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Plastic cannulae have attracted increasing interest as an alternative to traditional metal needles with the aim of reducing cannulation-related complications. We investigated whether the substitution volumes during hemodiafiltration differ using these two types of needles in dialysis patients. Methods: An intervention study involving 26 hemodialysis patients was conducted in Korea between March and September in 2021. Patients first received online hemodiafiltration using traditional metal needles, and thereafter plastic cannulae were used in a stepwise protocol. Repeated-measures design and linear mixed-effect models were used to compare substitution volumes between the two needle types with the same inner diameter. Results: The mean patient age was 62.7 years, and their mean dialysis vintage was 95.2 months. Most patients (92.3%) had an arteriovenous fistula as the vascular access. The substitution volume increased as blood flow and needle size increased for both plastic cannulae and metal needles. The substitution volume was significantly higher with 17-gauge (G) plastic cannulae than with 16-G metal needles at blood flow rates of 280, 300, and 330 mL/min. Similar results were obtained for 15-G metal needles and 16-G plastic cannulae at a blood flow rate of 330 mL/min. However, the patient ratings of pain on a visual analogue scale were higher for plastic cannulae. Conclusion: Higher substitution volumes were obtained at the same prescribed blood flow rate with plastic cannulae than with metal needles during online hemodiafiltration. Plastic cannulae are an option for achieving high-volume hemodiafiltration for patients with low blood flow rates.
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Diabetic nephropathy (DN) can affect quality of life (QoL) because it requires arduous lifelong management. This study analyzed QoL differences between DN patients and patients with other chronic kidney diseases (CKDs). Methods: The analysis included subjects (n = 1,766) from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort who completed the Kidney Disease Quality of Life Short Form questionnaire. After implementing propensity score matching (PSM) using factors that affect the QoL of DN patients, QoL differences between DN and non-DN participants were examined. Results: Among all DN patients (n = 390), higher QoL scores were found for taller subjects, and lower scores were found for those who were unemployed or unmarried, received Medical Aid, had lower economic status, had higher platelet counts or alkaline phosphatase levels, or used clopidogrel or insulin. After PSM, the 239 matched DN subjects reported significantly lower patient satisfaction (59.9 vs. 64.5, p = 0.02) and general health (35.3 vs. 39.1, p = 0.04) than the 239 non-DN subjects. Scores decreased in both groups during the 5-year follow-up, and the scores in the work status, sexual function, and role-physical domains were lower among DN patients than non-DN patients, though those differences were not statistically significant. Conclusion: Socioeconomic factors of DN were strong risk factors for impaired QoL, as were high platelet, alkaline phosphatase, and clopidogrel and insulin use. Clinicians should keep in mind that the QoL of DN patients might decrease in some domains compared with non-DN CKDs.
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Since its debut in the biomedical research fields in 1981, zebrafish have been used as a vertebrate model organism in more than 40,000 biomedical research studies. Especially useful are zebrafish lines expressing fluorescent proteins in a molecule, intracellular organelle, cell or tissue specific manner because they allow the visualization and tracking of molecules, intracellular organelles, cells or tissues of interest in real time and in vivo. In this review, we summarize representative transgenic fluorescent zebrafish lines that have revolutionized biomedical research on signal transduction, the craniofacial skeletal system, the hematopoietic system, the nervous system, the urogenital system, the digestive system and intracellular organelles.
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Since its debut in the biomedical research fields in 1981, zebrafish have been used as a vertebrate model organism in more than 40,000 biomedical research studies. Especially useful are zebrafish lines expressing fluorescent proteins in a molecule, intracellular organelle, cell or tissue specific manner because they allow the visualization and tracking of molecules, intracellular organelles, cells or tissues of interest in real time and in vivo. In this review, we summarize representative transgenic fluorescent zebrafish lines that have revolutionized biomedical research on signal transduction, the craniofacial skeletal system, the hematopoietic system, the nervous system, the urogenital system, the digestive system and intracellular organelles.
