced the sensitivity of Lewis lung carcinoma (LLC) to ganciclovir (GCV) and induced a bystander effect. A Tumor vaccine trial was performed using LLC with ad-HSTK$\pm$ad-GM-CSF$\pm$ad-IL-2 to determine if they exhibit some antitumor effect on established lung cancer xenografts. Results : LLC with ad-HSTK revealed a much higher sensitivity to ganciclovir (GCV). LLC transduced with ad-HSTK and/or ad-IL-2, ad-GM-CSF showed a lower in vivo tumorigenicity. In the treatment experiment, vaccination with LLC transduced with ad-HSTK, ad-IL-2, or ad-GM-CSF alone modestly suppressed the growth of an established tumor. Combined transduction with HSTK and GM-CSF induced stronger growth suppression of a established lung cancer, while HSTK and IL-2 combination transduction did not have any antitumor effect on individual transduction. Vaccination with LLC-HSTK-GM-CSF increased the infiltration of dendritic cells in the spleen. Conclusion : It was concluded that a tumor vaccine transduced with HSTK and GM-CSF induces strong antitumor immunity by activating the dendritic cells.

• Journal of agricultural medicine and community health
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• v.27 no.1
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• pp.155-164
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• 2002

Hypertension is the most frequent disease of chronic circulatory diseases and major intermediate cause or risk of the cerebrovascular disease which is a leading cause of death in Korea. Therefore, management of hypertension is an important issue in Korean healthcare. Especially, therapeutic compliance of hypertensives is very important because the hypertensive patients should receive anti-hypertensive treatment as long as the condition exists. However, many patients drop out of treatment, which is a major problem that needs to be solved through a hypertension control program. This study was carried out to provide basic data and counter measule for the hypertension control program in the community which aimed to keep the patients receiving treatment continuously. In order to investigate compliance of hypertensive patients during three months follow-up and the rate of control of hypertension, the data were collected during February, 2001, by reviewing medical records of 295 hypertensive patients who had been registered to Gunnam-myeon health subcenter before November, 2000. The author also study the dropout reasons by interviewing 58 patients among 68 dropout patients. The results were as follows: 1. Among the 295 subjects, 108(36.6%) were male and 187(63.4%) were female. Statistically, female hypertensives had a higher mean age than male(64.6 vs 66.3, p<0.05). 2. The 54.9% of the patients took anti-hypertensive medicine continuously for the past three months. And 19.3% had drug intermittently, and 25.8% dropped out of treatment. 3. Among several variables, such as sex, age, health insurance, the time taken from a patient's village to the health subcenter, only the last one was found to be significantly related to therapeutic compliance in the contingency table analysis. 4. The dropout reasons by multiple response were as follows, 'no symptom or no problem' (23.9%), 'change to other hospitals'(19.4%), 'geographical barrier'(17.9%), 'change to a neighborhood drugstore' (14.9%), 'immobility'(7.5%), 'economic barrier'(6.0%), 'unsatisfactory services of the health subcenter'(4.4%). 5. The mean blood pressure of 295 subjects was $144.9{\pm}12.9/86.88{\pm}8.6mmHg$. 6. The 32.5% of the subjects were controlled below 140/90mmHg. Conclusions: In order to improve the low rates of treatment and control of hypertension in rural hypertensives, a more active and systematic hypertension control program, including out-reaching follow-up management, is required in rural area. Especially, for health education of hypertensive patients, emphasis should placed on correcting wrong attitude toward hypertension.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.29-34
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• 1993

Experiments have been carried out with C3H mouse fibrosarcoma (FSa II) to determine the effect of different sequence and time intervals between irradiation and administration of cis-diammihedichloroplatinum (cis-DDP) with gross tumors (6 mm in diameter), microscopic tumors (3 days after transplantation of $10^3$ cells) and cells in culture. The drug was administered either 24, 12, 8, 4, 2, 1, 0.5 hour before irradiation, immediately before irradiation, or 0.5, 1, 2, 4, 8, 12, 24 hours after irradiation. In case of in vivo studies, tumor growth delay was used as an end point. Clonogenic cell surviving fraction was used for in vitro studies. Tumor growth delay for gross tumor after 10 Gy radiation plus 10 mg/kg cis-DDP ranged from 6.3 to 10.66 days and the enhancement ratio ranged from 1.37 to 2.23. The most effective combination was when cis-DDP was given 4 hours before irradiation. Tumor growth delay for microscopic tumor after 5 Gy of radiation and 5 mg/kg of cis-DDP ranged from 3.55 to 11.98 days with enhancement ratio from 2.05 to 6.92. Microscopic tumors showed response significantly greater than additive in every time interval and the most effective treatments were when cis-DDP was given 2 and 1 hour before irradiation. In in vitro experiment, the surviving fraction after 6 Gy of radiation and 1 hour exposure to 4 ${\mu}M$ cis-DDP fluctuated as a function of time between treatments, but the difference between maximum and minimum surviving fractions was very small. According to the above results the sequence and time interval between irradiation and chemotherapy is very critical especially for the management of microscopic tumors as in the case of postoperative adjuvant treatment.

• Pediatric Infection and Vaccine
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• v.12 no.1
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• pp.75-85
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• 2005

Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.