• Journal of Life Science
• /
• v.32 no.2
• /
• pp.175-188
• /
• 2022

Relaxin has been demonstrated to have regulatory functions on both the smooth muscle and extracellular matrix (ECM) of blood vessels and fibrotic organs. The diverse mechanisms by which relaxin acts on small resistance arteries and fibrotic organs, including the bladder, are reviewed here. Relaxin induces vasodilation by inhibiting the contractility of vascular smooth muscles and by increasing the passive compliance of vessel walls through the reduction of ECM components, such as collagen. The primary cellular mechanism whereby relaxin induces arterial vasodilation is mediated by the endothelium-dependent production of nitric oxide (NO) through the activation of RXFP1/PI3K, Akt phosphorylation, and eNOS. In addition, relaxin triggers different alternative pathways to enhance the vasodilation of renal and mesenteric arteries. In small renal arteries, relaxin stimulates the activation of the endothelial MMPs and EtB receptors and the production of VEGF and PlGF to inhibit myogenic contractility and collagen deposition, thereby bringing about vasodilation. Conversely, in small mesenteric arteries, relaxin augments bradykinin (BK)-evoked relaxation in a time-dependent manner. Whereas the rapid enhancement of the BK-mediated relaxation is dependent on IK_Ca channels and subsequent EDH induction, the sustained relaxation due to BK depends on COX activation and PGI₂. The anti-fibrotic effects of relaxin are mediated by inhibiting the invasion of inflammatory immune cells, the endothelial-to-mesenchymal transition (EndMT), and the differentiation and activation of myofibroblasts. Relaxin also activates the NOS/NO/cGMP/PKG-1 pathways in myofibroblasts to suppress the TGF-β1-induced activation of ERK1/2 and Smad2/3 signaling and deposition of ECM collagen.

• Journal of Yeungnam Medical Science
• /
• v.11 no.2
• /
• pp.293-302
• /
• 1994

The objective of this study was to establish a good methodology to isolate single smooth muscle cells that are alive and respond properly to pharmacological agents. Canine urinary bladders were employed as the source of single cells, and acetylcholine, atropine and imipramine were used as indicators of pharmacological responsiveness. Imipramine, an antidepressant drug exhibited the anticholinergic and calcium antagonizing properties on rat detrusor muscle. To establish a control value for a further experiment to elucidate the mechanism of action of imipramine on detrusor muscle, we measured the concentration-response of single cells to acetylcholine in the presesnce of imipramine by length of the cells and compared the result with the response in the presence of atropine. Tiny chops of smooth muscle taken from anesthetized canine urinary bladder were incubated in collagenase solution at $36^{\circ}C$ for 17-20 minutes. The collagenase solution included collagenase 1.2 mg/ml, soybean tryspin inhibitor 0.08 mg/ml, bovine serum albumin 2% in 10 ml Krebs-Henseleit buffer solution aerated with a consistent breeze of 95/5% $O_2/CO_2$, to maintain the pH at 7.4. After washing with plain K-H solution on 450 mesh, cells were dissociated from the digested tissue for 12-15 minutes. Cell suspension was transfered in 5 ml test tubes and acetylcholine was added for the final concentration to be $10^{-14}M{\sim}10^{-9}M$. To find the optimal time to fix the cells to determine the contractile responses, 1% acrolein was added 5, 10, 20, 30, 60 and 120 seconds after the administration of ACh. The length of cells fixed by acrolein were measured by microscaler via CCTV camera on phaes-contrast microscope. The average length of 50 cells from a slide glass was taken as the value of a sample at the very concentration point. Single cells were isolated from canine detrusor. The length of untreated cells varied from 82 ${\mu}m$ to 94 ${\mu}m$. The maximal response to actylcholine $10^{-9}M$ was accomplished within 5 seconds of exposure, and the shortening was $19{\pm}3$%. Atropine reduced the contraction of the cells concentration-dependently. Imipramine which exerts a cholinergic blocking action on some smooth muscles also reduced the contraction concentration-dependently and by a similar pattern as atropine. These findings document that imipramine may exerts a cholinergic blocking activity in the single smooth muscle cells isolated from canine urinary bladder.