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Purpose@#The purpose of this study was to investigate the role of carcinoembryonic antigen (CEA) levelsin improving the performance of magnetic resonance imaging (MRI) for the predictionof pathologic response after the neoadjuvant chemoradiation (NCRT) for patients with rectalcancer. @*Materials and Methods@#We retrospectively reviewed the medical records of 524 rectal cancer patients who underwentNCRT and total mesorectal excision between January 2009 and December 2014. Theperformances of MRI with or without CEA parameters (initial CEA and CEA dynamics) forprediction of pathologic tumor response grade (pTRG) were compared by receiver-operatingcharacteristic analysis with DeLong’s method. Cox regression was used to identify the independentfactors associated to pTRG and disease-free survival (DFS) after NCRT. @*Results@#The median follow-up was 64.0 months (range, 3.0 to 113.0 months). On multivariate analysis,poor tumor regression grade on MRI (mrTRG; p < 0.001), initial CEA (p < 0.001) andthe mesorectal fascia involvement on MRI before NCRT (mrMFI; p=0.054) showed associationwith poor pTRG. The mrTRG plus CEA parameters showed significantly improved performancesin the prediction of pTRG than mrTRG alone. All of mrTRG, mrMFI, and initial CEAwere also identified as independent factors associated with DFS. The initial CEA further discriminatedDFS in the subgroups with good mrTRG or that without mrMFI. @*Conclusion@#The CEA parameters significantly improved the performance of MRI in the prediction ofpTRG after NCRT for patients with rectal cancer. The DFS was further discriminated by initialCEA level in the groups with favorable MRI parameters.
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Encapsulating peritoneal sclerosis (EPS) is a potentially fatal complication after long-term peritoneal dialysis, and tamoxifen can be used for its prevention and treatment. However, tamoxifen is known to increase the risk of venous thromboembolism. A 49-year-old woman was admitted with sudden abdominal pain. The patient had received peritoneal dialysis for 20 years and switched to hemodialysis after the diagnosis of EPS. Tamoxifen (10 mg) and prednisolone (20 mg) had been administered for 8 months. On computed tomography, the left hepatic lobe was hardly illuminated, leading to a diagnosis of liver infarction. A month later, she was re-admitted due to abdominal pain and extensive deep vein thrombosis of the leg. The administration of tamoxifen was stopped and prednisolone was reduced to 10 mg. As her malnutrition progressed, she succumbed to death of gram negative sepsis. The patient was concluded to have liver infarction and extensive venous thrombosis as a side effect of tamoxifen.
ABSTRACT
Encapsulating peritoneal sclerosis (EPS) is a potentially fatal complication after long-term peritoneal dialysis, and tamoxifen can be used for its prevention and treatment. However, tamoxifen is known to increase the risk of venous thromboembolism. A 49-year-old woman was admitted with sudden abdominal pain. The patient had received peritoneal dialysis for 20 years and switched to hemodialysis after the diagnosis of EPS. Tamoxifen (10 mg) and prednisolone (20 mg) had been administered for 8 months. On computed tomography, the left hepatic lobe was hardly illuminated, leading to a diagnosis of liver infarction. A month later, she was re-admitted due to abdominal pain and extensive deep vein thrombosis of the leg. The administration of tamoxifen was stopped and prednisolone was reduced to 10 mg. As her malnutrition progressed, she succumbed to death of gram negative sepsis. The patient was concluded to have liver infarction and extensive venous thrombosis as a side effect of tamoxifen.
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PURPOSE: Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression. MATERIALS AND METHODS: We employed public glioma datasets, Repository of Molecular Brain Neoplasia Data and The Cancer Genome Atlas, to analyze SEMA3A mRNA expression in human GBM specimens. We also evaluated for protein expression level of SEMA3A via tissue microarray (TMA) analysis. Cell migration and proliferation kinetics were assessed in various GBM patient-derived cells (PDCs) and U87-MG cell-line for SEMA3A antibody efficacy. GBM patient-derived xenograft (PDX) models were generated to evaluate tumor inhibitory effect of anti-SEMA3A antibody in vivo. RESULTS: By combining bioinformatics and TMA analysis, we discovered that SEMA3A is highly expressed in human GBM specimens compared to non-neoplastic tissues. We developed three different anti-SEMA3A antibodies, in fully human IgG form, through screening phage-displayed synthetic antibody library using a classical panning method. Neutralization of SEMA3A significantly reduced migration and proliferation capabilities of PDCs and U87-MG cell line in vitro. In PDX models, treatment with anti-SEMA3A antibody exhibited notable tumor inhibitory effect through down-regulation of cellular proliferative kinetics and tumor-associated macrophages recruitment. CONCLUSION: In present study, we demonstrated tumor inhibitory effect of SEMA3A antibody in GBM progression and present its potential relevance as a therapeutic agent in a clinical framework.
