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1.  Intravascular large B-cell lymphoma secondary to lymphoplasmacytic lymphoma: a case report and review of literature with clonality analysis 
Intravascular large B-cell lymphoma (IVLBCL) can be a fatal malignancy mainly because of difficulty in early detection. Due to the lack of specific clinical manifestations, early detection of IVLBCL remains a challenge, especially in the presence of comorbidities. Lymphoplasmacytic lymphoma (LPL) is an indolent B-cell lymphoma accompanied by monoclonal immunoglobulin M protein in most patients, and known to be associated with high risk of secondary hematological malignancies. Here, we report a patient who developed IVLBCL during treatment for LPL that presented a diagnostic challenge. Rearrangement analysis of the immunoglobulin heavy chain revealed the different clonal origins of two lymphomas, implying a predisposition of LPL to develop unrelated secondary lymphoma. Secondary lymphoma including IVLBCL during the treatment for LPL deserves consideration in order to facilitate early diagnosis and intervention.
PMCID: PMC4440173  PMID: 26045864
Intravascular large B-cell lymphoma; lymphoplasmacytic lymphoma; secondary lymphoma; immunoglobulin rearrangement
2.  An injured tissue affects the opposite intact peritoneum during postoperative adhesion formation 
Scientific Reports  2015;5:7668.
The pathophysiology of adhesion formation needs to be clarified to reduce the adhesion-related morbidity. The epithelial characteristics of the peritoneum suggest a protective role against adhesion formation, yet how the peritoneum is involved in adhesion formation is not well characterized. We microscopically observed an experimental model of adhesion formation to investigate the effects of an injured tissue on the opposite intact peritoneum. Adhesions were induced between injured and intact hepatic lobes, and the intact peritoneum opposite to the injured tissue was examined for 8 days. The opposite intact peritoneum was denuded of mesothelial cells for 6 hours, and the remnant mesothelial cells changed morphologically for 24 hours. The detachment of mesothelial cells allowed fibrin to attach to the basement membrane of the opposite peritoneum, connecting the two lobes. Moreover, macrophages and myofibroblasts accumulated between the two lobes, and angiogenesis occurred from the opposite intact lobe to the injured lobe. These observations indicate that an injured tissue deprives the opposite intact peritoneum of its epithelial structure and causes fibrous adhesions to the opposite intact tissue. This study implies a possible role of mesothelial cells for barrier function against adhesion formation, that is, keeping mesothelial cells intact might lead to its prophylaxis.
PMCID: PMC4286739  PMID: 25566876
3.  X-ray diagnosis with a bloating agent for foreign object ingestion 
The location of an ingested foreign object is often difficult to determine by X-ray if gastric air bubbles are not clear in the image. Methods that provide negative contrast can facilitate precise object localization, which is important for object retrieval and treatment of the patient. This case report describes a male child, 2 years and 2 mo of age, who accidentally swallowed a lithium battery while playing at home. A plain X-ray showed that the battery was in the abdomen, but it was unclear whether the object was still inside the stomach. A second X-ray examination performed after oral administration of a bloating agent to produce expansion of the stomach and provide negative contrast confirmed that the ingested battery was still in the stomach. The battery was then carefully removed using magnetic and balloon catheters under fluoroscopic guidance. This case report describes the successful use of an orally administered bloating agent without pain to the child in order to determine the precise location of a foreign object in the abdomen.
PMCID: PMC4023311  PMID: 24868517
Accidental ingestion; Bloating agent; X-ray; Minimal invasion; Foreign object
4.  Recurrent Cholangitis with Congenital Hepatic Fibrosis and Pancreaticobiliary Maljunction after Roux-en-Y Reconstruction 
A 1-year-old girl had pancreaticobiliary maljunction, a choledochal cyst, and polycystic kidney. At the age of 4 years, she was treated by resection of the choledochal cyst and Roux-en-Y reconstruction because of the cyst's risk of cancer. She was diagnosed as having congenital hepatic fibrosis based on the histological findings. Postoperatively, she suffered recurrent fever of unknown origin, refractory to several antibiotics. At the age of 6 years, she underwent living donor liver transplantation from her father. Multi-drug-resistant Pseudomonas aeruginosa was cultured in the recipient's liver. After liver transplantation, she had no episodes of recurrent fever. Roux-en-Y reconstruction should be avoided for ductal plate malformations such as congenital hepatic fibrosis.
