ABSTRACT
BACKGROUND: Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. METHODS: Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19-related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. RESULTS: Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. CONCLUSION: This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19's impact on GN.
ABSTRACT
A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy.
Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Retrospective Studies , Transplant Recipients , Graft Rejection/pathology , Graft Survival , Allografts , Biopsy , Kidney/pathologyABSTRACT
Tuberculous pericarditis is an extrapulmonary manifestation of tuberculosis that is most commonly associated with pericardial thickening, effusion, and calcification. We present a case of tuberculous pericarditis mimicking a malignant pericardial tumor in a 77-year-old male. CT revealed an irregular and nodular pericardial thickening. MRI revealed high signal intensity on T1-weighted fat-suppressed images and peripheral rim enhancement after gadolinium administration. MRI can be helpful in determining the differential diagnoses in cases of tuberculous pericarditis with nonspecific imaging findings.
ABSTRACT
Campylobacter jejuni is a major cause of foodborne illnesses worldwide and is primarily transmitted to humans through contaminated poultry meat. To control this pathogen, it is critical to understand its cold tolerance because poultry products are usually distributed in the cold chain. However, there is limited information regarding how this thermotolerant, microaerophilic pathogen can survive in cold and aerobic environments in the poultry cold chain. In this study, we investigated the cold tolerance of C. jejuni by measuring the viability of 90 C. jejuni strains isolated from retail raw chicken at 4 °C under aerobic and microaerobic conditions. Despite the microaerophilic nature of C. jejuni, under aerobic conditions, C. jejuni exhibited higher viability at 4 °C and required an extended inactivation time compared to microaerobic conditions. Some strains were highly tolerant to refrigeration temperatures and exhibited increased survival at 4 °C. These cold-tolerant strains mostly belonged to multilocus sequence typing (MLST) clonal complex (CC)-21 and CC-443, indicating that cold tolerance is associated with the phylogeny of C. jejuni. Notably, cold-tolerant strains had an increased probability of illness and were more likely to cause human infections due to their extended survival on refrigerated chicken meat compared to those sensitive to cold stress. Furthermore, the majority of cold-tolerant strains exhibited elevated aerotolerance, indicating that cold tolerance is related to aerotolerance. These findings suggest that refrigeration of chicken meat under aerobic conditions may not be effective at controlling C. jejuni and that cold-tolerant C. jejuni can pose an increased risk to food safety.
Subject(s)
Campylobacter jejuni , Animals , Humans , Campylobacter jejuni/genetics , Multilocus Sequence Typing , Meat , Cold Temperature , Food SafetyABSTRACT
BACKGROUND/AIM: Most deaths from colon cancer are due to metastasis. Recently, PGE2 was found to influence colon cancer invasion and metastasis. 15-PGDH, an enzyme that metabolizes PGE2, is known as a tumor suppressor in colonic carcinogenesis. This study investigated the effect of 15-PGDH on colon cancer metastasis. MATERIALS AND METHODS: 15-PGDH expression by immunohistochemical staining, clinicopathologic features, and 5-year cancer-specific survival were investigated in colon cancer patients. Liver metastasis was examined by assaying 15-PGDH activity in an animal model. Changes in PGE2, proliferation, migration, and invasion of the colorectal cancer cell line HCT116, were examined using a 15-PGDH inhibitor (SW033291) or enhancer (CDDO-ME). The expression of genes involved in the epithelial-to-mesenchymal transition (EMT) was also studied. RESULTS: The absence of 15-PGDH expression significantly correlated with advanced-stage, lymph node metastasis, and decreased cancer-specific survival in colon cancer patients. Inhibition of 15-PGDH increased colon cancer liver metastasis in the animal model. The 15-PGDH inhibitor, SW033291, increased PGE2 and decreased 15-PGDH expression on HCT116. However, treatment with CDDO-ME, a substance that enhances 15-PGDH, showed the opposite results. Inhibition of 15-PGDH increased cell proliferation, migration, and invasion, but activation of 15-PGDH showed the opposite effect. Inhibition of 15-PGDH also affected the EMT markers, N-cadherin, Snail, and Twist2. CONCLUSION: 15-PGDH inhibition increased colon cancer metastasis by inducing changes in EMT-related genes via an increase in PGE2 expression and could be a promising biomarker for anticancer treatment.
