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1.
J Am Soc Nephrol ; 33(1): 186-200, 2022 01.
Article in English | MEDLINE | ID: mdl-34725107

ABSTRACT

BACKGROUND: Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues found in chronically inflamed organs. Although studies have documented TLT formation in transplanted kidneys, the clinical relevance of these TLTs remains controversial. We examined the effects of TLTs on future graft function using our histologic TLT maturity stages and the association between TLTs and Banff pathologic scores. We also analyzed the risk factors for the development of TLTs. METHODS: Serial protocol biopsy samples (0 hour, 1, 6, and 12 months) without rejection were retrospectively analyzed from 214 patients who underwent living donor kidney transplantation. TLTs were defined as lymphocyte aggregates with signs of proliferation and their stages were determined by the absence (stage I) or presence (stage II) of follicular dendritic cells. RESULTS: Only 4% of patients exhibited TLTs at the 0-hour biopsy. Prevalence increased to almost 50% at the 1-month biopsy, and then slightly further for 12 months. The proportion of advanced stage II TLTs increased gradually, reaching 19% at the 12-month biopsy. Presence of stage II TLTs was associated with higher risk of renal function decline after transplantation compared with patients with no TLT or stage I TLTs. Stage II TLTs were associated with more severe tubulitis and interstitial fibrosis/tubular atrophy at 12 months and predicted poorer graft function independently from the degree of interstitial inflammation. Pretransplantation rituximab treatment dramatically attenuated the development of stage II TLTs. CONCLUSIONS: TLTs are commonly found in clinically stable transplanted kidneys. Advanced stage II TLTs are associated with progressive graft dysfunction, independent of interstitial inflammation.


Subject(s)
Choristoma/pathology , Kidney Diseases/pathology , Kidney Transplantation/adverse effects , Lymphoid Tissue , Primary Graft Dysfunction/etiology , Primary Graft Dysfunction/pathology , Adult , Aged , Biopsy , Female , Glomerular Filtration Rate , Humans , Kidney Diseases/surgery , Male , Middle Aged , Retrospective Studies
2.
J Am Soc Nephrol ; 31(12): 2855-2869, 2020 12.
Article in English | MEDLINE | ID: mdl-33046532

ABSTRACT

BACKGROUND: Depletion of ATP in renal tubular cells plays the central role in the pathogenesis of kidney diseases. Nevertheless, inability to visualize spatiotemporal in vivo ATP distribution and dynamics has hindered further analysis. METHODS: A novel mouse line systemically expressing an ATP biosensor (an ATP synthase subunit and two fluorophores) revealed spatiotemporal ATP dynamics at single-cell resolution during warm and cold ischemic reperfusion (IR) with two-photon microscopy. This experimental system enabled quantification of fibrosis 2 weeks after IR and assessment of the relationship between the ATP recovery in acute phase and fibrosis in chronic phase. RESULTS: Upon ischemia induction, the ATP levels of proximal tubule (PT) cells decreased to the nadir within a few minutes, whereas those of distal tubule (DT) cells decreased gradually up to 1 hour. Upon reperfusion, the recovery rate of ATP in PTs was slower with longer ischemia. In stark contrast, ATP in DTs was quickly rebounded irrespective of ischemia duration. Morphologic changes of mitochondria in the acute phase support the observation of different ATP dynamics in the two segments. Furthermore, slow and incomplete ATP recovery of PTs in the acute phase inversely correlated with fibrosis in the chronic phase. Ischemia under conditions of hypothermia resulted in more rapid and complete ATP recovery with less fibrosis, providing a proof of concept for use of hypothermia to protect kidney tissues. CONCLUSIONS: Visualizing spatiotemporal ATP dynamics during IR injury revealed higher sensitivity of PT cells to ischemia compared with DT cells in terms of energy metabolism. The ATP dynamics of PTs in AKI might provide prognostic information.