Subject(s)
Humans , Antibodies , Brain , Brain Neoplasms , Cell Line , Cell Movement , Computational Biology , Dataset , Down-Regulation , Genome , Glioblastoma , Glioma , Heterografts , Immunoglobulin G , In Vitro Techniques , Kinetics , Macrophages , Mass Screening , Methods , RNA, Messenger , Semaphorin-3AABSTRACT
BACKGROUND: In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer. METHODS: We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012. RESULTS: Patients were divided into two groups according to multiplicity (single, n = 4,744; multiple, n = 1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p < .001). Patients with multiple masses tended to have luminal A molecular subtype (p < .001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p = .016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p = .019 and p = .032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor–positive, and human epidermal growth factor receptor 2 (HER2)–negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p = .031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p = .025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS. CONCLUSIONS: Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1–2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.
Subject(s)
Humans , Breast Neoplasms , Breast , Chemotherapy, Adjuvant , Disease-Free Survival , Joints , Korea , Lymph Nodes , Multivariate Analysis , Neoplasm Metastasis , Neoplasm Staging , Phenobarbital , Prognosis , ErbB Receptors , SeoulABSTRACT
OBJECTIVE: Hemodialysis patients may have psychological distress and reduced quality of life (QoL) related to chronic physical health problems. Genetic polymorphisms associated with reduced QoL in hemodialysis patients. The aim of this study was to investigate the relationship between genetic polymorphisms and variation in health-related QoL in Korean hemodialysis patients. METHODS: The 36-item Short-Form Health Survey and the Korean Hospital Anxiety and Depression Scale were used to assess health-related QoL and psychological distress, respectively. Twenty hundred and five clinically stable patients from 6 hemodialysis centers have participated with informed consents. Sociodemographic factors, clinical factors, and genotypes of serotonin 1A receptor, brain-derived neurotrophic factors, and glucocorticoid receptor were assessed. Independent t-tests, correlation analyses, multiple regression analyses were performed for statistical analyses. RESULTS: The serotonin 1A receptor CC genotype group showed significantly higher physical and mental QoL levels than those with the GG/GC genotypes. In the final linear regression analysis, serotonin 1A receptor CC genotype was significantly associated with positive physical and mental QoL levels. CONCLUSION: ConclusionaaSerotonin 1A receptor polymorphism, as well as age and depression, were significantly associated with mental and physical QoL in hemodialysis patients. Functional activity in the serotonin receptor system may have a modulating effect on health-related QoL in hemodialysis patients.
Subject(s)
Humans , Anxiety , Brain-Derived Neurotrophic Factor , Depression , Genotype , Health Surveys , Linear Models , Polymorphism, Genetic , Quality of Life , Receptor, Serotonin, 5-HT1A , Receptors, Glucocorticoid , Renal Dialysis , SerotoninABSTRACT
PURPOSE: Hematotoxicity following anti-cancer treatment is known to be related to treatment efficacy in several malignancies. The purpose of this study was to examine the hematologic parameters related to the tumor response and survival in patients treated with curative surgery following preoperative chemoradiotherapy (CRT) for rectal cancer. MATERIALS AND METHODS: Four hundred eighteen patients with rectal cancer who underwent preoperative CRT and curative surgery were analyzed, retrospectively. The main clinical factors and blood cell counts before and after CRT were investigated with respect to their relationships with tumor downstaging and patient survival. RESULTS: The post-CRT leukocyte count was significantly different between the tumor downstaging group and the nondownstaging group (median, 4740/uL vs. 5130/uL; p = 0.013). Multivariate analysis showed that histological grade, circumferential extent, and post-CRT leukocyte count were related to tumor downstaging. In addition, histological grade, post-CRT leukocyte count, and tumor downstaging were related to disease-free survival. The 5-year disease-free survival and overall survival in patients with post-CRT leukocyte count ≤3730/uL, which is the cut-off value derived from the receiver operation characteristic (ROC) curve analysis, were significantly higher than those with higher counts (88.0% vs. 71.6%, p = 0.001; 94.4% vs. 84.1%, p = 0.024). CONCLUSION: Post-CRT leukocyte count of ≤3730/uL could be regarded as a good prognostic factor for tumor response and survival in rectal cancer patients treated with preoperative CRT.
