• Korean Journal of Radiology
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• v.22 no.3
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• pp.366-375
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• 2021

Objective: To evaluate the radiological tumor response patterns and compare the response assessments based on immune-based therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST 1.1 in metastatic clear-cell renal cell carcinoma (mccRCC) patients treated with programmed cell death-1 (PD-1) inhibitors. Materials and Methods: All mccRCC patients treated with PD-1 inhibitors at Henan Cancer Hospital, China, between January 2018 and April 2019, were retrospectively studied. A total of 30 mccRCC patients (20 males and 10 females; mean age, 55.6 years; age range, 37-79 years) were analyzed. The target lesions were quantified on consecutive CT scans during therapy using iRECIST and RECIST 1.1. The tumor growth rate was calculated before and after therapy initiation. The response patterns were analyzed, and the differences in tumor response assessments of the two criteria were compared. The intra- and inter-observer variabilities of iRECIST and RECIST 1.1 were also analyzed. Results: The objective response rate throughout therapy was 50% (95% confidence interval [CI]: 32.1-67.9) based on iRECIST and 30% (95% CI: 13.6-46.4) based on RECIST 1.1. The time-to-progression (TTP) based on iRECIST was longer than that based on RECIST 1.1 (median TTP: not reached vs. 170 days, p = 0.04). iRECIST and RECIST 1.1 were discordant in 8 cases, which were evaluated as immune-unconfirmed PD based on iRECIST and PD based on RECIST 1.1. Six patients (20%, 6/30) had pseudoprogression based on iRECIST, of which four demonstrated early pseudoprogression and two had delayed pseudoprogression. Significant differences in the tumor response assessments based on the two criteria were observed (p < 0.001). No patients demonstrated hyperprogression during the study period. Conclusion: Our study confirmed that the iRECIST criteria are more capable of capturing immune-related atypical responses during immunotherapy, whereas conventional RECIST 1.1 may underestimate the benefit of PD-1 inhibitors. Pseudoprogression is not rare in mccRCC patients during PD-1 inhibitor therapy, and it may last for more than the recommended maximum of 8 weeks, indicating a limitation of the current strategy for immune response monitoring.

• Progress in Medical Physics
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• v.25 no.3
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• pp.143-150
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• 2014

In general radiotherapy, mega-voltage (MV) x-ray images are widely used as the unique method to verify radio-therapeutic fields. But, the image quality of MV images is much lower than that of kilo-voltage x-ray images due to scatter interactions. Since 1990s, studies for the scatter correction have performed with digital-based MV imaging systems. In this study, a novel method for the scatter correction is suggested using scatter to primary ratio (SPR), instead of conventional methods such as digital image processing or scatter kernel calculations. We measured two MV images with and without a solid water phantom describing a patient body with given imaging conditions, and calculated un-attenuated ratios. Then, we obtained SPR distributions for the scatter correction. For experimental validation, a line-pair (LP) phantom using several Al bars and a clinical pelvis MV image was used. As the result, scatter signals of the LP phantom image were successfully reduced so that original density distribution of the phantom was restored. Moreover, image contrast values increased after SPR correction at all ROIs of the clinical image. The mean value of increases was 48%. The SPR correction method suggested in this study has high reliability because it is based on actually measured data. Also, this method can be easily adopted in clinics without additional cost. We expected that the SPR correction can be an effective method to improve the quality of MV image guided radiotherapy.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.39-51
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• 1995