Subject(s)
Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Adenosine Triphosphate/metabolism , Kidney Tubules, Proximal/metabolism , Kidney Tubules, Proximal/pathology , Acute Kidney Injury/etiology , Animals , Disease Models, Animal , Mice , Predictive Value of Tests , Prognosis , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Time Factors
3.
Arerugi ; 69(8): 683-688, 2020.
Article in Japanese | MEDLINE | ID: mdl-32963192

ABSTRACT

The case involved a man in his forties. While working at the restaurant that the patient runs, the patient experienced a stab-like pain on the left shoulder and developed systemic pruritic eruptions. He was diagnosed with anaphylaxis upon visiting our emergency department. Conjunctival hyperemia, lip swelling, cold sweats, and nausea presented later. A cap fluorescence enzyme immunoassay using the serum of the patient showed specific immunoglobulin E (IgE) positivity for wasps; therefore, we hypothesized that he had anaphylaxis caused by the insect's sting. Insects of the same species as that by which the patient had been stung were collected and finally identified as the Asian needle ant (Brachyponera chinensis). The freeze-dried insects' bodies were sonicated into powders and stored for following examinations. Next, a basophil activation test was performed using the patient's whole blood treated with the reagent above, which showed positivity. Furthermore, a skin prick test using the same reagent showed a positive result, and the reaction increased in a concentrationdependent manner. Based on these results, the patient was diagnosed with anaphylaxis after a sting by the ant. Based on the results of the allergen component specific IgE test, we speculated that the pathogens in this case was group5 allergen of the Asian needle ant. Anaphylaxis following insect stings by this ant has been reported frequently in South Korea. However, it is quite rare in Japan, although the ant is native to Japan. Clinicians should consider that this allergy can occur indoors, unlike allergies to other types of venom.


Subject(s)
Anaphylaxis , Ants , Bites and Stings/complications , Adult , Anaphylaxis/etiology , Animals , Humans , Immunoglobulin E , Japan , Male , Pain
5.
J Cell Biochem ; 117(9): 2001-9, 2016 09.
Article in English | MEDLINE | ID: mdl-26773721

ABSTRACT

Transcription factors and culture media were investigated to determine the condition to initiate the differentiation of human-induced pluripotent stem (iPS) cells most efficiently. The expression of genes in human adult liver was compared with that in 201B7 cells (iPS cells) using cDNA microarray analysis. Episomal plasmids expressing transcription factors were constructed. 201B7 cells were transfected with the episomal plasmids and cultured in ReproFF (feeder-free media maintaining pluripotency), Leibovitz-15 (L15), William's E (WE), or Dulbecco's modified Eagle medium/Nutrient F-12 Ham (DF12) for 7 days. RNA was isolated and subjected to real-time quantitative PCR to analyze the expression of alpha-feto protein (AFP) and albumin. cDNA microarray analysis revealed 16 transcription factors that were upregulated in human adult liver relative to that in 201B7 cells. Episomal plasmids expressing these 16 genes were transfected into 201B7 cells. CCAAT/enhancer-binding protein alpha (CEBPA), CCAAT/enhancer-binding protein beta (CEBPB), forkhead box A1 (FOXA1), and forkhead box A3 (FOXA3) up-regulated AFP and down-regulated Nanog. These four genes were further analyzed. The expression of AFP and albumin was the highest in 201B7 cells transfected with the combination of CEBPA, CEBPB, FOXA1, and FOXA3 and cultured in WE. The combination of CEBPA, CEBPB, FOXA1, and FOXA3 was suitable for 201B7 cells to initiate differentiation to the hepatocyte lineage and WE was the most suitable medium for culture after transfection. J. Cell. Biochem. 117: 2001-2009, 2016. © 2016 Wiley Periodicals, Inc.


Subject(s)
Cell Differentiation , Culture Media , Hepatocytes/metabolism , Induced Pluripotent Stem Cells/metabolism , Transcription Factors , Cell Differentiation/drug effects , Cell Differentiation/genetics , Cell Line , Culture Media/chemistry , Culture Media/pharmacology , Hepatocytes/cytology , Humans , Induced Pluripotent Stem Cells/cytology , Transcription Factors/biosynthesis , Transcription Factors/genetics
7.
Pediatr Int ; 58(10): 979-983, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26865117

