Post-partum myocardial ischemia due to intramuscular methylergonovine-induced coronary vasospasm: case report.

BACKGROUND: Methylergonovine is a vasoconstrictive agent historically used as a provocative agent in the lab for coronary vasospasm; it is also a first line uterotonic agent for management of postpartum hemorrhage. CASE PRESENTATION: A 29-year-old female with history of smoking and idiopathic thrombocytopenia received intramuscular methylergonovine after delivery of twins for intrauterine hemorrhage management. Subsequently, she had episodes of chest pain with high sensitivity Troponin I elevation to 1509 ng/L with accompanying septal T wave inversions, decreased left ventricular ejection fraction to 49% and basal septal wall hypokinesis. Computed tomography (CT) coronary angiogram showed patent coronary arteries and no coronary arterial dissection. The patient was conservatively managed with aspirin and metoprolol, and on follow up had fully recovered left ventricular function with resolution of wall motion abnormalities. Given this, coronary vasospasm due to intramuscular methylergonovine is the most likely cause of patient's chest pain and associated myocardial ischemia. CONCLUSIONS: Intramuscular, intrauterine, intravenous, and even oral methylergonovine can rarely cause coronary vasospasm leading to myocardial ischemia. Cardiologists caring for postpartum patients should be aware of these potential lethal complications; prompt identification and administration of sublingual nitroglycerin can prevent severe complications of arrythmias, heart block, or cardiac arrest.

Induced Pluripotent Stem Cell-Derived Endothelial Cells: Overview, Current Advances, Applications, and Future Directions.

Endothelial cells are prevalent in our bodies and serve multiple functions. By lining the vasculature, they provide a barrier to tissues and facilitate the transport of molecules and cells. They also maintain hemostasis and modulate blood flow by reacting to chemokines and releasing signal molecules. Thus, endothelial dysfunction leads to a wide variety of diseases, including atherosclerosis and coronary artery disease. In today's era of stem cell research, induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) have emerged for research and engineering purposes. They are not only tools for studying disease states but are also a crucial part of efforts to engineer vessel and organ grafts. As the techniques in cell culture, microfluidics, and personalized medicine concomitantly improve, the potential for iPSC-ECs is enormous. We review functions of endothelium in our bodies, the development and uses of iPSC-ECs, and the possible avenues to explore in the future.

Clinical assessment of bipolar depression: validity, factor structure and psychometric properties of the Korean version of the Bipolar Depression Rating Scale (BDRS).

BACKGROUND: The Bipolar Depression Rating Scale (BDRS) is a scale for assessment of the clinical characteristics of bipolar depression. The primary aims of this study were to describe the development of the Korean version of the BDRS (K-BDRS) and to establish more firmly its psychometric properties in terms of reliability and validity. METHODS: The study included 141 patients (62 male and 79 female) who had been diagnosed with bipolar disorder, were currently experiencing symptoms of depression, and were interviewed using the K-BDRS. Other measures included the Montgomery and Asberg Depression Scale (MADRS), the 17-item Hamilton Depression Scale (HAMD), and the Young Mania Rating Scale (YMRS). Additionally, the internal consistency, concurrent validity, inter-rater reliability, and test-retest reliability of the K-BDRS were evaluated. RESULTS: The Cronbach's α-coefficient for the K-BDRS was 0.866, the K-BDRS exhibited strong correlations with the HAMD (r = 0.788) and MADRS (r = 0.877), and the mixed symptoms score of the K-BDRS was significantly correlated with the YMRS (r = 0.611). An exploratory factor analysis revealed three factors that corresponded to psychological depressive symptoms, somatic depressive symptoms, and mixed symptoms. CONCLUSIONS: The present findings suggest that the K-BDRS has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in patients with bipolar disorder.

Psychometric Properties of the Korean Version of Functioning Assessment Short Test in Bipolar Disorder.