PMCID: PMC4336062  PMID: 25755951
congenital hepatic fibrosis; pancreaticobiliary maljunction; cholangitis; Roux-en-Y reconstruction; liver transplantation
5.  Low-molecular-weight lipoprotein (a) and low relative lymphocyte concentration are significant and independent risk factors for coronary heart disease in patients with type 2 diabetes mellitus: Lp(a) phenotype, lymphocyte, and coronary heart disease 
The aim of the present prospective study was to examine whether lipoprotein (a) [Lp(a)] phenotypes and/or low relative lymphocyte concentration (LRLC) are independently associated with coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM).
Serum Lp(a) concentration, Lp(a) phenotypes, and RLC were analyzed in 214 subjects. Lp(a) phenotypes were classified into 7 subtypes according to sodium dodecyl sulfate-agarose gel electrophoresis by Western blotting. Subjects were assigned to the low-molecular-weight (LMW (number of KIV repeats: 11–22) ) and high-molecular-weight (HMW( number of KIV repeats: >22 )) Lp(a) groups according to Lp(a) phenotype and to the LRLC (RLC: <20.3%) and normal RLC (NRLC; RLC: ≥20.3%) groups according to RLC. A CHD event was defined as the occurrence of angina pectoris or myocardial infarction during the follow-up period.
During the follow-up period, 30 cases of CHD events were verified. Neutrophil count showed no correlation with CHD, while relative neutrophil concentration and RLC showed positive and negative correlations, respectively, with CHD. The Cox proportional hazard model analysis revealed the following hazard ratios adjusted for LMW Lp(a), LRLC, and LMW Lp(a) + LRLC: (4.31; 95% confidence interval [CI], 1.99-9.32; P < 0.01, 3.621; 95% CI, 1.50-8.75; P < 0.05, and 7.15; 95% CI, 2.17-23.56; P < 0.01, respectively).
Our results suggest that both LMW Lp(a) and LRLC are significant and independent risk factors for CHD and that the combination thereof more strongly predicts CHD in patients with T2DM.
PMCID: PMC3606419  PMID: 23496967
Lipoprotein (a) phenotype; Relative lymphocyte concentration; Coronary heart disease
6.  Relationship between postprandial glucose level and carotid artery stiffness in patients without diabetes or cardiovascular disease 
The aim of this study was to evaluate the relationship between postprandial glucose level and atherosclerosis in patients without diabetes and cardiovascular disease by determining carotid ultrasonographic variables and serum levels of 1,5-anhydroglucitol (1,5-AG).
The subjects were 72 patients without diabetes and cardiovascular disease being treated for hypertension or dyslipidemia. The clinical characteristics of all subjects, including the serum level of 1,5-AG, which appears to be well suited for monitoring postprandial hyperglycemia, were evaluated after an overnight fast. The average intima-media thickness (IMT) and the average pulsatility index (PI) of the right and left common carotid arteries were determined with high-resolution ultrasonography and used as ultrasonographic variables. The subjects were divided into a Lower 1,5-AG group (n = 36) and a Higher 1,5-AG group (n = 36). We evaluated the relationship between clinical characteristics and ultrasonographic variables of the carotid artery in both groups.
The average PI in the Lower 1,5-AG group was significantly higher than that in the Higher 1,5-AG group, but the average IMT did not differ between the groups. Linear regression analysis, with the ultrasonographic variables as the dependent variables, with 1,5-AG as the independent variable, and adjusted for other clinical characteristics, showed significant correlation between 1,5-AG and the PI but not between 1,5-AG and IMT.
Our results suggest that postprandial hyperglycemia increases carotid artery stiffness, but not morphological change, in patients without diabetes or cardiovascular disease.
PMCID: PMC3598373  PMID: 23442745
1,5-anhydroglucitol; Pulsatility index; Postprandial glucose; Nondiabetic patients
7.  Bile Acid Binding Resin Improves Metabolic Control through the Induction of Energy Expenditure 
PLoS ONE  2012;7(8):e38286.