Subject(s)
Humans , Blood Cell Count , Chemoradiotherapy , Disease-Free Survival , Leukocyte Count , Leukocytes , Leukopenia , Multivariate Analysis , Radiation Effects , Rectal Neoplasms , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: Hematotoxicity following anti-cancer treatment is known to be related to treatment efficacy in several malignancies. The purpose of this study was to examine the hematologic parameters related to the tumor response and survival in patients treated with curative surgery following preoperative chemoradiotherapy (CRT) for rectal cancer. MATERIALS AND METHODS: Four hundred eighteen patients with rectal cancer who underwent preoperative CRT and curative surgery were analyzed, retrospectively. The main clinical factors and blood cell counts before and after CRT were investigated with respect to their relationships with tumor downstaging and patient survival. RESULTS: The post-CRT leukocyte count was significantly different between the tumor downstaging group and the nondownstaging group (median, 4740/uL vs. 5130/uL; p = 0.013). Multivariate analysis showed that histological grade, circumferential extent, and post-CRT leukocyte count were related to tumor downstaging. In addition, histological grade, post-CRT leukocyte count, and tumor downstaging were related to disease-free survival. The 5-year disease-free survival and overall survival in patients with post-CRT leukocyte count ≤3730/uL, which is the cut-off value derived from the receiver operation characteristic (ROC) curve analysis, were significantly higher than those with higher counts (88.0% vs. 71.6%, p = 0.001; 94.4% vs. 84.1%, p = 0.024). CONCLUSION: Post-CRT leukocyte count of ≤3730/uL could be regarded as a good prognostic factor for tumor response and survival in rectal cancer patients treated with preoperative CRT.
Subject(s)
Humans , Blood Cell Count , Chemoradiotherapy , Disease-Free Survival , Leukocyte Count , Leukocytes , Leukopenia , Multivariate Analysis , Radiation Effects , Rectal Neoplasms , Retrospective Studies , Treatment OutcomeABSTRACT
Scrub typhus, caused by Orientia tsutsugamushi, is an acute febrile illness. Characteristics of tsutsugamushi disease are fever, rash and eschar. However, severe complications might rarely occur, such as acute fulminant myocarditis caused by scrub typhus. Thus, there are few reports of recovery from seriously complicated cases. We report on an adult male with scrub typhus complicated with acute fulminant myocarditis with no previous comorbid illness who recovered successfully with proper treatment including antibiotics, ventilator support, percutaneous cardiopulmonary support, and continuous renal replacement therapy.
Subject(s)
Adult , Humans , Male , Anti-Bacterial Agents , Exanthema , Extracorporeal Circulation , Fever , Myocarditis , Orientia tsutsugamushi , Renal Replacement Therapy , Scrub Typhus , Ventilators, MechanicalABSTRACT
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm characterized by sustained neutrophilia, splenomegaly, and hypercellular bone marrow without Philadelphia chromosome. Diagnosis of CNL requires exclusion of identifiable causes of reactive neutrophilia, such as infection and tumors. Our patient presented with general weakness and weight loss. Computed tomography (CT) showed a mass in the distal rectum, which was confirmed to be an adenocarcinoma by colonoscopic biopsy. Positron emission tomography-CT showed multiple liver, bone, and lymph node metastases. Liver and lymph node biopsies revealed neutrophilic infiltration with no evidence of adenocarcinoma. The pathological findings of the bone marrow were compatible with CNL. Cytogenetic analysis revealed a normal karyotype, and molecular analysis was negative for BCR/ABL. Here, we present a 73 year-old man diagnosed with concurrent CNL and rectal cancer.
Subject(s)
Humans , Adenocarcinoma , Biopsy , Bone Marrow , Cytogenetic Analysis , Diagnosis , Electrons , Karyotype , Leukemia , Leukemia, Neutrophilic, Chronic , Leukemoid Reaction , Leukocytosis , Liver , Lymph Nodes , Neoplasm Metastasis , Neutrophils , Philadelphia Chromosome , Rectal Neoplasms , Rectum , Splenomegaly , Weight LossABSTRACT
A 56-year-old woman with emphysematous pyelonephritis underwent an emergent left nephrectomy due to her religious creed. Postoperative hemoglobin level was decreased to 4.4 g/dL from preoperative value of 13.9 g/dL. The patient completely recovered without transfusion and was discharged on the 40th postoperative day without complication.