Subject(s)
Colonic Neoplasms , Liver Neoplasms , Animals , Up-Regulation , Dinoprostone/metabolism , Hydroxyprostaglandin Dehydrogenases/genetics , Hydroxyprostaglandin Dehydrogenases/metabolism , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Epithelial-Mesenchymal Transition/genetics , Cadherins/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Cell Line, Tumor , Gene Expression Regulation, NeoplasticABSTRACT
We previously demonstrated that interferon γ (IFN-γ) derived from donor T cells co-opts the indoleamine 2,3-dioxygenase 1 (IDO1) â aryl hydrocarbon receptor (AHR) axis to suppress idiopathic pneumonia syndrome (IPS). Here we report that the dysregulated expression of AP-1 family genes in Ahr-/- lung epithelial cells exacerbated IPS in allogeneic bone marrow transplantation settings. AHR repressed transcription of Jund by preventing STAT1 from binding to its promoter. As a consequence, decreased interleukin-6 impaired the differentiation of CD4+ T cells toward Th17 cells. IFN-γ- and IDO1-independent induction of Ahr expression indicated that the AHR agonist might be a better therapeutic target for IPS than the IDO1 activator. We developed a novel synthetic AHR agonist (referred to here as PB502) that potently inhibits Jund expression. PB502 was highly effective at inducing AHR activation and ameliorating IPS. Notably, PB502 was by far superior to the endogenous AHR ligand, L-kynurenine, in promoting the differentiation of both mouse and human FoxP3+ regulatory CD4+ T cells. Our results suggest that the IDO1-AHR axis in lung epithelial cells is associated with IPS repression. A specific AHR agonist may exhibit therapeutic activity against inflammatory and autoimmune diseases by promoting regulatory T-cell differentiation.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Pneumonia , Receptors, Aryl Hydrocarbon/metabolism , Animals , CD4-Positive T-Lymphocytes/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Interferon-gamma/metabolism , Mice , Pneumonia/drug therapy , Signal Transduction , T-Lymphocytes, Regulatory/metabolismABSTRACT
This study aimed to develop a mathematical model for the survival of Clostridium perfringens in hamburgers and sandwiches and to evaluate their microbial risk. The primary model was developed in hamburgers using 4 strains of C. perfringens at 5, 10, 15, 25 and 37 °C, and the kinetic parameters of the primary model were fitted well with the Weibull model (R 2 ≥ 0.95). The secondary model was developed and validated in hamburgers and sandwiches using the Davey model, which was evaluated by B f , A f , and RMSE values within the acceptable range. A probabilistic risk model was developed and simulated using @Risk program to estimate the probability of infection (P inf ) of C. perfringens based on the data on prevalence (n = 100), time, temperature, and consumption of hamburgers and sandwiches (150.00 ± 20.96 g). Based on the simulation model, the mean C. perfringens exposure dose was 0.00976 CFU/g, and the estimated mean P inf was 1.78 × 10-13, which was very low in comparison with the current available data. The proposed model and the result can thus be useful to establish risk management options and microbial criteria for C. perfringens contamination in hamburgers and sandwiches. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-01000-z.
ABSTRACT
The objective of the study was to develop a predictive model of Salmonella spp. growth in pasteurized liquid egg white (LEW) and to estimate the salmonellosis risk using the baseline model and scenario analysis. Samples were inoculated with six strains of Salmonella, and bacterial growth was observed during storage at 10-37 °C. The primary models were developed using the Baranyi model for LEW. For the secondary models, the obtained specific growth rate (µmax) and lag phase duration were fitted to a square root model and Davey model, respectively, as functions of temperature (R2 ≥ 0.98). For µmax, the values were satisfied within an acceptable range (Af, Bf: 0.70-1.15). The probability of infection (Pinf) due to the consumption of LEW was zero in the baseline model. However, scenario analysis suggested possible salmonellosis for the consumption of LEW. Because Salmonella spp. proliferated much faster in LEW than in egg white (EW) during storage at 20 and 30 °C (p < 0.01), greater Pinf may be obtained for LEW when these products are stored at the same conditions. The developed predictive model can be applied to the risk management of Salmonella spp. along the food chain, including during product storage and distribution.