Besides well-established roles of bile acids (BA) in dietary lipid absorption and cholesterol homeostasis, it has recently become clear that BA is also a biological signaling molecule. We have shown that strategies aimed at activating TGR5 by increasing the BA pool size with BA administration may constitute a significant therapeutic advance to combat the metabolic syndrome and suggest that such strategies are worth testing in a clinical setting. Bile acid binding resin (BABR) is known not only to reduce serum cholesterol levels but also to improve glucose tolerance and insulin resistance in animal models and humans. However, the mechanisms by which BABR affects glucose homeostasis have not been established. We investigated how BABR affects glycemic control in diet-induced obesity models.
Methods and Findings
We evaluated the metabolic effect of BABR by administrating colestimide to animal models for the metabolic syndrome. Administration of BABR increased energy expenditure, translating into significant weight reduction and insulin sensitization. The metabolic effects of BABR coincide with activation of cholesterol and BA synthesis in liver and thermogenesis in brown adipose tissue. Interestingly, these effects of BABR occur despite normal food intake and triglyceride absorption. Administration of BABR and BA had similar effects on BA composition and thermogenesis, suggesting that they both are mediated via TGR5 activation.
Our data hence suggest that BABR could be useful for the management of the impaired glucose tolerance of the metabolic syndrome, since they not only lower cholesterol levels, but also reduce obesity and improve insulin resistance.
PMCID: PMC3430641  PMID: 22952571
8.  The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance 
Previous studies have demonstrated that postprandial hyperglycemia attenuates brachial artery flow-mediated dilation (FMD) in prediabetic patients, in diabetic patients, and even in normal subjects. We have previously reported that postprandial hyperinsulinemia also attenuates FMD. In the present study we evaluated the relationship between different degrees of postprandial attenuation of FMD induced by postprandial hyperglycemia and hyperinsulinemia and differences in ingested carbohydrate content in non-diabetic individuals.
Thirty-seven healthy subjects with no family history of diabetes were divided into 3 groups: a 75-g oral glucose loading group (OG group) (n = 14), a test meal group (TM group) (n = 12; 400 kcal, carbohydrate content 40.7 g), and a control group (n = 11). The FMD was measured at preload (FMD0) and at 60 minutes (FMD60) and 120 (FMD120) minutes after loading. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were determined at preload (PG0, IRI0) and at 30 (PG30, IRI30), 60 (PG60, IRI60), and 120 (PG120, IRI120) minutes after loading.
Percentage decreases from FMD0 to FMD60 were significantly greater in the TM group (−21.19% ± 17.90%; P < 0.001) and the OG group (−17.59% ± 26.64%) than in the control group (6.46% ± 9.17%; P < 0.01), whereas no significant difference was observed between the TM and OG groups. In contrast, the percentage decrease from FMD0 to FMD120 was significantly greater in the OG group (−18.91% ± 16.58%) than in the control group (6.78% ± 11.43%; P < 0.001) or the TM group (5.22% ± 37.22%; P < 0.05), but no significant difference was observed between the control and TM groups. The FMD60 was significantly correlated with HOMA-IR (r = −0.389; P < 0.05). In contrast, FMD120 was significantly correlated with IRI60 (r = −0.462; P < 0.05) and the AUC of IRI (r = −0.468; P < 0.05). Furthermore, the percentage change from FMD0 to FMD120 was significantly correlated with the CV of PG (r = 0.404; P < 0.05), IRI60 (r = 0.401; p < 0.05) and the AUC of IRI (r = 0.427; P < 0.05). No significant correlation was observed between any other FMDs and glucose metabolic variables.
Differences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.
PMCID: PMC3471039  PMID: 22891922
Flow-mediated dilation; Carbohydrate content; Postprandial; Glucose metabolism; Non-diabetic individuals
9.  Cajal body surveillance of U snRNA export complex assembly 
The Journal of Cell Biology  2010;190(4):603-612.
Passage of transcribed U snRNA precursors through Cajal bodies ensures that they are properly bound to the PHAX adaptor protein required for nuclear exit.