ABSTRACT

BACKGROUND: Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder affecting the transport of cationic amino acid caused by mutations in solute carrier family 7 amino acid transporter light chain, y+ L system, member 7 (SLC7A7). This disorder occurs worldwide, especially in Finland and Japan, where founder effect mutations have been reported. Detailed features of the clinical symptoms and mutation types in Japanese LPI, however, remain unclear to date. METHODS: An epidemiological nationwide survey of LPI patients was carried out via mail to all domestic university and general hospitals in Japan. Next, the clinical information for each LPI patient was obtained, in the form of a questionnaire, from the attending physicians who replied to the letters. RESULTS: We received answered questionnaires for 43 LPI patients in 19 hospitals. We selected 35 patients who were genetically diagnosed with LPI. The most common clinical manifestations were with protein aversion, ferritinemia, increased serum lactate dehydrogenase, and hyperammonemia. The most frequent SLC7A7 mutation in Japanese LPI patients is p.R410*, which is a founder effect mutation in northern Japan. In total, nine types of mutation were detected in this survey, six of which (p.R410*, p.S238F, c.1630delC, p.S489P, c.1673delG, and IVS3-IVS5del9.7 kb) have not been reported in other countries. CONCLUSION: The clinical and genetic features of 35 Japanese patients with LPI were characterized, and no correlation between genotype and phenotype was observed. The importance of early diagnosis for better prognosis of LPI is emphasized.


Subject(s)
Amino Acid Metabolism, Inborn Errors/epidemiology , Amino Acid Transport System y+/genetics , DNA/genetics , Mutation , Adolescent , Adult , Amino Acid Metabolism, Inborn Errors/genetics , Amino Acid Metabolism, Inborn Errors/metabolism , Amino Acid Transport System y+/metabolism , Child , Child, Preschool , DNA Mutational Analysis , Female , Genotype , Humans , Incidence , Infant , Infant, Newborn , Japan/epidemiology , Male , Phenotype , Young Adult
8.
J Cell Biochem ; 116(8): 1479-89, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25683148

ABSTRACT

Human induced pluripotent stem (hiPS) cells are an ideal source for hepatocytes. Glucose and arginine are necessary for cells to survive. Hepatocytes have galactokinase (GALK), which metabolizes galactose for gluconeogenesis, and ornithine transcarbamylase (OTC), which converts ornithine to arginine in the urea cycle. Hepatocyte selection medium (HSM) lacks both glucose and arginine, but contains galactose and ornithine. Although human primary hepatocytes survive in HSM, all the hiPS cells die in 3 days. The aim of this study was to modify HSM so as to initiate hepatocyte differentiation in hiPS cells within 2 days. Hepatocyte differentiation initiating medium (HDI) was prepared by adding oncostatin M (10 ng/ml), hepatocyte functional proliferation inducer (10 nM), 2,2'-methylenebis (1,3-cyclohexanedione) (M50054) (100 µg/ml), 1× non-essential amino acid, 1× sodium pyruvate, nicotinamide (1.2 mg/ml), L-proline (30 ng/ml), and L-glutamine (0.3 mg/ml) to HSM. HiPS cells (201B7 cells) were cultured in HDI for 2 days. RNA was isolated, used as template for cDNA, and subjected to real-time quantitative polymerase chain reaction. Alpha-fetoprotein, γ-glutamyl transpeptidase, and delta-like 1 were upregulated. Expression of albumin was not observed. Expression of transcription factors specific to hepatocytes was upregulated. The expression of GALK2, OTC, and CYP3A4 were increased. In conclusion, differentiation of 201B7 cells to hepatoblast-like cells was initiated in HDI. Limitations were small number of cells were obtained, and the cells with HDI were not mature hepatocytes.


Subject(s)
Culture Media/chemistry , Culture Media/pharmacology , Gene Expression Regulation/drug effects , Hepatocytes/cytology , Induced Pluripotent Stem Cells/drug effects , Cell Differentiation , Cell Line , Cell Survival/drug effects , Cytochrome P-450 CYP3A/genetics , Galactokinase/genetics , Galactokinase/pharmacology , Glutamine/pharmacology , Hepatocytes/drug effects , Humans , Oncostatin M/pharmacology , Ornithine Carbamoyltransferase/genetics , Proline/pharmacology
9.
Abdom Imaging ; 40(8): 3012-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26350283