ABSTRACT
Chordomas are rare, locally aggressive bone malignancies with poor prognoses. However, those with minimal or no bone involvement are more easily resectable because of their well-delineated margins and thus have better prognoses. Such extraosseous chordomas of the spine are localized both intradurally and extradurally. Only a few case reports have focused on extraosseous, extradural spinal chordomas. Radiologically, this type of chordoma has a dumbbell shape; however, dumbbell-shaped spinal tumors are traditionally thought to be neurogenic tumors (i.e., schwannomas or neurofibromas). We herein report a unique case involving a woman with a dumbbell-shaped extraosseous chordoma protruding predominantly into the retropharyngeal space. A 44-year-old woman presented for evaluation of a left submandibular mass. A T2-hyperintense, gadolinium-enhancing mass was found in her cervical spinal canal, protruding through the C2/3 neural foramen into the retropharyngeal space with minimal vertebral involvement. The initial diagnosis was a neurogenic tumor, most likely a schwannoma. After subtotal removal, the pathologic diagnosis was a chordoma. Because chordomas and schwannomas have significantly different prognoses, caution is warranted when a dumbbell-shaped tumor is identified in the spine with minimal or no vertebral deterioration on radiology. This report also provides the first thorough review of extraosseous dumbbell-shaped intraspinal-extraspinal chordomas.
Subject(s)
Chordoma , Neurilemmoma , Spinal Cord Neoplasms , Spinal Neoplasms , Adult , Chordoma/diagnostic imaging , Chordoma/surgery , Female , Humans , Magnetic Resonance Imaging , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/surgeryABSTRACT
The two primary mechanisms by which iodinated contrast media (CM) causes contrast-induced acute kidney injury (CIAKI) are the hemodynamic effect causing intrarenal vasoconstriction and the tubular toxic effect causing acute tubular necrosis. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades prostaglandin E2 (PGE2), promotes tissue repair and regeneration in many organs. PGE2 causes intrarenal arterial vasodilation. In this study, we investigated whether a 15-PGDH inhibitor can act as a candidate for blocking these two major mechanisms of CIAKI. We established a CIAKI mouse model by injecting a 10 gram of iodine per body weight (gI/kg) dose of iodixanol into each mouse tail vein. A 15-PGDH inhibitor (SW033291), PGE1, or PGE2 were administered to compare the renal functional parameters, histologic injury, vasoconstriction, and renal blood flow changes. In addition, human renal proximal tubular epithelial cells were cultured in a CM-treated medium. SW033291, PGE1, or PGE2 were added to compare any changes in cell viability and apoptosis rate. CIAKI mice that received SW033291 had lower serum levels of creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1 (p < 0.001); lower histologic injury score and TUNEL positive rates (p < 0.001); and higher medullary arteriolar area (p < 0.05) and renal blood flow (p < 0.001) than CM + vehicle group. In cell culture experiments, Adding SW033291 increased the viability rate (p < 0.05) and decreased the apoptosis rate of the tubular epithelial cells (p < 0.001). This 15-PGDH inhibitor blocks the two primary mechanisms of CIAKI, intrarenal vasoconstriction and tubular cell toxicity, and thus has the potential to be a novel prophylaxis for CIAKI. Abbreviations: 15-PGDH: 15-hydroxyprostaglandin dehydrogenase; AMP: adenosine monophosphate; CIAKI: contrast-induced acute kidney injury; CM: contrast media; EP: prostaglandin E2 receptor; hRPTECs: human-derived renal proximal tubule epithelial cells; KIM-1: kidney injury molecule-1; MTT: 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NGAL: neutrophil gelatinase-associated lipocalin; PBS: phosphate-buffered saline; PGE1: prostaglandin E1; PGE2: prostaglandin E2; RBF: renal blood flow; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; α-SMA: α-Smooth muscle actin.