• Radiation Oncology Journal
• /
• v.19 no.4
• /
• pp.301-305
• /
• 2001

Purpose : This study was peformed for the evaluation of the feasibility and toxicity of hypofractionated radiation therapy for early glottic cancer Methods and Materials : From February 1999 to February 2000, 20 patients with Histologically confirmed Stage I, II glottic cancer were enrolled into this study. There were 18 males and 2 females, the median age of the patients was 59 years. The distribution of stage distribution was as fellows; T1aN0-16 patients, T1bN0-1 patient, T2N0-3 patients. Eighteen patients underwent laryngomicroscopic biopsy only, and two patients underwent laser cordectomy. All patients received radical radiation therapy (2.5 Gy per fraction, 24 fractions, total 60 Gy). Median duration of treatment was 36 days (range $31\~45\;days$). Results : Radiation therapy were well tolerated. Most common acute reactions were odynophagia and hoarseness, and these reactions resolved after radiation therapy. There were one case of RTOG grade 3 odynophagia $(5\%)$, six cases of grade 3 hoarseness $(30\%)$. Response of radiation therapy was evaluated one month after completion of treatment. All patients revealed complete response. During follow up, total three cases of treatment failure were detected. two cases were local recurrence in 10 and 13 months of radiation therapy and one case was local recurrence and distant metastasis in 2 months of radiation therapy. Conclusion : This hypofractionated radiation therapy schedule was feasible and effective for control of early glottic cancer But longer follow up time would be required to assess the long-term disease control and the late complication by shortening radiation therapy duration.

• Radiation Oncology Journal
• /
• v.11 no.2
• /
• pp.387-395
• /
• 1993

To identify pretreatment prognostic factors in carcinoma of the uterine cervix, a retrospective analysis was undertaken of 510 patients treated with curative radiation therapy in Seoul National University Hospital during the 7 year period, from March 1979 through December 1986. According to FIGO classification,35 patients were stage I B,89 were stage IIA, 232 were stage IIB,8 were stage IIIA, 134 were IIIB, and 12 were stage IVA. Five year locoregional control (LRC) rates in stage I B, II A, II B, IIIA, IIIB, and IVA were $79\%,78\%,70\%,58\%,51\%\;and\;27\%,$ respectively. Five year disease free survival (DFS) rates were $76\%,67\%,60\$,57\%,40\%,\;and\;25\%,$ respectively. Overall survival (OS) rates at five years were $82\%,72\%,67\%,67\%,51\%,\;and\;33\%,$ respectively. In univariate analyses, stage, age, initial hemoglobin level, type of histology, tumor size, and several CT findings including pelvic lymph node (LN) status, paraaortic lymph node (PAN) status, extent of parametrial invasion, bladder invasion, and rectal invasion were significant factors in terms of LRC. All these factors and elevation of BUN or creatinine were associated with DFS. In terms of overall survival, stage, initial hemoglobin level, type of histology, tumor size, elevation of BUN or creatinine, and five CT findings associated with LRC were prognostically significant. In multivariate analysis excluding CT findings, stage IV disease, non-squamous histology, and tumor size $\ge$4 cm were associated with poor LRC and DFS. Stage IV disease and tumor size significantly affected OS. in multivariate analysis including CT findings, histology, tumor size, and pelvic LN status on CT were uniformly significant in terms of LRC, DFS, and 05, PAN status on CT affected overall survival only.