ABSTRACT

PURPOSE: Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) strongly contrasts cancerous tissue against background healthy tissues. Positron emission tomography/computed tomography (PET/CT) applies the uptake of 18-fluorodeoxyglucose in the diagnosis of cancer. Our aim was to compare DWIBS/T2 and PET/CT in patients with upper gastrointestinal cancers. METHODS: Patient records, including imaging results from July 2012 to March 2015, were analyzed retrospectively. Four men (age, 72.5 ± 5.3 years) and ten women (age, 71.6 ± 4.0 years) were enrolled in this study. The numbers of patients with esophageal cancer, gastric cancer, gastrointestinal stromal tumor, and duodenal cancer were one, eight, three, and two, respectively. RESULTS: Six out of eight patients with gastric cancer had positive results on both DWIBS/T2 and PET/CT. The diameter and depth of invasion of gastric cancer was larger in patients with positive DWIBS/T2 and PET/CT findings than those with negative findings. These results suggested that patients with gastric cancer with larger pixel numbers might tend to show positive results with DWIBS/T2. CONCLUSIONS: DWIBS/T2 and PET/CT have similar sensitivity for the diagnosis of upper gastrointestinal cancer. The diameter and depth of invasion affected the detectability of gastric cancer.


Subject(s)
Diffusion Magnetic Resonance Imaging , Gastrointestinal Neoplasms/diagnosis , Multimodal Imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Whole Body Imaging , Aged , Female , Fluorodeoxyglucose F18 , Humans , Male , Radiopharmaceuticals , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Upper Gastrointestinal Tract/diagnostic imaging , Upper Gastrointestinal Tract/pathology
10.
Hepatogastroenterology ; 62(138): 463-5, 2015.
Article in English | MEDLINE | ID: mdl-25916083

ABSTRACT

BACKGROUND/AIMS: One major problem with Intraductal papillary mucinous neoplasm (IPMN) is the appearance of pancreatic duct adenocarcinoma. Diffusion-weighted whole body imaging with background body signal suppression (DWIBS) provides hyperintense signals in cases of cancer. DWIBS and T2 image fusion (DWIBS/T2) provides functional information in anatomical settings, and is useful for the detection of cancer with strong contrast against surrounding tissues. DWIBS/T2 signals were analyzed in patients with IPMN to investigate positive or negative results. METHODOLOGY: Patient records were analyzed retrospectively regarding IPMN. None showed high-risk stigmata or worrisome features. To rule out T2 shine-through or differentiate malignant lesions from non-malignant causes of restricted diffusion, positive ADC maps were produced from the recorded ADC values. RESULTS: None of the patients with IPMN had features of malignant progression. No mural nodules were detected by endoscopic ultrasonography. IPMN was hyperintense with DWIBS/T2 and the ADC map. This finding suggested that the hyperintense values of IPMN were T2 shine-through. These results showed that none of the IPMNs were positive with DWIBS/T2. CONCLUSION: DWIBS/T2 was negative for patients with IPMN. DWIBS/T2 might be useful for the evaluation of malignant progression, in addition to observation.


Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Diffusion Magnetic Resonance Imaging , Image Interpretation, Computer-Assisted , Neoplasms, Cystic, Mucinous, and Serous/pathology , Pancreatic Neoplasms/pathology , Aged , Aged, 80 and over , Diagnosis, Differential , Humans , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies
11.
Hepatogastroenterology ; 62(138): 295-8, 2015.
Article in English | MEDLINE | ID: mdl-25916052

ABSTRACT

BACKGROUND/AIMS: The aim of this study was to identify factors affecting the detection of colorectal cancer (CRC) and colon polyps (CPs) using abdominal ultrasonography (US). METHODOLOGY: Patient records were analyzed retrospectively. Those diagnosed as having either CRC or CPs by colonoscopy performed after screening abdominal US were enrolled. The diagnostic criterion for CRC was an irregularly thickened wall or mass. CPs were diagnosed as spherical or ovoid hypoechoic lesions arising within the colonic lumen as seen on abdominal US. RESULTS: Sixteen patients had a total of 16 CRC lesions and 11 patients had a total of 17 CPs. All CRC lesions invaded deeper than the subserosa. Cancer cell invasion limited to the submucosa was noted in the two 1.5-cm CPs. Detection of these lesions was not associated with invasion to lymph or blood vessels. These results suggest that wall thickening might be the consequence of cancer cells invading below the subserosa, thereby resulting in the lesions becoming detectable on abdominal US. CONCLUSIONS: Detection of CRC and CPs on abdominal US was associated with lesion size and depth of invasion.