Objective: The Functioning Assessment Short Test (FAST) is a relatively specific test for bipolar disorders designed to assess the main functioning problems experienced by patients. This brief instrument includes 24 items assessing impairment or disability in 6 domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. It has already been translated into standardized versions in several languages. The aim of this study is to measure the validity and reliability of the Korean version of FAST (K-FAST). Methods: A total of 209 bipolar disorder patients were recruited from 14 centers in Korea. K-FAST, Young Mania Rating Scale (YMRS), Bipolar Depression Rating Scale (BDRS), Global Assessment of Functioning (GAF) and the World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF) were administered, and psychometric analysis of the K-FAST was conducted. Results: The internal consistency (Cronbach's alpha) of the K-FAST was 0.95. Test-retest reliability analysis showed a strong correlation between the two measures assessed at a 1-week interval (ICC = 0.97; p < 0.001). The K-FAST exhibited significant correlations with GAF (r = -0.771), WHOQOL-BREF (r = -0.326), YMRS (r = 0.509) and BDRS (r = 0.598). A strong negative correlation with GAF pointed to a reasonable degree of concurrent validity. Although the exploratory factor analysis showed four factors, the confirmatory factor analysis of questionnaires had a good fit for a six factors model (CFI = 0.925; TLI = 0.912; RMSEA = 0.078). Conclusion: The K-FAST has good psychometric properties, good internal consistency, and can be applicable and acceptable to the Korean context.

Effect of relative handgrip strength on cardiovascular disease among Korean adults aged 45 years and older: Results from the Korean Longitudinal Study of Aging (2006-2016).

BACKGROUND: Aging causes both structural and functional changes in the skeletal muscle, and is associated with changes in body composition form, which results in an increased incidence of cardiovascular death. Handgrip strength (HGS) is a simple, fast, reliable, and cost-effective tool for measuring muscle strength. OBJECTIVE: We aimed to investigate which index was most suitable for predicting cardiovascular disease (CVD), and suggested the optimal cut-off points based on the handgrip strength index. In addition, we aimed to identify the effects of weak HGS, as determined by applying the optimal cut point on the occurrence of CVD. METHOD: A total of 8494 older men and women aged over 45 years from the Korean Longitudinal Study of Aging (KLoSA) were included in this study at baseline. We performed general estimating equations (GEE) with independent correlation structure to assess whether handgrip strength is longitudinally related to occurrence of CVDs such as heart disease or stroke reported from 1 st to 6th wave of KLoSA. RESULTS: The relative HGS was strongly associated with CVD in both sexes, and the best fit model was in that in comparison to dominant HGS and absolute HGS. In addition, we calculated the optimal cut point for CVD based on the relative HGS in this study (men: 2.52 and women: 1.55, respectively), and demonstrated that low HGS, as determined by applying relative HGS cut points, was associated with a higher OR for CVD compared to normal HGS; the associations observed were consistent between the sexes. CONCLUSIONS: Our findings suggest that HGS has the potential to be a valuable screening tool for cardiovascular risk in clinical settings; this is advantageous in situations where blood sampling is not possible since HGS is easily measured and highly reproducible. It is necessary to pay attention to weak grip strength against body size in the elderly population.

Association between Hand Grip Strength and Self-Rated Health in Middle- and Old-Aged Korean Citizens.