The roles of ${\beta}-adrenoceptor$ were well known in hyperthyroidal heart, but not with ${\alpha}-adrenoceptor$. So we studied the effects of phenylephrine on membrane potential, intracellular sodium activity ($a^{i}_{Na}$), twitch force, and intracellular pH ($pH_i$) by continuous intracellular recordings with ion-selective and conventional microelectrodes in the papillary muscles of hyperthyroid guinea pig heart. ${\alpha}_1-adrenoceptor$ stimulation by phenylephrine (10^{-5}\;or\;3{\times}10^{-5}M$) produced the following changes: variable changes in action potential duration, a hyperpolarization ($1.5{\pm}0.1mM$) of the diastolic membrane potential, an increase in $a^{i}_{Na}\;(0.4{\pm}0.15mM)$, a stronger positive inotropic effect ($220{\pm}15%$), an increase in $pH_i\;(0.06{\pm}0.002\;unit)$. These changes were flocked by prazosin and atenolol. This indicated that the changes in membrane potential, $a^{i}_{Na}$ twitch force, and $pH_i$ are mediated by a stimulation of the ${\alpha}_1-adrenoceptor$. Ethylisopropylamiloride ($10^{-5}$) also blocked the increase in $a^{i}_{Na}$ and twitch force. On the other hand, strophanthidin, tetrodotoxin, $Cs^+$ or verapamil did not block the increase in $a^{i}_{Na}$ and twitch force. Thus, it was suggested that ${\alpha}_1-adrenoceptor$ stimulation increased $a^{i}_{Na}\;and\;pH_i$ by stimulation of $Na^{+}-H^{+}$ exchange, thereby allowing intracellular alkalinization and $a^{i}_{Na}$ increase. These results were very different from euthyroidal heart which showed ${\alpha}_1-adrenoceptor$-induced decrease in $a^{i}_{Na}$ and initial negative inotropic effect. From the above results, it was concluded that ${\alpha}_1-adrenoceptor$ had a important role in hyperthy-roidal heart.

• Journal of Life Science
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• v.26 no.11
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• pp.1313-1319
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• 2016

Cancer is a complex disease heterogeneously composed of various types of cells including cancer stem-like cells responsible for relapse and chemoresistance in the tumor microenvironment. The conventional two-dimensional cell culture-based platform has critical limitations for representing the heterogeneity of cancer cells in the three-dimensional tumor niche in vivo. To overcome this insufficiency, three-dimensional cell culture methods in a scaffold-dependent or -free physical environment have been developed. In this study, we improved and simplified the HCT-8 colon cancer cell-based spheroid culture protocol and evaluated the relationship between cancer stemness and responses of chemosensitivity to 5- Fluorouracil (5-FU), a representative anticancer agent against colon cancer. Supplementation with defined growth factors in the medium and the culture dish of the regular surface with low attachment were required for the formation of constant-sized spheroids containing $CD44^+$ and $CD133^+$ colon cancer stem cells. The chemo-sensitivities of $CD44^+$ cancer stem cells in the spheroids were much lower than those of $CD44^-$ non-stem-like cancer cells, indicating that the chemoresistance to 5-FU is due to the stemness of colon cancer cells. Taken together, the inflammation and oncogenic gut environment-sensitive HCT-8 cell-based colon cancer spheroid culture and comparative evaluation using the simplified model would be an efficient and applicable way to estimate colon cancer stemness and pharmaceutical response to anticancer drugs in the realistic tumor niche.

• Progress in Medical Physics
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• v.19 no.4
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• pp.269-275
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• 2008

Although MR imaging is generally applicable to depict knee joint deterioration it, is sometimes occurred to mis-read and mis-diagnose the common knee joint diseases. In this study, we employed magnetization transfer ratio (MTR) method to improve the diagnosis of the various knee joint diseases. Spin-echo (SE) T2-weighted images (TR/TE 3,400-3,500/90-100 ms) were obtained in seven cases of knee joint deterioration, FSE T2-weighted images (TR/TE 4,500-5,000/100-108 ms) were obtained in seven cases of knee joint deterioration, gradient-echo (GRE) T2-weighted images (TR/TE 9/4.56/$50^{\circ}$ flip angle, NEX 1) were obtained in 3 cases of knee joint deterioration, In six cases of knee joint deterioration, fat suppression was performed using a T2-weighted short T1/tau inverse recovery (STIR) sequence (TR/TE =2,894-3,215 ms/70 ms, NEX 3, ETL 9). Calculation of MTR for individual pixels was performed on registration of unsaturated and saturated images. After processing to make MTR images, the images were displayed in gray color. For improving diagnosis, three-dimensional isotropic volume images, the MR tristimulus color mapping and the MTR map was employed. MTR images showed diagnostic images quality to assess the patients' pathologies. The intensity difference between MTR images and conventional MRI was seen on the color bar. The profile graph on MTR imaging effect showed a quantitative measure of the relative decrease in signal intensity due to the MT pulse. To diagnose the pathologies of the knee joint, the profile graph data was shown on the image as a small cross. The present study indicated that MTR images in the knee joint were feasible. Investigation of physical change on MTR imaging enables to provide us more insight in the physical and technical basis of MTR imaging. MTR images could be useful for rapid assessment of diseases that we examine unambiguous contrast in MT images of knee disorder patients.