Subject(s)
Colon/diagnostic imaging , Colonic Polyps/diagnostic imaging , Colorectal Neoplasms/diagnostic imaging , Intestinal Mucosa/diagnostic imaging , Aged , Aged, 80 and over , Colon/pathology , Colonic Polyps/pathology , Colonoscopy , Colorectal Neoplasms/pathology , Female , Humans , Intestinal Mucosa/pathology , Male , Neoplasm Invasiveness , Predictive Value of Tests , Retrospective Studies , Tumor Burden , Ultrasonography
12.
Hepatogastroenterology ; 61(130): 291-5, 2014.
Article in English | MEDLINE | ID: mdl-24901126

ABSTRACT

BACKGROUND/AIMS: The early diagnosis of acute cholangitis (AC) is critical for appropriate treatment. METHODOLOGY: Patient records from April 2008 to December 2012 were retrospectively analyzed. Data on white blood cell count and levels of C-reactive protein, total-bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase (gamma-GTP) were collected from AC patients on the day they underwent endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and treatment. Data were collected 3 months before ERCP to analyze the rate of change of these variables. Receiver operating characteristics curve analysis was performed. RESULTS: We enrolled 63 patients with AC and 65 patients with non-AC. The threshold values of ALP and gamma-GTP were 1.09 and 1.30, respectively. CONCLUSIONS: 450 (IU/L) and 100 (IU/L), respectively, were thresholds of ALP and gamma-GTP on the day of ERCP. 1.09 and 1.30, respectively, were thresholds of ALP and gamma-GTP rates of change for the diagnosis of AC.


Subject(s)
Alkaline Phosphatase/blood , Cholangitis/blood , Cholangitis/epidemiology , gamma-Glutamyltransferase/blood , Acute Disease , Aged , Aged, 80 and over , Cholangiopancreatography, Endoscopic Retrograde , Cholangitis/diagnostic imaging , Cholangitis/surgery , Female , Humans , Male , Middle Aged , Retrospective Studies , Statistics, Nonparametric
13.
J Thorac Dis ; 16(1): 264-272, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38410610

ABSTRACT

Background: In flexible bronchoscopy, endobronchial ultrasonography using a guide sheath (EBUS-GS) has varying diagnostic yield depending on the findings of radial-endobronchial ultrasonography (R-EBUS). The diagnosis rate is lower when the ultrasound probe is "adjacent to", than when it is "within" the lesion. However, these findings are inconsistent, and the imaging status may change from "adjacent to" to "within" as examination progresses. In this study, we analyzed the predictive factors for this change, which remain unexplored till date. Methods: Patients who underwent flexible bronchoscopic biopsy with EBUS-GS at Kameda Medical Centre between 1 April 2014 and 31 March 2019 were included in this retrospective cohort study. Patients without "adjacent to" lesions were excluded. The appearance of "A to W" (the change from "adjacent to" to "within" imaging status) was the primary outcome. Based on multivariate regression and receiver operating characteristic curve analysis, we evaluated the discriminative properties of the factors strongly correlated with "A to W". Results: In total, 260 patients were included in this study. In 84 cases, the R-EBUS findings were "A to W". No such findings were observed in 176 cases. The mean lesion diameter was significantly larger (P=0.021) in the group with "A to W" than in the group without. The odds ratio [1.023 (1.003-1.046)] for lesion diameter showed statistical significance in the multivariable regression model. The sensitivity and specificity were 0.346 and 0.852, respectively, at the optimal threshold (29.25 mm) set using the Youden index. Conclusions: We found that lesion diameter was a significant factor in predicting "A to W", with a cut-off value of 29.25 mm and high specificity (0.852).

