1.Fabry disease exacerbates renal interstitial fibrosis after unilateral ureteral obstruction via impaired autophagy and enhanced apoptosis
Sungjin CHUNG ; Mina SON ; Yura CHAE ; Songhee OH ; Eun Sil KOH ; Yong Kyun KIM ; Seok Joon SHIN ; Cheol Whee PARK ; Sung-Chul JUNG ; Ho-Shik KIM
Kidney Research and Clinical Practice 2021;40(2):208-219
Background:
Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear.
Methods:
Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys.
Results:
Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice.
Conclusion
These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.
2.Fabry disease exacerbates renal interstitial fibrosis after unilateral ureteral obstruction via impaired autophagy and enhanced apoptosis
Sungjin CHUNG ; Mina SON ; Yura CHAE ; Songhee OH ; Eun Sil KOH ; Yong Kyun KIM ; Seok Joon SHIN ; Cheol Whee PARK ; Sung-Chul JUNG ; Ho-Shik KIM
Kidney Research and Clinical Practice 2021;40(2):208-219
Background:
Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear.
Methods:
Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys.
Results:
Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice.
Conclusion
These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.
3.Intranasal Vaccination with OuterMembrane Protein of Orientia tsutsugamushi induces Protective Immunity Against Scrub Typhus
Sung-Moo PARK ; Min Jeong GU ; Young-Jun JU ; In Su CHEON ; Kyu-Jam HWANG ; Byoungchul GILL ; Byoung-Shik SHIM ; Hang-Jin JEONG ; Young Min SON ; Sangho CHOI ; Woonhee JEUNG ; Seung Hyun HAN ; Hyuk CHU ; Cheol-Heui YUN
Immune Network 2021;21(2):e14-
Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.
4.Robot-Assisted Laparoscopic Myomectomy versus Abdominal Myomectomy for Large Myomas Sized over 10 cm or Weighing 250 g
Sa Ra LEE ; Eun Sil LEE ; Young-Jae LEE ; Shin-Wha LEE ; Jeong Yeol PARK ; Dae-Yeon KIM ; Sung Hoon KIM ; Yong-Man KIM ; Dae-Shik SUH ; Young-Tak KIM
Yonsei Medical Journal 2020;61(12):1054-1059
Purpose:
Here, we compared the operative and perioperative outcomes between robot-assisted laparoscopic myomectomy (RALM) and abdominal myomectomy (AM) in patients with large (>10 cm) or heavy myomas (>250 g).
Materials and Methods:
We included 278 patients who underwent multi-port RALM (n=126) or AM (n=151) for large or heavy myomas in a tertiary care hospital between April 2019 and June 2020. The t-test, chi-square, Bonferroni’s test, and multiple linear regression were used.
Results:
No differences were observed in age, body mass index, parity, or history of pelvic surgery between the two groups. Myoma diameters were not different (10.8±2.52 cm vs. 11.2±3.0 cm, p=0.233), but myomas were lighter in the RALM group than in the AM group (444.6±283.14 g vs. 604.68±368.35 g, respectively, p=0.001). The RALM group had a higher proportion of subserosal myomas, fewer myomas, fewer large myomas over >3 cm, lighter myomas, and longer total operating time. However, the RALM group also had shorter hospital stay and fewer short-term complications. Estimated blood loss (EBL) was not different between the two groups. The number of removed myomas was the most significant factor (coefficient=10.89, p<0.0001) affecting the EBL.
Conclusion
RALM is a feasible myomectomy technique even for large or heavy myomas. RALM patients tend to have shorter hospital stays and fewer postoperative fevers within 48 hours. However, RALM has longer total operating time.
5.Characteristics of COVID-19 Patients Who Progress to Pneumonia on Follow-Up Chest Radiograph: 236 Patients from a Single Isolated Cohort in Daegu, South Korea
Ha Kyung JUNG ; Jin Young KIM ; Mu Sook LEE ; Ji Yeon LEE ; Jae Seok PARK ; Miri HYUN ; Hyun Ah KIM ; Yong Shik KWON ; Sang-Woong CHOI ; Sung Min MOON ; Young Joo SUH
Korean Journal of Radiology 2020;21(11):1265-1272
Objective:
We investigated the prevalence of pneumonia in novel coronavirus disease 2019 (COVID-19) patients using chest radiographs to identify the characteristics of those with initially negative chest radiographs, who were positive for pneumonia on follow-up.