BACKGROUND: To investigate the relationship between hand grip strength (HGS) and self-rated health in middleand old-aged Korean subjects. METHODS: The data used for this study were derived from the Korean Longitudinal Study of Aging. A total of 9,132 participants were enrolled using the year 2006 as the baseline, with additional data collected throughout the followup period until 2016. Chi-square test and generalized estimating equation regression models were used for data analysis. HGS was measured in a sitting position with the elbow fixed at 90° on both sides using a dynamometer, and calculated using the values measured from both sides. Relative HGS was measured by dividing HGS by the subject's body mass index. Self-rated health was assessed with the question "How would you rate your current health in general?" and answers were categorized as "excellent," "moderate," or "poor." RESULTS: HGS was shown to be inversely associated with self-rated health (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.93-0.94; P<0.0001). Patients aged 65 years or older with lower scores were more likely to report poor self-rated health. Similar results were obtained with relative HGS (OR, 0.40; 95% CI, 0.36-0.45; P<0.0001), but standard HGS had better model fitting (quasi-likelihood under independence model criteria=33,890). CONCLUSION: HGS may be considered an index for the diagnosis of sarcopenia and may also affect self-rated health, which is a multidimensional indicator of an individual's health status and can identify patients who may require special attention.

Developing a mobile epilepsy management application integrated with an electronic health record for effective seizure management.

INTRODUCTION: Epilepsy is a chronic neurological disorder characterized by recurrent spontaneous seizures. Over 70% epilepsy patients can live normally if their seizures can be controlled. For this, many factors should be tracked and managed, but doing so is hard because of individual differences. There are mobile applications to help track these factors; however, no application covers crucial factors comprehensively, and they are complicated to use. Therefore, this study aimed to develop a mobile epilepsy management application covering crucial factors comprehensively in a user-friendly way. We evaluated the pilot version with a usability and satisfaction survey and an interview. METHODS: We established a task force comprising professionals from various fields who participated in all processes of this research. Existing service analysis and professional interviews were conducted to draw a function list. User interface and graphic user interface were designed under the supervision of the task force. After developing the application's pilot version, usability and satisfaction of the application were evaluated with eight patients and caregivers through scenario-based usability test, satisfaction survey, and interview. RESULTS: All existing mobile epilepsy management applications provide seizure and medication diary functions. We decided to provide six main functions: seizure diary, medication reminder, appointments, outpatient survey, education materials, and personal dashboard (My epilepsy). We also integrated the application with the hospital's electronic health record system. To simplify usability, frequently used and relatively important functions are located in the main page as "seizure recording" and "medication diary." Additionally, when designing graphics, art therapy was used to enhance psychological stability. For evaluation, eight participants were recruited. In scenario-based tasks, among 10 tasks, all participants completed six tasks. However, only 37.5% participants could record seizures in detail. System Usability Scale score was 84.5 points, indicating that the system was satisfactory. CONCLUSION: This study confirmed that patients' satisfaction of this application were high. Additionally, it helped them record their seizures accurately, which is very useful for seizure trend analysis, discovering seizure trigger factors, and ensuring efficient management of epilepsy. Through integration with the electronic health record, patient medical information could be utilized to guide physicians' decision-making for setting future medical treatment plan and could contribute greatly to the overall management of epilepsy.

Development of Health-RESPECT: An Integrated Service Model for Older Long-Term Care Hospital/Nursing Home Patients Using Information and Communication Technology.

BACKGROUND: Korea, as one of the fastest-aging countries worldwide, requires an improved healthcare service model for older adults. We evaluated the current healthcare system and developed a service model based on information and communication technologies (ICT) for use in older patients in long-term care facilities (LTCF). METHODS: We conducted a qualitative literature review, focus group interviews (FGIs), and structured survey to identify the current technology use and status of healthcare systems. We then developed a web-based platform with necessary, high-priority, and usable content for the care of older patients in LTCF. RESULTS: We reviewed 60 (23 hypertension, 18 diabetes, and 19 heart failure) articles on information and communication technologies (ICT)-based disease management for clinical effectiveness and improved patient satisfaction. FGIs and structured surveys were used to evaluate the inconvenience in patient and medical information transfer between hospitals and cost and time required for its process. Accordingly, we confirmed the unmet need for an ICT-based service model for management, monitoring, and consultation among older patients and developed the Health-RESPECT (integrated caRE Systems for elderly PatiEnts using iCT), a service platform for older patients residing in LTCF. The medical information exchange system was used to transfer medical information. Health-RESPECT includes an established algorithm for evidence-based comprehensive geriatric assessment and customized management; chronic disease management; management of potentially inappropriate medications; rehabilitation; and consultation and videoconferencing. CONCLUSION: This study identified the current status and unmet needs of healthcare systems for older adults. We developed an ICT-based system to manage older institutionalized patients. However, the Health-RESPECT service model requires further validation.