• Journal of Life Science
• /
• v.25 no.8
• /
• pp.849-860
• /
• 2015

The anti-cancer activities of Rhus verniciflua Stokes (GC), Ulmus davidiana var. japonica Nakai (UGP) and arsenium sublimatum (SS) extracts, which have been used Oriental medicine therapy for various diseases, were investigated. The treatment of GC, UGP and SS alone, and combined treatment with GC, UGP and SS did not affect the cell viability in the mouse normal cell lines (RAW 264.7 macrophages and C2C12 myoblasts). However, co-treatment with GC, UGP and SS markedly induces apoptosis in human gastric cancer AGS cells, but not in other various cancer cell lines (human lung cancer A549, colon cancer HCT116, liver cancer Hep3B and bladder T24 cells) as evidenced by formation of apoptotic bodies, chromatin condensation, and accumulation of annexin-V positive cells. Co-treatment with GC, UGP and SS effectively induced the expression levels of Fas and Fas ligand, and inhibited the levels IAP family proteins such as XIAP, cIAP-1 and survivin, and anti-apoptotic Bcl-xL proteins compared with treatment with either agent alone. Combined treatment also significantly induced the loss of mitochondrial membrane potential, which was associated with the activation of caspases (-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase. However, the cytotoxic effects induced by co-treatment with GC, UGP and SS were significantly attenuated by pan-caspases inhibitor, z-VAD-fmk, indicating an important role for caspases. These results indicated that the caspases were key regulators of apoptosis in response to co-treatment of GC, UGP and SS in human gastric cancer AGS cells and further studies will be needed to identify the active compounds.

• Journal of Korean Medical classics
• /
• v.24 no.3
• /
• pp.65-70
• /
• 2011

문헌(文獻)에 기재된 내용을 근거로 병맥주병(病脉主病)을 단맥(單脈)과 상겸맥(相兼脈)을 구분하는 입장에서 연구하는 것이 단맥(單脈), 상겸맥(相兼脈)이 혼재하는 맥진학(脈診學) 분야에서 병맥주병(病脈主病) 연구에 도움이 된다고 생각되어, 먼저 부맥주병(浮脈主病)을 중심으로 단맥주병(單脈主病)과 상겸맥주병(相兼脈主病) 연구에 임하게 되었다. 부맥(浮脈) 병맥주병(病脉主病)을 단맥(單脈)과 상겸맥(相兼脈)으로 구분하여 조사한 결과, 다음과 같은 지견을 얻을 수 있었다. 맥진(脈診) 제가(諸家)는 이론적인 입장보다는 임상적인 자료에 근거한 실용적(實用的)인 입장(立場)으로서, 좌우수(左右手) 촌관척(寸關尺)의 부맥(浮脈)의 단맥주병(單脈主病)은 외감(外感) 호흡기(呼吸器) 증상(症狀)으로, 촌관척(寸關尺) 6부위별(部位別) 단독 부맥(浮脈) 단맥주병(單脈主病)은 촌관척(寸關尺)의 장상론적(藏象論的)인 증상(症狀)으로 관찰하였으며, 오장(五臟) 육부(六腑) 촌관척(寸關尺) 배속(配屬)의 입장에서는 대장(大腸)과 방광(膀胱)을 척부(尺部)에서 진맥(診脈)하는 실용적인 입장을 보였다. 제가(諸家)들은 부맥(浮脈) 상겸맥(相兼脈) 주병(主病)에서 대(大), 홍(洪), 완(緩), 긴(緊), 삽(澁), 삭(數), 지(遲), 허맥(虛脈)을 높은 빈도(頻度)의 상겸맥(相兼脈)으로 취급하고 있으며, 장(長), 활(滑), 세(細), 질(疾), 단(短), 芤, 미(微), 유(濡), 현(弦), 산맥(散脈)을 낮은 빈도(頻度)의 상겸맥(相兼脈)으로 다루고 있다. 또한 기본(基本) 단일(單一) 맥상(脈象)으로는 대(大), 삽(澁), 삭(數), 지(遲), 허(虛), 장(長), 활(滑), 세(細), 질(疾), 단(短), 현(弦), 산맥(散脈)이, 두개 이상(以上)의 맥(脈)이 결합(結合)된 합병맥상(合幷脈象)으로는 홍(洪), 완(緩), 긴(緊), 규(芤), 미(微), 유맥(濡脈)이 부맥(浮脈) 상겸맥(相兼脈)으로 주로 다루어지고 있다. 부대(浮大), 부장(浮長), 부완(浮緩), 부세(浮細), 부긴(浮緊), 부단(浮短), 부삭(浮數), 부허(浮虛), 부미(浮微), 부현(浮弦)의 상겸맥(相兼脈)은 맥위상(脈位上)으로 부맥(浮脈)의 속성(屬性)을 합리적으로 인정(認定)하는 상겸맥(相兼脈)으로 판단되나, 홍맥(洪脈), 허맥(虛脈), 규맥(芤脈), 유맥(濡脈)과의 부맥(浮脈) 상겸맥(相兼脈)은 이미 갖추고 있는 부맥(浮脈) 속성(屬性)에 또 다시 부맥(浮脈)과 상겸(相兼)하는 중복성(重複性)의 문제가 있으므로, 앞으로 부맥(浮脈)의 단맥(單脈)과 상겸맥(相兼脈) 주병(主病)에서 보다 깊은 연구가 있어야 할 것으로 생각한다.