Phosphorylated adaptor for RNA export (PHAX) is the key export mediator for spliceosomal U small nuclear RNA (snRNA) precursors in metazoa. PHAX is enriched in Cajal bodies (CBs), nuclear subdomains involved in the biogenesis of small ribonucleoproteins. However, CBs’ role in U snRNA export has not been demonstrated. In this study, we show that U snRNA precursors microinjected into Xenopus laevis oocyte nuclei temporarily concentrate in CBs but gradually decrease as RNA export proceeds. Inhibition of PHAX activity by the coinjection of a specific anti-PHAX antibody or a dominant-negative PHAX mutant inhibits U snRNA export and simultaneously enhances accumulation of U snRNA precursors in CBs, indicating that U snRNAs transit through CBs before export and that binding to PHAX is required for efficient exit of U snRNAs from CBs. Similar results were obtained with U snRNAs transcribed from microinjected genes. These results reveal a novel function for CBs, which ensure that U snRNA precursors are properly bound by PHAX.
PMCID: PMC2928011  PMID: 20733056
10.  Large-scale analysis of full-length cDNAs from the tomato (Solanum lycopersicum) cultivar Micro-Tom, a reference system for the Solanaceae genomics 
BMC Genomics  2010;11:210.
The Solanaceae family includes several economically important vegetable crops. The tomato (Solanum lycopersicum) is regarded as a model plant of the Solanaceae family. Recently, a number of tomato resources have been developed in parallel with the ongoing tomato genome sequencing project. In particular, a miniature cultivar, Micro-Tom, is regarded as a model system in tomato genomics, and a number of genomics resources in the Micro-Tom-background, such as ESTs and mutagenized lines, have been established by an international alliance.
To accelerate the progress in tomato genomics, we developed a collection of fully-sequenced 13,227 Micro-Tom full-length cDNAs. By checking redundant sequences, coding sequences, and chimeric sequences, a set of 11,502 non-redundant full-length cDNAs (nrFLcDNAs) was generated. Analysis of untranslated regions demonstrated that tomato has longer 5'- and 3'-untranslated regions than most other plants but rice. Classification of functions of proteins predicted from the coding sequences demonstrated that nrFLcDNAs covered a broad range of functions. A comparison of nrFLcDNAs with genes of sixteen plants facilitated the identification of tomato genes that are not found in other plants, most of which did not have known protein domains. Mapping of the nrFLcDNAs onto currently available tomato genome sequences facilitated prediction of exon-intron structure. Introns of tomato genes were longer than those of Arabidopsis and rice. According to a comparison of exon sequences between the nrFLcDNAs and the tomato genome sequences, the frequency of nucleotide mismatch in exons between Micro-Tom and the genome-sequencing cultivar (Heinz 1706) was estimated to be 0.061%.
The collection of Micro-Tom nrFLcDNAs generated in this study will serve as a valuable genomic tool for plant biologists to bridge the gap between basic and applied studies. The nrFLcDNA sequences will help annotation of the tomato whole-genome sequence and aid in tomato functional genomics and molecular breeding. Full-length cDNA sequences and their annotations are provided in the database KaFTom via the website of the National Bioresource Project Tomato
PMCID: PMC2859864  PMID: 20350329
11.  Coexpression Analysis of Tomato Genes and Experimental Verification of Coordinated Expression of Genes Found in a Functionally Enriched Coexpression Module 
Gene-to-gene coexpression analysis is a powerful approach to infer the function of uncharacterized genes. Here, we report comprehensive identification of coexpression gene modules of tomato (Solanum lycopersicum) and experimental verification of coordinated expression of module member genes. On the basis of the gene-to-gene correlation coefficient calculated from 67 microarray hybridization data points, we performed a network-based analysis. This facilitated the identification of 199 coexpression modules. A gene ontology annotation search revealed that 75 out of the 199 modules are enriched with genes associated with common functional categories. To verify the coexpression relationships between module member genes, we focused on one module enriched with genes associated with the flavonoid biosynthetic pathway. A non-enzyme, non-transcription factor gene encoding a zinc finger protein in this module was overexpressed in S. lycopersicum cultivar Micro-Tom, and expression levels of flavonoid pathway genes were investigated. Flavonoid pathway genes included in the module were up-regulated in the plant overexpressing the zinc finger gene. This result demonstrates that coexpression modules, at least the ones identified in this study, represent actual transcriptional coordination between genes, and can facilitate the inference of tomato gene function.