Factors Influencing Acceptance of Personal Health Record Apps for Workplace Health Promotion: Cross-Sectional Questionnaire Study.

BACKGROUND: Health care technologies can help improve workers' health and productivity by supporting workplace health promotion. A personal health record app is used to manage medical data such as results from medical checkups, which facilitates decision making for medical personnel. However, an analysis of users' technology acceptance is required to provide appropriate services based on personal health record apps. OBJECTIVE: The purpose of this study was to analyze the factors influencing the behavioral intention of health experts and workers to use an app in workers' health centers and to examine differences in their perception of the main variables. METHODS: The study involved health experts and workers who visited 21 workers' health centers in Korea to verify a research model in which perceived risk was added to the unified theory of acceptance and use of technology, a representative theory of information technology acceptance. After receiving ethical approval from the Korea National Institute for Bioethics Policy, 1050 questionnaires were distributed over 7 weeks with cooperation of the Korea Occupational Safety and Health Agency. A multiple linear regression analysis and multigroup path analysis were performed to verify the hypotheses, and independent samples t tests were performed to analyze differences between workers' and health experts' perception of the main variables. RESULTS: The analysis included data from 866 respondents (687 workers and 179 health experts). Effort expectancy (beta=.08, P=.03), social influence (beta=.43, P<.001), performance expectancy (beta=.07, P=.008), and facilitating conditions (beta=.13, P<.001) exerted significant positive effects on behavioral intention, whereas perceived risk (beta=-.29, P<.001) exerted a significant negative effect on behavioral intention. Performance expectancy had a significant effect on path differences depending on gender (critical ratio=-3.38) and age (critical ratio=1.97). Workers' mean scores for the main variables were higher relative to those of health experts for all remaining variables except perceived risk, and significant differences were observed for all remaining variables except facilitating condition. CONCLUSIONS: Social influence exerted the strongest effect on behavioral intention to use the personal health record app. Consequently, it is necessary to coordinate health promotion activities in the workplace as well as the operational direction of community institutions such as in workers' health centers to allow workers to manage their own health via continuous use of the app. In addition, the app should be developed based on a requirement analysis of the balance between both interest groups in consideration of differences in perspective between consumers and service providers.

Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells.

The availability of an autologous transplantable auxiliary liver would dramatically affect the treatment of liver disease. Assembly and function in vivo of a bioengineered human liver derived from induced pluripotent stem cells (iPSCs) has not been previously described. By improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, we generated functional engineered human mini livers and performed transplantation in a rat model. Whereas previous studies recellularized liver scaffolds largely with rodent hepatocytes, we repopulated not only the parenchyma with human iPSC-hepatocytes but also the vascular system with human iPS-endothelial cells, and the bile duct network with human iPSC-biliary epithelial cells. The regenerated human iPSC-derived mini liver containing multiple cell types was tested in vivo and remained functional for 4 days after auxiliary liver transplantation in immunocompromised, engineered (IL2rg-/-) rats.

Validation of the Korean Version of the Depression in Old Age Scale and Comparison with Other Depression Screening Questionnaires Used in Elderly Patients in Medical Settings.