Subject(s)
Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Contrast Media/adverse effects , Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors , Pyridines/pharmacology , Thiophenes/pharmacology , Animals , Creatinine/blood , Female , Humans , Kidney/physiopathology , Lipocalin-2/blood , Mice , Mice, Inbred C57BL , Prostaglandins E/pharmacology , Triiodobenzoic Acids/adverse effectsABSTRACT
PURPOSE: The establishment of a preclinical model of the abscopal effect on hepatocellular carcinoma (HCC) and evaluation of whether the hypofractionated radiation therapy (RT) multitumor Hepa1-6 mouse HCC model could be used to suppress nonradiated tumor mass was performed in this study. METHODS AND MATERIALS: Hepa1-6 mouse liver cancer cell lines were used to form tumors. Immunogenicity was analyzed using ELISpot and immune cell labeled antibody. Interferon (IFN) ß expression was confirmed through polymerase chain reaction. RESULTS: After investigation, the intratumoral transcription of type â IFN increased by 2-fold. The antitumor immune response to Hepa 1-6 cells induced by radiation was increased. Moreover, the influx of activated CD8+ T cells was increased in nonirradiated tumors. The number of dendritic cells and activation status were evaluated by flow cytometry on the second day after irradiation. Flow cytometry revealed a significantly increased dendritic cell population expressing the CD11c molecule in tumor-draining lymph nodes. Furthermore, because irradiation leads to adaptation of immune resistance of tumor cells against RT, we sought to elucidate a potent tool to overcome the resistance and confirm the ability of PD-L1 antibody to survive late RT resistance. CONCLUSIONS: The immunologic mechanism of the abscopal effect was revealed and the application of PD-L1 inhibitor successfully performed as a breakthrough in late RT resistance in the Hepa1-6 tumor model.
Subject(s)
Carcinoma, Hepatocellular/therapy , Immune Checkpoint Inhibitors/therapeutic use , Liver Neoplasms/therapy , Radiation Tolerance/immunology , Radiosurgery/methods , Animals , Antineoplastic Agents , B7-H1 Antigen/administration & dosage , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism , CD11 Antigens/metabolism , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/radiation effects , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Combined Modality Therapy/methods , Dendritic Cells/cytology , Dendritic Cells/immunology , Dendritic Cells/radiation effects , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Interferon Type I/metabolism , Interferon-beta/metabolism , Interferon-gamma/immunology , Interferon-gamma/metabolism , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Lymph Nodes/metabolism , Lymphocytes, Tumor-Infiltrating/cytology , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/radiation effects , Mice , Mice, Inbred C57BL , Neoplasm Transplantation , Radiation Dose Hypofractionation , Reverse Transcriptase Polymerase Chain Reaction , Tumor Burden/radiation effectsABSTRACT
In the present study, we demonstrated the marked activity of SW033291, an inhibitor of 15-hydoxyprostaglandin dehydrogenase (15-PGDH), in preventing acute kidney injury (AKI) in a murine model of ischemia-reperfusion injury. AKI due to ischemic injury represents a significant clinical problem. PGE2 is vasodilatory in the kidney, but it is rapidly degraded in vivo due to catabolism by 15-PGDH. We investigated the potential of SW033291, a potent and specific 15-PGDH inhibitor, as prophylactic treatment for ischemic AKI. Prophylactic administration of SW033291 significantly increased renal tissue PGE2 levels and increased post-AKI renal blood flow and renal arteriole area. In parallel, prophylactic SW033291 decreased post-AKI renal morphology injury scores and tubular apoptosis and markedly reduced biomarkers of renal injury that included blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Prophylactic SW033291 also reduced post-AKI induction of proinflammatory cytokines, high-mobility group box 1, and malondialdehyde. Protective effects of SW033291 were mediated by PGE2 signaling, as they could be blocked by pharmacological inhibition of PGE2 synthesis. Consistent with activation of PGE2 signaling, SW033291 induced renal levels of both EP4 receptors and cAMP, along with other vasodilatory effectors, including AMP, adenosine, and the adenosine A2A receptor. The protective effects of SW0333291 could largely be achieved with a single prophylactic dose of the drug. Inhibition of 15-PGDH may thus represent a novel strategy for prophylaxis of ischemic AKI in multiple clinical settings, including renal transplantation and cardiovascular surgery.