Subject(s)
Female , Humans , Middle Aged , Anemia , Nephrectomy , PyelonephritisABSTRACT
PURPOSE: The expression of p53 in patients with rectal cancer who underwent preoperative chemoradiationand and its potential prognostic significance were evaluated. MATERIALS AND METHODS: p53 expression was examined using immunohistochemistry in pathologic specimens from 210 rectal cancer patients with preoperative chemoradiotherapy and radical surgery. All patients were classified into two groups according to the p53 expression: low p53 ( or =50%) groups. RESULTS: p53 expression was significantly associated with tumor location from the anal verge (p=0.036). In univariate analysis, p53 expression was not associated with disease-free survival (p=0.118) or local recurrence-free survival (p=0.089). Multivariate analysis showed that tumor distance from the anal verge (p=0.006), ypN category (p=0.011), and perineural invasion (p=0.048) were independent predictors of disease-free survival; tumor distance from the anal verge was the only independent predictor of local recurrence-free survival. When the p53 groups were subdivided according to ypTNM category, disease-free survival differed significantly in patients with ypN+ disease (p=0.027) only. CONCLUSION: Expression of p53 in pathologic specimens as measured by immunohistochemical methods may have a significant prognostic impact on survival in patients with ypN+ rectal cancer with preoperative chemoradiotherapy. However, it was not an independent predictor of recurrence or survival.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Chemoradiotherapy , Disease-Free Survival , Immunohistochemistry , Multivariate Analysis , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Preoperative Care , Prognosis , Rectal Neoplasms/diagnosis , Tumor Suppressor Protein p53/analysisABSTRACT
PURPOSE: Sporadic colorectal cancers with high-frequency microsatellite instability (MSI-H) are related to hypermethylation of mismatch repair (MMR) genes and a higher frequency of BRAF mutations than Lynch syndrome. We estimated the feasibility of hereditary colorectal cancer based on hMLH1 methylation and BRAF mutations. METHODS: Between May 2005 and June 2011, we enrolled all 33 analyzed patients with MSI-H cancer (male:female, 23:10; mean age, 65.5 +/- 9.4 years) from a prospectively maintained database that didn't match Bethesda guidelines and who had results of hMLH1 methylation and BRAF mutations. RESULTS: Among the 33 patients, hMLH1 promoter methylation was observed in 36.4% (n = 12), and was not significantly related with clinicopathologic variables, including MLH1 expression. BRAF mutations were observed in 33.3% of the patients (n = 11). Four of 11 and five of 22 patients with MSI-H colon cancers were BRAF mutation (+)/hMLH1 promoter methylation (-) or BRAF mutation (-)/hMLH1 promoter methylation (+). Of the 33 patients, 21.2% were BRAF mutation (+)/hMLH1 promoter methylation (+), indicating sporadic cancers. Seventeen patients (51.5%) were BRAF mutation (-)/hMLH1 promoter methylation (-), and suggested Lynch syndrome. CONCLUSION: Patients with MSI-H colorectal cancers not fulfilling the Bethesda guidelines possibly have hereditary colorectal cancers. Adding tests of hMLH1 promoter methylation and BRAF mutations can be useful to distinguish them from sporadic colorectal cancers.
Subject(s)
Humans , Colonic Neoplasms , Colorectal Neoplasms , Colorectal Neoplasms, Hereditary Nonpolyposis , DNA Mismatch Repair , Methylation , Microsatellite Instability , Prospective StudiesABSTRACT
PURPOSE: Mesenchymal stem cells (MSCs) are surfacing as a new method of treatment for various diseases that have poor outcome with drug treatments. In this study, we investigated the effects of MSCs in a murine intestinal inflammation model mimicking human Crohn's disease (CD) using 2,4,5-trinitrobenzene sulfonic acid (TNBS). METHODS: Colitis was induced by rectal administration of 2 mg of TNBS in 35% ethanol as experimental group compared to control group. Histological changes, surface molecules of T and B cells of the spleen and blood, and cytokine production (IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, and IL-12) were determined among 3 groups comprised of control group, TNBS group and TNBS/MSC group. RESULTS: In the mice treated with MSCs, there was a decrease in the wasting disease process and inflammatory histopathological changes. There was also a decrease in pro-inflammatory T-helper 1 (Th1) cytokines IFN-gamma and IL-12 and T-helper 2 (Th2) cytokine IL-4. Anti-inflammatory cytokine IL-10 increased in mice treated with MSCs compared to colitic mice. The blood CD4+CD25+ T-regulatory cells also increased and splenic CD19 B-cells decreased. CONCLUSION: The results of this study suggest that MSCs may have a therapeutic effect in controlling the Th1 and Th2 mediated immune response in patients with CD and aid in tissue regeneration.