OBJECTIVE: The Depression in Old Age Scale (DIA-S) is a new screening tool for assessing depression in the elderly. The primary aims of this study were to describe the validation of the Korean version of the DIA-S (K-DIA-S) and to compare its validity with that of other depression screening questionnaires used in elderly outpatients in medical settings. METHODS: A total of 385 elderly outpatients completed the K-DIA-S and underwent the Mini International Neuropsychiatric Interview to diagnose depressive disorders. Other measures included the 15-item short form of the Geriatric Depression Scale (SGDS), the 9-item depression module of the Patient Health Questionnaire (PHQ-9), and the Montgomery-Asberg Depression Rating Scale (MADRS). Reliability and validity tests, an optimal cutoff point estimate, and receiver operating characteristic curve analysis were performed to investigate the diagnostic validity of the K-DIA-S. Areas under the curves (AUCs) for the K-DIA-S, SGDS, and PHQ-9 were compared statistically. RESULTS: The K-DIA-S showed good internal consistency and strong correlations with the SGDS (r = 0.853), PHQ-9 (r= 0.739), and MADRS (r= 0.772). The cut-off point of the K-DIA-S that can be recommended for screening depressive symptoms was a score of 4. For "any depressive disorder", the AUC (standard error) for the K-DIA-S was 0.896 (0.015), which was significantly larger than that for the PHQ-9 (p= 0.033). CONCLUSION: The present findings suggest that the K-DIA-S has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in elderly populations and medically ill patients.

Switching Antipsychotics to Blonanserin in Patients with Schizophrenia: An Open-label, Prospective, Multicenter Study.

OBJECTIVE: This study was performed to investigate the efficacy and tolerability of blonanserin in schizophrenic patients who were previously treated with other antipsychotics but, due to insufficient response, were switched to blonanserin. METHODS: A total of 52 patients with schizophrenia who were unresponsive to treatment with antipsychotic monotherapy or combination therapy were recruited into this 12-week, open-label, prospective, multicenter study. Patients were switched to blonanserin from their existing antipsychotics over a maximum 2-week tapering-off period. Efficacy was primarily evaluated using the 18-item Brief Psychiatric Rating Scale (BPRS). Assessments were performed at baseline, and at weeks 1, 2, 4, 8, and 12. RESULTS: Switching to blonanserin resulted in a significant decrease in the mean total score on the BPRS from baseline (56.8 ± 9.4) to week 12 (42.1 ± 13.8, p > 0.001). The most common adverse events were extrapyramidal symptoms (n = 12, 23.1%), insomnia (n = 10, 19.2%), and emotional arousal (n = 6, 11.5%). Overweight or obese patients (body mass index ≥ 23 kg/m2, n = 33) who switched to blonanserin exhibited significant weight loss from 75.2 ± 9.3 kg at baseline to 73.5 ± 9.2 kg at week 12 (p = 0.006). The total cholesterol (baseline, 236.1 ± 47.6 mg/dl; endpoint [week 12], 209.9 ± 28.0 mg/dl; p = 0.005) and prolactin levels (baseline, 80.0 ± 85.2 ng/ml; endpoint [week 12], 63.2 ± 88.9 ng/ml; p = 0.003) were also significantly improved in patients with hypercholesterolemia or hyperprolactinemia. CONCLUSION: The results of the present study suggest that switching to blonanserin may be an effective strategy for schizophrenic patients unresponsive to other antipsychotic treatments.

Screening with the Korean Version of the Mood Disorder Questionnaire for Bipolar Disorders in Adolescents: Korean Validity and Reliability Study.