• Journal of the Korean Society of Environmental Restoration Technology
• /
• v.8 no.1
• /
• pp.73-78
• /
• 2005

It was aimed to promote Cyrtomium falcatum as a material for interior landscape by validating it indoor adaptability in the indoor environment, especially irrigation times, soil treatment and drainage level. Irrigation times were 2 times per week and 7 times per week. Soil treatment and drainage level were carried out drainage-peatmoss : vermiculite : perlite=1 : 1 : 1(D-PVP), peatmoss : vermiculite : perlite=1 : 1 : 1(PVP), drainage-saprolite : leaf mold=1 : 1(D-SL) and saprolite : leaf mold=1 : 1(SL). 1. Top of growth was better with irrigation 7 times per week than irrigation 2 times per week but indoor adaptability was decreased and shown yellowish green. 2. In case of soil treatment, growth was better with saprolite : leaf mold=1 : 1 but indoor growth adaptability was decreased than peatmoss : vermiculite : perlite=1 : 1 : 1. 3. Plant height and blade length were increased under non-drainage treatment but indoor adaptability, number of new fronds and number of sporophyll were decreased under drainage treatment, regardless of irrigation times and soil treatment. 4. Photosynthetic rate(Pn) was the highest in the drainage-peatmoss : vermiculite : perlite=1 : 1 : 1 treatment of irrigation 2 times per week and was the lowest in the saprolite : leaf mold=1 : 1 treatment of irrigation 7 times per week.

• Journal of Life Science
• /
• v.23 no.10
• /
• pp.1252-1259
• /
• 2013

To investigate the effects of a fibrinolytic enzyme, BK-17, on the growth of human cancer cells, we performed various biochemical experiments, including cell proliferation and viability, and investigated subsequent morphological changes and apoptosis induction. BK-17 treatment of AGS human gastric and T24 human bladder carcinoma cells decreased the viability and the proliferation of the cells in a concentration-dependent manner. Microscopic studies indicated that the antiproliferative effects of the BK-17 treatment were associated with morphological changes, such as membrane shrinking, cell rounding up, and the formation of apoptotic bodies, indicating that BK-17 induced apoptosis in the cell lines. Of note, RT-PCR and Western blotting data indicated that the BK-17 treatment induced the down-regulation of antiapoptotic Bcl-2 members, Bcl-2 and $Bcl-X_L$, and the up-regulation of proapoptotic Bax members, Bax and Bad, in the AGS cells. BK-17-induced apoptosis of AGS cells was involved in the proteolytic activation of caspase-3, caspase-8, and caspase-9. Taken together, these findings suggest that BK-17 is associated with the induction of apoptotic cell death.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2019.04a
• /
• pp.111-111
• /
• 2019