14.
J Cell Biochem ; 114(3): 584-8, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22991093

ABSTRACT

Feeder-free culture of human induced pluripotent stem (hiPS) cells is necessary for their clinical application to avoid adverse effects of foreign proteins. hiPS cells were cultured with combinations of activin (A), CHIR99021 (C), basic fibroblast growth factor (F), and leukemia inhibitory factor (L) under feeder-free conditions. Culture was terminated after 12 passages or when the cell morphology changed from pluripotency. Pluripotency was analyzed by alkaline phosphatase (ALP) staining and immunostaining with antibodies to Oct3/4, Nanog, SSEA4, and TRA-1-60. SB431542 (SB), an activin inhibitor, was added to the culture, and the morphology of the cells was observed. hiPS cells cultured with A, AC, and ACL after 12 passages were positive for ALP staining. Oct3/4 was positive in hiPS cells cultured with A, AC, and ACL. hiPS cells were positive for Nanog when cultured with A and AC; however, Nanog signal was weaker in cells cultured with ACL. SSEA4 was positive in hiPS cells cultured with A and AC but almost negative in those cultured with ACL. hiPS cells were positive for TRA-1-60 when cultured with A, AC, and ACL. hiPS cells lose their undifferentiated morphology at six passages when cultured with A + SB, five passages with AC + SB, and nine passages with ACL. We conclude that feeder-free culture of hiPS cells requires A or AC to maintain pluripotency.


Subject(s)
Activins/pharmacology , Cell Culture Techniques , Feeder Cells , Induced Pluripotent Stem Cells/metabolism , Pyridines/pharmacology , Pyrimidines/pharmacology , Activins/antagonists & inhibitors , Alkaline Phosphatase/analysis , Animals , Antigens, Surface/analysis , Benzamides/pharmacology , Collagen , Dioxoles/pharmacology , Drug Combinations , Fibroblast Growth Factor 2/pharmacology , Homeodomain Proteins/analysis , Humans , Laminin , Leukemia Inhibitory Factor/pharmacology , Mice , Nanog Homeobox Protein , Octamer Transcription Factor-3/analysis , Proteoglycans/analysis , Stage-Specific Embryonic Antigens/analysis
15.
Hepatogastroenterology ; 60(123): 517-21, 2013 May.
Article in English | MEDLINE | ID: mdl-23635445

ABSTRACT

BACKGROUND/AIMS: To clarify the usefulness of screening ultrasonography (US) to diagnose gastric and colorectal cancer, patient records were analyzed retrospectively. METHODOLOGY: Ultrasonography was performed for patients with abdominal symptoms. They were then subjected to computed tomography (CT) when diagnosed with gastric cancer, colorectal cancer, or bowel obstruction. Patient records were analyzed retrospectively after final diagnosis of gastric cancer or colorectal cancer by endoscopy, surgery or necropsy. RESULTS: Twelve patients were diagnosed with colorectal cancer and six with gastric cancer. The detailed structure of colorectal cancer was visible as wall thickening with US, while cancer was often illustrated as a mass by CT. Loss of stratification was clear with US in 11 patients. US demonstrated wall thickening in 10 patients and a mass in 1 patient, while CT demonstrated wall thickening in 3 patients and a mass in 8 patients. The structure of colorectal cancer was more obvious when using US than when using CT. One patient demonstrated focal wall thickening with US, but this was not detected by CT. CONCLUSIONS: US is useful for diagnosis of gastric cancer and colorectal cancer. US produces more detailed findings in colorectal cancer than CT.


Subject(s)
Colorectal Neoplasms/diagnostic imaging , Mass Screening/methods , Stomach Neoplasms/diagnostic imaging , Aged , Aged, 80 and over , Analysis of Variance , Colorectal Neoplasms/pathology , Endoscopy, Gastrointestinal , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Predictive Value of Tests , Retrospective Studies , Stomach Neoplasms/pathology , Tomography, X-Ray Computed , Ultrasonography
16.
Respir Med Case Rep ; 45: 101892, 2023.
Article in English | MEDLINE | ID: mdl-37577121

ABSTRACT

Parvimonas micra is a gram-positive anaerobic coccus (GPAC) that colonizes the oral cavity and gastrointestinal tract. Recent advances in bacterial identification have confirmed the clinical importance of Parvimonas micra. Here, we report a case of empyema with bacteremia caused by Parvimonas micra. We successfully treated the patient with the appropriate antibiotics and drainage. Parvimonas micra can cause respiratory infections, including empyema, which can progress to bacteremia if treatment is delayed. In Parvimonas micra infections, not only the oral cavity but also the entire body must be investigated to clarify the entry mechanism.