OBJECTIVE: This study aimed to evaluate the validity and reliability of a Korean version of the Mood Disorder Questionnaire-Adolescent version (K-MDQ-A) as a screening instrument for bipolar disorders in adolescents. METHODS: One hundred two adolescents with bipolar disorders and their parents were recruited from November 2014 to November 2016 at 7 training hospitals. One hundred six controls were recruited from each middle school in two cities of South Korea. The parent version of the original MDQ-A was translated into Korean. The parents of all participants completed the K-MDQ-A. The diagnoses of bipolar disorders were determined based on the Korean version of K-SADS-PL. The test-retest reliability with a 10-month interval was investigated in 33 bipolar adolescents. RESULTS: K-MDQ-A yielded a sensitivity of 0.90 and a specificity of 0.92 when using a cut-off score of endorsement of 5 items, indicating that symptoms occurred in the same time period and caused moderate or serious problems. The internal consistency of the K-MDQ-A was good. The correlations between each item and the total score ranged from 0.40 to 0.76 and were all statistically significant. Factor analysis revealed 3 factors that explained 61.25% of the total variance. The mean total score was significantly higher in bipolar adolescents (7.29) than in controls (1.32). The Pearson correlation coefficient for the total test-retest score was 0.59 (p＜0.001). CONCLUSION: The K-MDQ-A completed by parents showed the excellent validity and reliability and may be a useful screening tool for adolescents with bipolar disorders attending in- and outpatient psychiatric clinics.

Biomechanical and Hemodynamic Measures of Right Ventricular Diastolic Function: Translating Tissue Biomechanics to Clinical Relevance.

BACKGROUND: Right ventricular (RV) diastolic function has been associated with outcomes for patients with pulmonary hypertension; however, the relationship between biomechanics and hemodynamics in the right ventricle has not been studied. METHODS AND RESULTS: Rat models of RV pressure overload were obtained via pulmonary artery banding (PAB; control, n=7; PAB, n=5). At 3 weeks after banding, RV hemodynamics were measured using a conductance catheter. Biaxial mechanical properties of the RV free wall myocardium were obtained to extrapolate longitudinal and circumferential elastic modulus in low and high strain regions (E1 and E2, respectively). Hemodynamic analysis revealed significantly increased end-diastolic elastance (Eed) in PAB (control: 55.1 mm Hg/mL [interquartile range: 44.7-85.4 mm Hg/mL]; PAB: 146.6 mm Hg/mL [interquartile range: 105.8-155.0 mm Hg/mL]; P=0.010). Longitudinal E1 was increased in PAB (control: 7.2 kPa [interquartile range: 6.7-18.1 kPa]; PAB: 34.2 kPa [interquartile range: 18.1-44.6 kPa]; P=0.018), whereas there were no significant changes in longitudinal E2 or circumferential E1 and E2. Last, wall stress was calculated from hemodynamic data by modeling the right ventricle as a sphere: stress=Pressure×radius2×thickness. CONCLUSIONS: RV pressure overload in PAB rats resulted in an increase in diastolic myocardial stiffness reflected both hemodynamically, by an increase in Eed, and biomechanically, by an increase in longitudinal E1. Modest increases in tissue biomechanical stiffness are associated with large increases in Eed. Hemodynamic measurements of RV diastolic function can be used to predict biomechanical changes in the myocardium.

Times to Discontinue Antidepressants Over 6 Months in Patients with Major Depressive Disorder.

OBJECTIVE: The aim of the present study was to investigate differences in discontinuation time among antidepressants and total antidepressant discontinuation rate of patients with depression over a 6 month period in a naturalistic treatment setting. METHODS: We reviewed the medical records of 900 patients with major depressive disorder who were initially prescribed only one kind of antidepressant. The prescribed antidepressants and the reasons for discontinuation were surveyed at baseline and every 4 weeks during the 24 week study. We investigated the discontinuation rate and the mean time to discontinuation among six antidepressants groups. RESULTS: Mean and median overall discontinuation times were 13.8 and 12 weeks, respectively. Sertraline and escitalopram had longer discontinuation times than that of fluoxetine, and patients who used sertraline discontinued use significantly later than those taking mirtazapine. No differences in discontinuation rate were observed after 24 weeks among these antidepressants. About 73% of patients discontinued antidepressant treatment after 24 weeks. CONCLUSION: Sertraline and escitalopram tended to have longer mean times to discontinuation, although no difference in discontinuation rate was detected between antidepressants after 24 weeks. About three-quarters of patients discontinued antidepressant maintenance therapy after 24 weeks.