Subject(s)
Animals , Humans , Mice , Administration, Rectal , B-Lymphocytes , Colitis , Crohn Disease , Cytokines , Ethanol , Inflammation , Inflammatory Bowel Diseases , Interleukin-10 , Interleukin-12 , Interleukin-4 , Interleukin-6 , Mesenchymal Stem Cells , Regeneration , Spleen , Tumor Necrosis Factor-alpha , Wasting SyndromeABSTRACT
This study was designed to isolate Ca2+-activated K+ current (IKCa) and elucidate its physiological significance in freshly isolated interstitial cells of Cajal (ICCs) of guinea-pig stomach. Single ICC was freshly isolated by enzymatically dissociating from myenteric border of gastric antrum free of circular muscles, and conventional whole-cell voltage clamp technique including immunohistochemical techniques were employed to characterize the cells: In myenteric border of gastric antrum, ICC-MY (ICCs from myenteric border) were detected by immunohistochemical reactivity, and single ICC-MY which has many branches was immunohistochemically c-Kit positive. Under K+-rich and 0.1 mM ethylene glycol-bis (2-aminoethyl ether)-N,N,N',N'-tetraacetic acid pipette solution, ICC produced spontaneous inward current (-256+/-92.2 pA). When step-depolarizing pulse from -80 to +80 mV was applied at holding potential (Vh) of -80 mV, voltage-dependent outward currents were recorded with superimposed spontaneous transient outward currents (STOCs). Both STOCs and outward currents were reversibly affected by tetraethylammonium chloride (TEA) and iberiotoxin (IbTX); 2 mM TEA and 200 nM IbTX completely abolished STOCs and significantly inhibited outward K+ current over the whole potential range tested for current/voltage (I/V) relationship. In addition, TEA delayed repolarization phase of spontaneous inward current. The present results indicate the presence of IKCa in a single ICC, and it might be involved in regulation of repolarizing phase of spontaneous inward current in guinea-pig stomach.
Subject(s)
Animals , Calcium/metabolism , Guinea Pigs , Membrane Potentials/drug effects , Patch-Clamp Techniques , Peptides/pharmacology , Potassium Channels/drug effects , Proto-Oncogene Proteins c-kit/metabolism , Pyloric Antrum/cytology , Tetraethylammonium/pharmacologyABSTRACT
BACKGROUND: The objective of this study is to determine the expression pattern of G1-S inhibitor molecules in normal trophoblasts and gestational trophoblastic diseases, including hydatidiform moles and choriocarcinoma. METHODS: A total of 157 cases comprising 47 normal placentas and 110 gestational trophoblastic diseases such as choriocarcinoma (19 cases) and hydatidiform moles (91 cases of which 58 were complete, 12 were partial and 21 were invasive mole) were immunohistochemically analyzed on paraffin blocks using anti-p21, antip27, anti-p16, anti-p53, anti-pRb antibodies. RESULTS: The results revealed that in the normal placenta, all the G1-S cell cycle inhibitors were maximally expressed by the first-trimester trophoblasts and these levels decreased with gestational age. The expression of p21 and p53 was greatly enhanced in the gestational trophoblastic diseases, particularly in invasive mole and choriocarcinoma, whereas the p27 expression was significantly downregulated in choriocarcinoma. Especially, Rb expression was typically enhanced in the invasive mole, but not in choriocarcinoma. The expression level of p16 was low in all the cases, and particularly in choriocarcinoma. CONCLUSIONS: In conclusion, we demonstrated that the expression of G1/S cell cycle inhibitors correlates well with normal trophoblast differentiation, and these expressions are considerably altered in the gestational trophoblastic diseases, including complete/partial/ invasive hydatidiform mole and choriocarcinoma.