Materials and Methods:
Retrospective cohort data of 236 COVID-19 patients were reviewed. Chest radiography was performed on admission, with serial radiographs obtained until discharge. The ‘positive conversion group’ was defined as patients whose initial chest radiographs were negative but were positive for pneumonia during follow-up. Patients with initially positive chest radiographs were defined as the ‘initial pneumonia group.’ Patients with negative initial and follow-up chest radiographs were defined as the ‘non-pneumonia group.’ Clinical and laboratory findings were compared between groups, and predictors of positive conversion were investigated.
Results:
Among 236 patients, 108 (45.8%) were in the non-pneumonia group, 69 (29.2%) were in the initial pneumonia group, and 59 (25%) were in the positive conversion group. The patients in the ‘initial pneumonia group’ and ‘positive conversion group’ were older, had higher C-reactive protein (CRP) and lactate dehydrogenase levels, and lower absolute lymphocyte counts than those in the ‘non-pneumonia group’ (all p < 0.001). Among patients with negative initial chest radiographs, age ≥ 45 years (odds ratio [OR]: 3.93, 95% confidence interval [CI]: 1.76–8.75, p = 0.001), absolute lymphocyte count < 1500 cells/µL (OR: 2.25, 95% CI: 1.03–4.89,p = 0.041), and CRP > 0.5 mg/dL (OR: 3.91, 95% CI: 1.54–9.91, p = 0.004) were independent predictors for future development of pneumonia.
Conclusion
More than a half of COVID-19 patients initially had normal chest radiographs; however, elderly patients (≥ 45 years of age) with abnormal laboratory findings (elevated CRP and low absolute lymphocyte counts) developed pneumonia on follow-up radiographs.
6.Analysis of the Time Interval between the Physician Order for Life-Sustaining Treatment Completion and Death
Sung Yoon JOUNG ; Chung-woo LEE ; Youn Seon CHOI ; Seon Mee KIM ; Seok Won PARK ; Eun Shik MO ; Jae Hyun PARK ; Jean SHIN ; Hyun Jin LEE ; Hong Seok PARK
Korean Journal of Family Medicine 2020;41(6):392-397
Background:
This study aimed to explore the time interval distribution pattern between the Physicians Order for Life-Sustaining Treatment (POLST) form completion and death at a tertiary hospital in South Korea. It also examined the association between various independent parameters and POLST form completion timing.
Methods:
A total of 150 critically ill patients admitted to Korea University Guro Hospital between June 1, 2018 and December 31, 2018 who completed the POLST form were retrospectively analyzed and included in this study. Data were analyzed with descriptive statistics, and group comparisons were performed using the chi-square test for categorical variables. Fisher’s exact test was also used to compare cancer versus non-cancer groups.
Results:
More than half the decedents (54.7%) completed their POLST within 15 days of death and 73.4% within 30 days. The non-cancer group had the highest percentage of patients (77.8%) who died within 15 days of POLST form completion while the colorectal (39.1%) and other cancer (37.5%) groups had the lowest (P=0.336).
Conclusion
Our findings demonstrated a current need for more explicit guidance to assist physicians with initiating more timely, proactive end-of-life discussions.
7.The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea
Mi Kyung KIM ; Jae-Han JEON ; Sung-Woo KIM ; Jun Sung MOON ; Nan Hee CHO ; Eugene HAN ; Ji Hong YOU ; Ji Yeon LEE ; Miri HYUN ; Jae Seok PARK ; Yong Shik KWON ; Yeon-Kyung CHOI ; Ki Tae KWON ; Shin Yup LEE ; Eon Ju JEON ; Jin-Woo KIM ; Hyo-Lim HONG ; Hyun Hee KWON ; Chi Young JUNG ; Yin Young LEE ; Eunyeoung HA ; Seung Min CHUNG ; Jian HUR ; June Hong AHN ; Na-young KIM ; Shin-Woo KIM ; Hyun Ha CHANG ; Yong Hoon LEE ; Jaehee LEE ; Keun-Gyu PARK ; Hyun Ah KIM ; Ji-Hyun LEE
Diabetes & Metabolism Journal 2020;44(4):602-613
Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. Compared with the non-DM group ( DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.
8.Catheter-Related Bladder Discomfort: How Can We Manage It?
Eun Bi JANG ; Seong Hwi HONG ; Kyu Shik KIM ; Sung Yul PARK ; Yong Tae KIM ; Young Eun YOON ; Hong Sang MOON
International Neurourology Journal 2020;24(4):324-331
The urethral catheter is used in various clinical situations such as diagnosing urologic disease, urine drainage in patients after surgery, and for patients who cannot urinate voluntarily. However, catheters can cause numerous adverse effects, such as catheter-associated infection, obstruction, bladder stones, urethral injury, and catheter-related bladder discomfort (CRBD). CRBD symptoms vary among patients from burning sensation and pain in the suprapubic and penile areas to urinary urgency. CRBD significantly reduces patient quality of life and can lead to several complications. CRBD is caused by catheter-induced bladder irritation due to muscarinic receptor-mediated involuntary contractions of bladder smooth muscle and also can be caused by mechanical stimulus of the urethral catheter. Various pharmacologic studies for managing CRBD, including antimuscarinic and antiepileptic agents and botulinum toxin injections have been reported. If urologists can reduce patients’ CRBD, their quality of life and recovery can improve.