TAK1 mediates lipopolysaccharide-induced RANTES promoter activation in BV-2 microglial cells.

Lipopolysaccharide (LPS), a part of the outer membrane of gram-negative bacteria activates the expression of the regulated upon activation, normal T cell expressed and secreted (RANTES), which plays an important role in the chemo-attraction of leukocytes during the inflammatory response. Recently, we found that LPS-induced RANTES production is mediated by the activation of NF-kappaB, but, the upstream regulatory mechanism involved in mediating this NF-kappaB activation was unclear. In this study, we investigated signal transducing molecules that mediate LPS-induced RANTES promoter activation and found the followings. First, LPS activates the RANTES gene promoter through NF-kappaB binding sites. Second, the expression of dominant negative mutants of TGF-beta-activated kinasel (TAK1) and NF-kappaB-inducing kinase (NIK), blocked the LPS-induced transcriptional activation of RANTES promoter. Moreover, the overexpression of TAK1 along with TAK1-binding protein 1 (TAB1), or NIK stimulated the transcriptional activation of RANTES in the absence of external stimuli. Third, we showed that endogenous TAK1 is phosphorylated by LPS stimulation, and that the association between TAK1 and tumour necrosis factor receptor-associated factor 6 (TRAF6) is constitutive and not induced by LPS treatment. These results indicate that NF-kappaB mediates LPS-triggered RANTES induction and that TAK1 as well as NIK, as NF-kappaB activators participates in LPS-triggered RANTES induction.

Different sensitivity to nephrotoxic agents and osmotic stress in proximal tubular and collecting duct cell lines derived from transgenic mice.

We established six renal tubular cell lines from definite tubular areas of the kidney of transgenic mice harboring tsSV40 large T-antigen gene. Three are proximal tubular cell lines prepared from the S(1), S(2) and S(3) segments of the proximal tubule and the others are collecting duct cell lines obtained from cortical, outer medullary and inner medullary collecting ducts (CCD, OMCD and IMCD, respectively). To verify the growth properties of these cell lines under different temperature conditions (33 and 39 degrees C), two representative cells were chosen from the proximal tubule (S(1) cells) and from the collecting duct (IMCD cells). From these cells, a daily change in cell number was evaluated as a parameter of cell growth. As might be expected, cell numbers of these cells increased only at 33 degrees C. Similar patterns were also observed with the other cell lines. To observe the different sensitivity to nephrotoxic agents in proximal tubular cell lines, the cells were exposed to nephrotoxic agent, gentamicin, ochratoxin A or cisplatin. Gentamicin (1 mg/ml) dose-dependently decreased cellular ATP levels of the S(1) cells only. In contrast, the effect of ochratoxin A (10(-6) M) was most pronounced in the S(2) cells, and that of cisplatin (10 microg/ml) in the S(3) cells. To characterize collecting duct cell lines, a hyperosmotic challenge of 700 or 1100 mOsm/l was applied to the cells. At an isoosmotic condition of 300 mOsm/l, the number of cells from the collecting ducts, regardless of their origin, increased continuously during the culture period of 4 days. At an osmotic concentration of 700 mOsm/l, the number of CCD cells decreased, while OMCD cells showed a gradual but a significant increase in cell numbers throughout the culture period. IMCD cells, however, proliferated even at a concentration as high as 1100 mOsm/l, although an initial decrease in cell number was noted on the first day of culture. For confirmation of intracellular free calcium ([Ca(2+)](i)) mobilization, cells were treated with ATP and bradykinin. The [Ca(2+)](i) was increased significantly and immediately by ATP (10(-4) M) in S(1) cells and bradykinin (10(-7) M) in IMCD cells. From the results obtained, it is indicated that renal tubular cell lines from transgenic mice have different sensitivities to nephrotoxic or osmotic stress showing the conservation of the functional characters of the definite part it originated from.