• Applied Microscopy
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• v.35 no.1
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• pp.31-39
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• 2005

Synapses are contact points where one neuron communicates with another. The morphological change of synapses under various physiological or pathological conditions has long been hypothesized to modify their functional properties. 3-dimensional (3-D) reconstruction of synapses with serial ultrathin sections has contributed to the understanding of ultrastructural dimensions and compositions of synapses. The 3-D reconstruction procedures, however, require a great amount of expertise as well as include prohibitively timeconsuming processes. Here, we introduce efficient 3-D reconstruction technique using high-voltage electron microscopy (HVEM). Primarily, we established an optimal section thickness and staining condition to observe synaptic structures in detail under HVEM. The result showed that synaptic profiles were preserved at the section thickness of 250 nm without the overlapping of synaptic ultrastructures. An increase in the reaction time of en bloc staining was most efficient to enhance contrast than the extension of postembedding staining or the addition of uranyl acetate during dehydration. Then, 3-D reconstruction of parallel fiber-Purkinje cell synapses in the rat cerebellum was carried out with serial HVEM images and reconstruction software. The images were aligned and the contours of synapses were outlined on each section. 3-D synapses were finally extracted from the section files by grouping all the synaptic contours. The reconstructed synapse model clearly demonstrated the configuration of pre and postsynaptic components. These results suggest that 3-D reconstruction of synapses using HVEM is much efficient and suitable for massive quantitative studies on synaptic connectivity than conventional TEM approach using numerous ultrathin sections.

• Clinical and Experimental Reproductive Medicine
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• v.21 no.1
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• pp.31-41
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• 1994

Morphological estimation of human spermatozoa is complicated by the fact that there is great natural variation in shape. This natural variation in shapes makes it difficult to say which forms are associated with infertility and which are normal variations. Possibly post coital test or in vitro cervical mucus penetration tests will help to clarify this question by showing which sperm are capable of penetration. The purpose of this investigation was performed to assess distribution of various morphological abnormalities according to the ability of sperm to penetrate cervical mucus. The sperm-mucus penetration using hen's egg white as substituting mucus for human cervical mucus was done in 45 fertile men with normal semen analysis and 122 infertile men with abnormal seminal parameters more than one. The female partners of 122 infertile couples showed normal results in the female fundamental test for fertility. Conventional semen analysis was evaluated according to the WHO standard normal(l980). The detailed classification of the abnormal sperm was made according to David et al(l975). The vitality of the sperm samples determined by eosin yellow-nigrosin stainig according to the method of Eliasson(l977). Results were as follw; 1. The patients had significantly lower total sperm count, motility (%), normal morphology (%), viability and total functional sperm fractions(TFSF) than fertile donors. 2. The mean value of sperm penetration distance of the patients(28.69${\pm}$11.02mm) showed significantly lower than fertile donors(37.33${\pm}$5.49mm). And 43/45 fertile donors(95.5%) as well as 57/122 patients(46.7%) had over 30mm in sperm penetration distance respectively. While 2/45 fertile donors(4.5 %) and 65/122 patient(53.3%) had under 30mm in sperm penetration distance respectively. 3. The morphological abnormalities in fertile donors were significantly lower 23.04${\pm}$5.83% (head = 12.89${\pm}$4.98, neck=6.11${\pm}$3.83%, and tail=3.43${\pm}$2.65%), compared to 36.03${\pm}$14. 40% in patients(head = 15.98 8.60%, neck 11.20${\pm}$6.56% and tail=8.70${\pm}$6.55%). Also, 3 types of sperm abnormalities including head, neck and tail were significantly lower in patient than fertile donors, respectively. Both the patients and fertile donors showed higher distribution of sperm with abnormal head than abnormal neck and tail. 4. The mean morphological abnormalities(SP>30mm) of the patients(30.68 11.64%; head = 15.95${\pm}$9.35%, neck=8.14${\pm}$4.21 %, tail=6.56${\pm}$5.64%) were significantly lower compared to patients(40.72${\pm}$15.01 %; head=16.02${\pm}$7.69%, neck 13.89${\pm}$7.82%, tail=1O.58${\pm}$6.75%) under 30mm in sperm penetration distance. Also, both groups over 30mm and under 30mm in sperm penetration showed distance higher distribution of sperm with abnormal head than abnormal neck and tail. The morphological abnormalities of head did not show significant difference but abnormal neck and tail were significant difference between the over 30mm and under 30mm group in sperm penetration distance.