Glycyrrhizae radix is one of the most frequently prescribed ingredients in Oriental medicine, and G. radix extract has been shown to exert anti-cancer effects. However, the cellular and molecular mechanisms of apoptosis by G. radix are poorly defined. In the present study, it was examined the biochemical mechanisms of apoptosis by water extract of G. radix (WEGR) in human bladder T24 cancer cells. It was found that WEGR could inhibit the cell growth of T24 cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, DNA fragmentation and increased populations of annexin-V positive cells. The induction of apoptotic cell death by WEGR was connected with an up-regulation of pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL proteins, and inhibition of apoptosis family proteins (XIAP, cIAP-1 and cIAP-2). In addition, apoptosis-inducing concentrations of WEGR induced the activation of caspase-9, an initiator caspase of the mitochondrial-mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. WEGR also induced apoptosis via a death receptor-mediated extrinsic pathway by caspase-8 activation, resulting in the down-regulation of total Bid and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. Taken together, the present results suggest that WEGR may be a potential chemotherapeutic agent for the control of human bladder cancer cells.

• Childhood Kidney Diseases
• /
• v.6 no.1
• /
• pp.75-84
• /
• 2002

Purpose Acute pyelonephritis of growing kidneys may result in renal scarring. TGF-${\beta}1$, inflammatory cytokine, has been suggested to play an important role in promoting renal scarring through apoptosis, suppression of cellular proliferation and fibrosis. We observed the effects of a potent anti-inflammatory agent, methylprednisolone on apoptosis and renal scarring in experimentally induced acute pyelonephritic weaning rats. Materials and Methods: To induce ascending pyelonephritis a saline solution containing Escherichia coli type ATCC No. 25922, pili- form (107 bacteria/mL) was infused into the bladder through the 16-guage silicone cannula for 48 hours to 102 three-week-old Sprague-Dawley rats (50-60g). Experimental groups were divided into three groups according to the treatment protocols, group I (ceftriaxone only, n=3l), group II (methylprednisolone+ceftriaxone n=28), control group (n=43) was not treated. Histopathologic scores of inflammatory changes, fibrosis and tubular atrophy, the apoptosis index and TGF-${\beta}1$ expression score were observed at post-infection 1 and 3 week. Datas were analysed using ANOVA test and P value below 0.05 was interpreted as significant. Results: The mortality rate ($21.4\%$) of group II was not different to the control group ($41.9\%$) and group I ($32.3\%$). The inflammatory score of group II ($0.8{\pm}0.87$) at week 1 was significantly lower than those of the control group ($2.3{\pm}0.87$) and Group I ($1.7{\pm}0.79$) (P<0.05). Apoptosis index of group II ($2.9{\pm}2.15$) at week 1 was significantly lower than those of the control group ($10.0{\pm}1.95$) and group 1 ($8.3{\pm}2.53$) (P<0.05). TCF-${\beta}1$ expression score of group II ($0.8{\pm}0.72$) at week 1 was significantly lower than those of the control group ($1.9{\pm}0.68$) and group I ($1.8{\pm}0.60$) (P<0.05). The fibrosis score of group II ($1.1{\pm}1.10$) at week 3 was significantly lower than that of the group I ($1.8{\pm}0.83$) (P<0.05) Conclusion: Conclusion Combined treatment with methylprednisolone and ceftriaxone reduced inflammation, fibrosis, apoptosis and TGF-${\beta}1$ expression in acute pyelonephritic weaning rats, compared to ceftriaxone alone. Anti-inflammatory agent supplemented to antibiotics could prevent renal scarring more effectively. (J Korean Soc Pediatr Nephrol 2002 ; 6 : 75-84)