9.Depression as a Mediator of Chronic Fatigue and Post-Traumatic Stress Symptoms in Middle East Respiratory Syndrome Survivors
So Hee LEE ; Hyoung Shik SHIN ; Hye Yoon PARK ; Jeong Lan KIM ; Jung Jae LEE ; Haewoo LEE ; Sung Doo WON ; Woori HAN
Psychiatry Investigation 2019;16(1):59-64
OBJECTIVE: The relationship among chronic fatigue, depressive symptoms, and post-traumatic stress symptoms (PTSSs) among Middle East respiratory syndrome (MERS) survivors is poorly understood. METHODS: Of 148 survivors who consented to be registered and underwent assessments at 12 months (T1) and 18 months (T2) after the MERS outbreak, 72 (48.65%) were evaluated for chronic fatigue, depressive symptoms, and PTSSs based on the Impact of Event ScaleRevised (IES-R), the Patient Health Questionnaire-9 (PHQ-9), and the Fatigue Severity Scale (FSS). Data from 52 subjects, who completed both assessments, were analyzed using a regression-based serial multiple mediation model (PROCESS Model 6). RESULTS: Bootstrap analyses indicated no direct effects of T1 FSS on T2 IES-R but significant positive indirect effects of T1 FSS on T2 IESR through T1 PHQ-9 and T2 PHQ-9 (B=2.1601, SE=1.3268, 95% confidence interval=0.4250–6.1307). In other words, both T1 PHQ-9 and T2 PHQ-9 fully mediated the relationship between T1 FSS and T2 IES. CONCLUSION: Chronic fatigue 12 months after MERS had indirect effects on prolonged PTSSs 18 months after MERS via persisting depression in MERS survivors. This finding supports the need to promote interventional programs for emerging infectious disease survivors with chronic fatigue to reduce depression and prevent prolonged PTSSs.
Communicable Diseases, Emerging
;
Coronavirus Infections
;
Depression
;
Fatigue
;
Humans
;
Middle East
;
Negotiating
;
Survivors
10.Comparison of Seropositivity to Trichomonas vaginalis between Men with Prostatic Tumor and Normal Men
Jung Hyun KIM ; Hong Sang MOON ; Kyu Shik KIM ; Hwan Sik HWANG ; Jae Sook RYU ; Sung Yul PARK
The Korean Journal of Parasitology 2019;57(1):21-25
Trichomoniasis is the most common curable sexually-transmitted infection. Most Trichomonas vaginalis-infected men are asymptomatic and can remain undiagnosed and untreated, and this has been thought to result in chronic persistent prostatic infection. Chronic inflammation is regarded as the major factor in the pathogenesis and progression of benign prostatic hyperplasia (BPH) and prostatic cancer (PCa). The aim of this study is to identify seropositivity to T. vaginalis in men with prostate tumors (BPH or PCa) visited to Hanyang University Hospital. A total of 183 men were enrolled between October 2013 and November 2014. They consisted of 139 with BPH (mean age: 64.0±0.07) and 44 with prostate cancer (mean age: 73.3±0.18). We carried out ELISA to identify the seropositivity to T. vaginalis. Mixed lysate antigen extracted from 8 strains of T. vaginalis was used in the ELISA. Also 58 male outpatients visited to Health Promotion Center in Hanyang University Hospital were evaluated for comparing group. As a results, seropositivity to T. vaginalis in patients with prostatic diseases was 19.7% (BPH: 18.7%, PCa: 22.7%) and it was significantly higher than the 1.7% of the comparing healthy group (P=0.001). Therefore, prostatic tumor showed higher seropositivity against T. vaginalis than normal men. As far as we know, this is the first report about seroprevalence in prostatic tumor in Korea.
Enzyme-Linked Immunosorbent Assay
;
Health Promotion
;
Humans
;
Inflammation
;
Korea
;
Male
;
Outpatients
;
Passive Cutaneous Anaphylaxis
;
Prostate
;
Prostatic Diseases
;
Prostatic Hyperplasia
;
Prostatic Neoplasms
;
Seroepidemiologic Studies
;
Trichomonas vaginalis
;
Trichomonas

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