• The Korean Journal of Physiology
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• v.18 no.1
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• pp.19-35
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• 1984

Since the first report of Drury and $Szent-Gy{\ddot{o}}rgyi$ in 1929, the inhibitory influences of adenosine on the heart have repeatedly been described by many investigators. These studies have shown that adenosine and adenine nucleotides have overall depressant effects, similar to those of acetylcholine. Heart beats become slow and weak. It is also well known that adenosine is a potent endogenous coronary vasodilator. Many investigations on the working mechanisms of adenosine have been focused mainly on the effects of the coronary blood flow. However, the cellular mechanisms underlying the inhibitory action of adenosine on sinus node are not well understood yet. Thus, this study was undertaken to examine the behavior of rabbit SA node under influence of adenosine. In these series of experiments three kinds of preparations were used: whole atrial pair, left atrial strip, and isolated SA node preparations. The electrical activity of SA node was recorded with conventional glass microelectrodes 30 to 50 $M{\Omega}$. The preparations were superfused with bicarbonate-buffered Tyrode solution of pH 7.35 and aerated with a gas mixture of $3%\;CO_2-97%\;O_2$ at $35^{\circ}C$. In whole atrial pair, adenosine suppressed sinoatrial rhythm in a dose-dependent manner. Effect of adenosine on atrial rate appeared at the concentration of $10^{-5}M$ and was enhanced in parallel with the increase in adenosine concentration. Inhibitory action of adenosine on pacemaker activity was more prominent in the preparation pretreated with norepinephrine, which can steepen the slope of pacemaker potential by increasing permeability of $Ca^{+2}$. Calcium ions in perfusate slowly produced a marked change in sinoatrial rhythm. Elevation of the calcium concentration from 0.3 to 8 mM increased the atrial rate from 132 to 174 beats/min, but over 10 mM $Ca^{+2}$ decreased. The inhibitory effect of adenosine on sinoatrial rhythm developed very rapidly. Atrial rate was recovered promptly from the adenosine-induced suppression by the addition of norepinephrine, but extra $Ca^{+2}$ was less suitable to restore the suppression of atrial rate. Adenosine suppressed also atrial contractility in the same dosage range that restricted pacemaker activity, even in the reserpinized preparation. In isolated SA node preparation, spontaneous firing rate of SA node at $35^{\circ}C$(mean{\pm}SEM, n=16) was $154{\pm}3.3\;beats/min. The parameters of action potentials were: maximum diastolic potential(MDP), $-73{\pm}1.7\;mV: overshoot(OS), $9{\pm}1.4\;mV: slope of pacemaker potential(SPP), $94{\pm}3.0\;mV/sec. Adenosine suppressed the firing rate of SA node in a dose-dependent manner. This inhibitory effect appeared at the concentration of $10^{-6}M$ and was in parallel with the increase in adenosine concentration. Changes in action potential by adenosine were dose-dependent increase of MDP and decrease of SPP until $10^{-4}M$. Above this concentration, however, the amplitude of action potential decreased markedly due to the simultaneous decrease of both MDP and OS. All these effects of adenosine were not affected by pretreatment of atropine and propranolol. Lowering extra $Ca^{2+}$ irom 2 mM to 0.3 mM resulted in a marked decrease of OS and SPP, but almost no change of MDP. However, increase of perfusate $Ca^{2+}$ from 2 mM to 6 or 8 mM produced a prominent decrease of MDP and a slight increase of OS and SPP. Dipyridamole(DPM), which is known to block the adenosine transport across the cell membrane, definately potentiated the action of adenosine. The results of this experiment suggest that adenosine suppressed pacemaker activity and atrial contractility simultaneously and directly, by decreasing $Ca^{2+}-permeability$ of nodal and atrial cell membranes.