Subject(s)
Acute Kidney Injury/prevention & control , Adenosine/metabolism , Dinoprostone/metabolism , Enzyme Inhibitors/pharmacology , Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors , Kidney/blood supply , Kidney/drug effects , Pyridines/pharmacology , Receptor, Adenosine A2A/metabolism , Receptors, Prostaglandin E, EP4 Subtype/metabolism , Renal Circulation/drug effects , Reperfusion Injury/prevention & control , Thiophenes/pharmacology , Vasodilation/drug effects , Acute Kidney Injury/enzymology , Acute Kidney Injury/pathology , Acute Kidney Injury/physiopathology , Animals , Blood Flow Velocity , Disease Models, Animal , Hydroxyprostaglandin Dehydrogenases/metabolism , Kidney/enzymology , Kidney/pathology , Male , Mice, Inbred C57BL , Reperfusion Injury/enzymology , Reperfusion Injury/pathology , Reperfusion Injury/physiopathology , Signal TransductionABSTRACT
BACKGROUND: Various animal models have been introduced into the study of liver metastasis of colorectal cancer, but they have not been compared under the same conditions. The aim of this study was to identify an optimized mouse model that showed a high rate of hepatic metastasis and expression of clonal dynamics. MATERIALS AND METHODS: Athymic nude mice (n=30) were divided into two equal groups for the creation of a splenic injection model (SIM) and surgically orthotopic implantation model (SOIM) of liver metastasis of colorectal cancer using HCT116 cells. Hepatic metastasis was confirmed by gross and microscopic examinations. Expression of MET transcriptional regulator MACC1 (MACC1) in colon cancer cell lines and metastatic tumors in the group with a higher liver metastasis rate was confirmed by quantitative reverse-transcription-polymerase chain reaction. RESULTS: The observation time was significantly shorter for SIM than for SOIM (33.0±6.8 vs. 41.2±7.2 days, p<0.001). The rate of hepatic metastasis was significantly higher in SIM than in SOIM (76.9% vs. 38.4%, p=0.038). MACC1 was expressed in Colo201, HCT116, HT29, LS513, SW620, and WiDr cells but not in SW480 cells. All hepatic metastases in SIM mice expressed MACC1, and metastatic HCT116 cells had significantly greater expression than did the original HCT116 cells (p<0.001). CONCLUSION: With a higher rate of hepatic metastasis with clonal dynamics in a shorter observation time than the SOIM, SIM appears to be a good animal model for identifying new targets and in drug development for colorectal cancer liver metastasis. SOIM should also be considered for the study of the full steps of metastasis.
Subject(s)
Colorectal Neoplasms/complications , Liver Neoplasms/secondary , Animals , Cell Line, Tumor , Colorectal Neoplasms/pathology , Disease Models, Animal , Female , Humans , Liver Neoplasms/pathology , Mice , Mice, Nude , Neoplasm MetastasisABSTRACT
OBJECTIVES: The aims of this study were to clarify the activation of complement pathways in patients with lupus nephritis (LN), and to elucidate the association between these complement activation types and clinical outcomes. METHODS: We enrolled 115 patients with biopsy-proven LN from 2003 to 2016 from the lupus cohort at the Busan Paik Hospital and the Jeju National University Hospital in Korea. The patients were divided into two groups based on the patterns of glomerular complements deposits. The presence of C1q, C4 and/or C3 deposits in the glomerulus was considered evidence for the activation of the classical pathway with or without alternative pathway activation (group 1, N = 93), and glomerular C3 deposition without C1q and C4 deposits was considered as a marker for the alternative pathway limited activation (group 2, N = 22). The study end point was progression of kidney disease defined as a ≥50% reduction in estimated glomerular filtration rate from baseline values or advancement to end-stage renal disease. RESULTS: The mean estimated glomerular filtration rate and median urine protein-to-creatinine ratio of the patients were 85.7 ± 32.4 mL/min/1.73 m2 and 3.1 g/g, respectively, at the time of kidney biopsy. Forty-nine patients (43%) had nephrotic range of proteinuria. Compared to group 1 patients, those in group 2 were older, were more likely to be males and were more hypertensive. In addition, plasma C3 and C4 levels were significantly lower in group 1 patients compared to those in group 2. Moreover, anti-dsDNA concentration was significantly higher in group 1 patients compared to those in group 2. The mean follow-up time was 5.4 ± 3.4 years. The rates of response to one-year immunosuppressive treatment were poorer in group 2 patients compared to those in group 1. During the follow-up time, the progression of kidney disease was significantly higher in group 2 than in group 1 patients. CONCLUSION: This study showed that there was alternative complement pathway limited activation in the renal tissue in a small number of patients with LN, and these patients had worse renal outcomes compared to patients with glomerular classical complement pathway activation with or without alternative pathway activation.