17.
Circulation ; 124(12): 1382-90, 2011 Sep 20.
Article in English | MEDLINE | ID: mdl-21859969

ABSTRACT

BACKGROUND: The role of hepatic ATP-binding cassette transporter 1 (ABCA1) in maintaining plasma high density lipoprotein cholesterol (HDL-C) levels is well established, but its role in reverse cholesterol transport (RCT) is unclear. Probucol is a compound that reduces HDL-C levels but also reduces atherosclerosis in animal models and xanthomas in humans. The aim of the present study was to test the hypothesis that probucol inhibits hepatic ABCA1 activity, thereby reducing HDL-C levels but promoting RCT from macrophages. METHODS AND RESULTS: Wild-type (WT) C57BL/6 mice and scavenger receptor class B type I (SR-BI) knockout mice were fed a chow diet containing 0.5% probucol or normal chow for 2 weeks. In WT mice, probucol, despite decreasing HDL-C by >80%, effectively maintained macrophage RCT. In SR-BI knockout mice, probucol also substantially reduced HDL-C but significantly increased macrophage RCT. Furthermore, probucol significantly enhanced the excretion of HDL-derived cholesterol into feces in both WT and SR-BI knockout mice. Probucol inhibited ABCA1-dependent cholesterol efflux from mouse primary hepatocytes, and this effect was shown to be responsible for the effect of probucol on increasing the fecal excretion of HDL-derived cholesterol in vivo. CONCLUSIONS: We demonstrate that pharmacological inhibition of hepatic ABCA1 activity with probucol reduced HDL-C levels but promoted RCT through diversion of HDL-derived cholesterol from efflux back into plasma instead to excretion in the bile. These results explain the beneficial effects of probucol on atherosclerosis and xanthomas despite its HDL-lowering effects and suggest that inactivation of hepatic ABCA1 leads to increased RCT despite reducing plasma HDL-C levels.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Atherosclerosis/metabolism , Cholesterol, HDL/blood , Hepatocytes/metabolism , Macrophages/metabolism , ATP Binding Cassette Transporter 1 , ATP-Binding Cassette Transporters/genetics , Animals , Anticholesteremic Agents/pharmacology , Atherosclerosis/prevention & control , Biliary Tract/metabolism , Biological Transport/drug effects , Biological Transport/physiology , Cells, Cultured , Cholesterol, HDL/pharmacokinetics , Disease Models, Animal , Hepatocytes/cytology , Hepatocytes/drug effects , Humans , Macrophages/cytology , Macrophages/drug effects , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Knockout , Probucol/pharmacology , Xanthomatosis/metabolism , Xanthomatosis/prevention & control
18.
J Cell Biochem ; 113(8): 2714-20, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22441995

ABSTRACT

Insulin-like growth factor (IGF)-I is up-regulated in pancreatic cancer tissues. Pancreatic cancer cell lines were analyzed in serum-free media as a model of the fibrous tissues that these cells often invade. Pancreatic cancer surgical specimens were immunostained with anti-IGF-I receptor (IGF-IR)ß antibody. The growth of pancreatic cancer cells in serum-free media was also analyzed. Cell lysates were analyzed for protein by western blot analysis. Cells cultured in the presence of picropodophyllin (PPP), LY294002, or PD98059, were subjected to cell proliferation and scratch assays. In addition, BrdU uptake and apoptosis were analyzed in these cells. IGF-IRß was detected in pancreatic cancer cells invading fibrous tissues. NOR-P1 grew most rapidly in serum-free media. The concentrations of IGF-I and IGF-II in the media were higher in NOR-P1 than the other cell lines. Cell proliferation in NOR-P1 cells was enhanced by IGF-I or IGF-II treatment more than in MIA-Paca2 or PK-1 cells. PPP, LY294002, and PD98059 suppressed proliferation and motility of NOR-P1 cells and inhibited BrdU uptake, while PPP induced apoptosis. IGF-IRß may be a potential therapeutic target to inhibit invasion of pancreatic cancer.


Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Receptor, IGF Type 1/metabolism , Cell Line, Tumor , Culture Media, Serum-Free , Deoxyuridine/pharmacology , Humans , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor I/pharmacology , Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor II/pharmacology
19.
Cell Mol Biol Lett ; 17(3): 459-78, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22706677

ABSTRACT

Secretory phospholipases A(2) (sPLA(2)s) are a diverse family of low molecular mass enzymes (13-18 kDa) that hydrolyze the sn-2 fatty acid ester bond of glycerophospholipids to produce free fatty acids and lysophospholipids. We have previously shown that group X sPLA(2) (sPLA(2)-X) had a strong hydrolyzing activity toward phosphatidylcholine in low-density lipoprotein (LDL) linked to the formation of lipid droplets in the cytoplasm of macrophages. Here, we show that group V sPLA(2) (sPLA(2)-V) can also cause the lipolysis of LDL, but its action differs remarkably from that of sPLA(2)-X in several respects. Although sPLA(2)-V released almost the same amount of fatty acids from LDL, it released more linoleic acid and less arachidonic acid than sPLA(2)-X. In addition, the requirement of Ca(2+) for the lipolysis of LDL was about 10-fold higher for sPLA(2)-V than sPLA(2)-X. In fact, the release of fatty acids from human serum was hardly detectable upon incubation with sPLA(2)-V in the presence of sodium citrate, which contrasted with the potent response to sPLA(2)-X. Moreover, sPLA(2)-X, but not sPLA(2)-V, was found to specifically interact with LDL among the serum proteins, as assessed by gel-filtration chromatography as well as sandwich enzyme-immunosorbent assay using anti-sPLA(2)-X and anti-apoB antibodies. Surface plasmon resonance studies have revealed that sPLA2-X can bind to LDL with high-affinity (K(d) = 3.1 nM) in the presence of Ca(2+). Selective interaction of sPLA(2)-X with LDL might be involved in the efficient hydrolysis of cell surface or intracellular phospholipids during foam cell formation.


Subject(s)
Arachidonic Acid , Group V Phospholipases A2/metabolism , Group X Phospholipases A2/metabolism , Linoleic Acid , Lipoproteins, HDL , Lipoproteins, LDL , Arachidonic Acid/chemistry , Arachidonic Acid/metabolism , Calcium/chemistry , Citrates/chemistry , Group V Phospholipases A2/chemistry , Group X Phospholipases A2/chemistry , Humans , Hydrolysis , Linoleic Acid/chemistry , Linoleic Acid/metabolism , Lipolysis , Lipoproteins , Lipoproteins, HDL/chemistry , Lipoproteins, HDL/metabolism , Lipoproteins, LDL/chemistry , Lipoproteins, LDL/metabolism , Phospholipids/chemistry , Phospholipids/metabolism , Protein Binding , Serum/chemistry , Serum/metabolism , Sodium Citrate , Surface Plasmon Resonance
20.
Hepatogastroenterology ; 58(109): 1156-8, 2011.
Article in English | MEDLINE | ID: mdl-21937369

ABSTRACT

BACKGROUND/AIMS: Patients with abdominal symptoms and leukocytosis or elevated C-reactive protein were subjected to abdominal ultrasonography (US) for correct diagnosis. METHODOLOGY: Patients with abdominal symptoms, leukocytosis and elevated C-reactive protein were enrolled. Those with abnormal liver enzymes or radiographs were excluded since either of them might be a clue to proper diagnosis, such as hepatobiliary diseases or bowel obstruction. RESULTS: Total number of patients was 38. Number of acute diverticulitis, colitis, acute appendicitis and enteritis were 8, 7, 7 and 6, respectively. One patient with pelvis tumor and 2 with colon cancer were successfully diagnosed with abdominal US. Colon cancers were confirmed and pelvis tumor was diagnosed as ovarian squamous cell carcinoma with surgical specimens. Sensitivity and specificity were 100% (95% CI: 44-100%) and 97.1% (95% CI: 85-99%), respectively. CONCLUSIONS: Our data clearly recommended that abdominal US be performed carefully for patients with abdominal symptoms and leukocytosis or elevated CRP since potentially they had malignancies.


Subject(s)
Abdomen/diagnostic imaging , C-Reactive Protein/analysis , Leukocytosis/diagnostic imaging , Humans , Sensitivity and Specificity , Ultrasonography
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