• The Journal of Korean Academy of Prosthodontics
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• v.53 no.3
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• pp.207-214
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• 2015

Due to the limitations of conventional removable partial denture prostheses to treat a cleft lip & palate patient who shows scar tissue on upper lip, excessive absorption of the maxillary residual alveolar ridge, and class III malocclusion with narrow palate and undergrowth of the maxilla, 4 implants were placed on the maxillary edentulous region and a maxillary removable implant-supported partial denture was planned using a CAD/CAM milled titanium bar. Unlike metal or gold casting technique which has shrinkage after the molding, CAD/CAM milled titanium bar is highly-precise, economical and lightweight. In practice, however, it is very hard to obtain accurate friction-fit from the milled bar and reduction in retention can occur due to repetitive insertion and removal of the denture. Various auxiliary retention systems (e.g. $ERA^{(R)}$, $CEKA^{(R)}$, magnetics, $Locator^{(R)}$ attachment), in order to deal with these problems, can be used to obtain additional retention, cost-effectiveness and ease of replacement. Out of diverse auxiliary attachments, $Locator^{(R)}$ has characteristics that are dual retentive, minimal in vertical height and convenient of attachment replacement. Drill and tapping method is simple and the replacement of the metal female part of $Locator^{(R)}$ attachment is convenient. In this case, the $Locator^{(R)}$ attachment is connected to the milled titanium bar fabricated by CAD/CAM, using the drill and tapping technique. Afterward, screw holes were formed and 3 $Locator^{(R)}$ attachments were secured with 20 Ncm holding force for additional retention. Following this procedure, satisfactory results were obtained in terms of aesthetic facial form, masticatory function and denture retention, and I hereby report this case.

• Journal of radiological science and technology
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• v.32 no.4
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• pp.461-469
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• 2009

To predict the tumor grading, various imaging modalities have been applied clinically. This study determines clinical usefulness of perfusion MRI, using relative cerebral blood volume in grading of the gliomas. We did a retrospective review of 17 patients (mean age, 57.5 years; 11 male, 6 female) who underwent perfusion MR and conventional MRI, and then correlated pathologically after operation. Statistical analysis of regional cerebral blood volume and relative cerebral blood volume(rCBV) was performed by using softwares such as PAT by SIEMENS and Xmap ver 2.0 developed by ourselves. Six patients out of 13 were low-grade gliomas while eleven patients were the high-grade gliomas. Mean relative CBV (m_rCBV/white matter) in the low-grade gliomas was 1.62, and mean relative CBV(m_rCBV/cortex) was 0.12. In the high-grade gliomas, mean relative CBV(m_rCBV/white matter) and mean relative CBV(m_rCBV/cortex) were 33.53 and 0.96. Mean relative CBV of gliomas were elevated with a statistical difference(P<.05), compared with contralateral white matter(P=.019) or cortex(P=.025). Furthermore mean relative CBV(m_rCBV/white matter) was much higher than mean relative CBV(m_rCBV/cortex). Perfusion MRI using regional cerebral blood volume and rCBV is very useful imaging modality for grading the glioma.