Subject(s)
Complement Activation/physiology , Complement Pathway, Alternative/physiology , Kidney/pathology , Lupus Nephritis/immunology , Adult , Biomarkers/blood , Complement C1q/analysis , Complement C3/analysis , Complement C4/analysis , Disease Progression , Female , Glomerular Filtration Rate , Humans , Immunosuppressive Agents/therapeutic use , Lupus Nephritis/blood , Lupus Nephritis/drug therapy , Male , Middle Aged , Proteinuria/drug therapy , Republic of Korea , Young AdultABSTRACT
Tetrahydrobiopterin (BH4) shows therapeutic potential as an endogenous target in cardiovascular diseases. Although it is involved in cardiovascular metabolism and mitochondrial biology, its mechanisms of action are unclear. We investigated how BH4 regulates cardiovascular metabolism using an unbiased multiple proteomics approach with a sepiapterin reductase knock-out (Spr-/-) mouse as a model of BH4 deficiency. Spr-/- mice exhibited a shortened life span, cardiac contractile dysfunction, and morphological changes. Multiple proteomics and systems-based data-integrative analyses showed that BH4 deficiency altered cardiac mitochondrial oxidative phosphorylation. Along with decreased transcription of major mitochondrial biogenesis regulatory genes, including Ppargc1a, Ppara, Esrra, and Tfam, Spr-/- mice exhibited lower mitochondrial mass and severe oxidative phosphorylation defects. Exogenous BH4 supplementation, but not nitric oxide supplementation or inhibition, rescued these cardiac and mitochondrial defects. BH4 supplementation also recovered mRNA and protein levels of PGC1α and its target proteins involved in mitochondrial biogenesis (mtTFA and ERRα), antioxidation (Prx3 and SOD2), and fatty acid utilization (CD36 and CPTI-M) in Spr-/- hearts. These results indicate that BH4-activated transcription of PGC1α regulates cardiac energy metabolism independently of nitric oxide and suggests that BH4 has therapeutic potential for cardiovascular diseases involving mitochondrial dysfunction.
Subject(s)
Biopterins/analogs & derivatives , Cardiovascular Agents/pharmacology , Mitochondria, Heart/drug effects , Myocardial Contraction/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Animals , Biopterins/pharmacology , Male , Mice, Inbred C57BL , Mitochondria, Heart/metabolism , Organelle Biogenesis , Signal Transduction/drug effectsABSTRACT
Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroectodermal carcinoma arising from mechanoreceptor Merkel cells. Multiple MCCs are even rarer. We report a case of two independent MCCs simultaneously present in the cheek of a patient, which were effectively and esthetically treated using a cheek flap. Punch biopsy performed in a 60-year-old woman admitted with a chief complaint of two skin-colored hard nodules in her left cheek, accompanied by an itching sensation, was suggestive of MCC. Accordingly, we performed sentinel lymph node biopsy through the modified Blair incision under general anesthesia, in cooperation with the head and neck surgery department. The defect was covered with a cheek flap by slightly extending the existing incision following wide excision with a safety margin of 1 cm. This paper is significant in that it introduces an effective reconstruction technique that maintains function using a cheek flap for the management of this rare case. In addition, this paper is the first to classify multiple MCCs according to the time of onset. We believe that this paper presents an effective alternative reconstruction technique with sentinel node biopsy through the modified Blair incision.
ABSTRACT
PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. MATERIALS AND METHODS: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.
Subject(s)
Carcinoma in Situ/diagnosis , Endoscopic Mucosal Resection/methods , Stomach Neoplasms/diagnosis , Carcinoma in Situ/pathology , Early Detection of Cancer , Female , Humans , Male , Observer Variation , Reproducibility of Results , Retrospective Studies , Risk Factors , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND: The aims of this study are to evaluate the usefulness of submucosal deformity pattern analysis with endoscopic ultrasonography (EUS) for predicting the depth of invasion in early gastric cancer (EGC) and the treatment results of endoscopic submucosal dissection (ESD). METHODS: The endoscopic and EUS parameters of 345 patients with endoscopically suspected EGC who underwent endoscopic or surgical resection between July 2012 and May 2017 were retrospectively reviewed. All patients were classified into three categories as follows according to the morphologic type of submucosal deformity identified by EUS: (1) no submucosal deformity, (2) wedge-shaped deformity, and (3) arch-shaped deformity. The presence of an arch-shaped submucosal deformity on EUS and an active endoscopic ulcer or surrounding mucosal fold convergence/clubbing on conventional endoscopy were defined as suggestive of deep submucosal cancer invasion (SCI). RESULTS: Upper location (p = 0.034) and the presence of an arch-shaped submucosal deformity on EUS (p < 0.001) were significant predictors of deep submucosal invasion, with the presence of an arch-shaped submucosal deformity showing the highest predictive value (odds ratio of 26.27). The overall diagnostic accuracy of EUS for predicting deep SCI was 83.5%, with a sensitivity of 84.0% and a specificity of 83.3%, which were significantly higher than those of conventional endoscopy. A larger lesion size and the presence of an arch-shaped submucosal deformity were significant factors associated with noncurative resection after ESD. CONCLUSIONS: Submucosal deformity pattern analysis with EUS can provide more accurate information than conventional endoscopy for predicting deep SCI. The presence of an arch-shaped submucosal deformity on EUS was an effective predictor of deep SCI and noncurative resection.
Subject(s)
Endosonography/methods , Gastric Mucosa/pathology , Stomach Neoplasms , Aged , Early Detection of Cancer/methods , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Patient Selection , Reproducibility of Results , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Treatment OutcomeABSTRACT
Endometrial cancer is the sixth most common cancer in women worldwide. Peroxiredoxins (PRDXs) are antioxidant enzymes that serve important roles in cell differentiation, proliferation, and apoptosis. In the present study, the potential associations between PRDX expression and endometrial cancer were investigated. The expression levels of various PRDX mRNAs were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) in endometrial cancer tissues (n=26) and normal endometrial tissues (n=10). Additionally, the expression of PRDX isoforms was immunohistochemically examined in endometrial cancer tissues and adjacent normal endometrial tissues from 42 patients. Finally, the associations between high PRDX expression levels and clinicopathological features were examined in patients with endometrial cancer. Analysis of PRDX expression in endometrial cancer tissues and normal endometrial tissues by semi-quantitative RT-PCR showed that all PRDX isoforms had increased expression in the endometrial cancer tissues compared with that in the normal endometrium, and the differences in the expression levels of PRDX1 and PRDX3 between cancer and normal tissues were statistically significant (P=0.0015 and P=0.0134, respectively). Additionally, analysis of PRDX expression in endometrial cancer and paired normal endometrial tissues by immunohistochemistry showed strong cytoplasmic staining of PRDX3 and PRDX5 in cancer tissues, with high PRDX3 (25/42, 59.5%) and PRDX5 (32/42, 76.2%) appearing more frequently in endometrial cancer than in normal endometrial tissues (P=0.0001 and P=0.0023, respectively). Furthermore, high expression of PRDX5 was associated with advanced-stage endometrial cancer (P=0.0399). Although the 5-year survival rate was marginally higher in patients with low expression of PRDX3 and PRDX5, this result was not statistically significant. In summary, PRDX3 and PRDX5 are highly expressed in endometrial cancer and could be associated with advanced stage and poor prognosis. Therefore, these proteins may potentially be used as prognostic markers for endometrial cancer.