PMCID: PMC2853382  PMID: 20130013
coexpression; flavonoid; Solanum lycopersicum; tomato; zinc finger
12.  Chromatographic Zinc Isotope Separation by Chelating Exchange Resin 
Chromatographia  2010;71(3-4):195-199.
Zinc isotope separations were studied by displacement chromatography using the chelating properties of malate, citrate and lactate exchange resin and EDTA as ligands. After each chromatographic operation, the heavier zinc isotopes were found to preferentially fractionated into the carboxylate complex solution phase. The separation coefficients (ε) for zinc isotope separation had the largest value and were obtained for the isotopic pairs 68Zn/64Zn (7.16 × 10−4) and 66Zn/64Zn (3.08 × 10−4), respectively, at 298 ± 1 K. The separation coefficient per unit mass differences (ε/ΔM) for the isotopic pair of 68Zn/64Zn was found to range around 1.55 × 10−4.
PMCID: PMC2827798  PMID: 20208981
Zinc isotope separation; Chelating exchange resin; Separation coefficient; Separation coefficient per unit mass differences
13.  Metabolite annotations based on the integration of mass spectral information 
The Plant Journal   2008;54(5):949-962.
A large number of metabolites are found in each plant, most of which have not yet been identified. Development of a methodology is required to deal systematically with unknown metabolites, and to elucidate their biological roles in an integrated ‘omics’ framework. Here we report the development of a ‘metabolite annotation’ procedure. The metabolite annotation is a process by which structures and functions are inferred for metabolites. Tomato (Solanum lycopersicum cv. Micro-Tom) was used as a model for this study using LC-FTICR-MS. Collected mass spectral features, together with predicted molecular formulae and putative structures, were provided as metabolite annotations for 869 metabolites. Comparison with public databases suggests that 494 metabolites are novel. A grading system was introduced to describe the evidence supporting the annotations. Based on the comprehensive characterization of tomato fruit metabolites, we identified chemical building blocks that are frequently found in tomato fruit tissues, and predicted novel metabolic pathways for flavonoids and glycoalkaloids. These results demonstrate that metabolite annotation facilitates the systematic analysis of unknown metabolites and biological interpretation of their relationships, which provide a basis for integrating metabolite information into the system-level study of plant biology.
PMCID: PMC2440531  PMID: 18266924
LC-FTICR-MS; metabolite annotations; secondary metabolites; Solanum lycopersicum; tomato
14.  ANDROLOGY: Relationships Between Sperm Motility Characteristics Assessed by the Computer-Aided Sperm Analysis (CASA) and Fertilization Rates In Vitro 
Purpose: Some studies have suggested that computer-aided sperm analysis (CASA) estimates of concentration and movement characteristics of progressively motile spermatozoa are related to fertilization rates in vitro. However, it has also been suggested that the greater number of motility parameters assessed by CASA does not imply more precision in predicting fertility. This study was carried out to investigate the relationships between the CASA estimates and fertilization rates in vitro.
Methods: Semen quality analysis was performed using CASA in 136 in vitro fertilization-embryo transfer (IVF-ET) cycles with at least 3 oocytes collected. The CASA estimates before and after swim-up were compared between 108 cycles with fertilization rate >50% (“good” group) and 28 cycles with fertilization rate ≤50% (“poor” group).
Results: Before swim-up, there were significant correlations between fertilization rates and CASA estimates, including amplitude of lateral head displacement (ALH) (r = .269), curvilinear velocity (VCL) (r = .297), straight line velocity (VSL) (r = .266), and rapid sprm movement (Rapid) (r = .243). There was also a significant correlation between the fertilization rates and straightness (STR) after swim-up (r = −0.178). As for sperm movement characteristics, there were significant differences of ALH (p < .005), VCL (p < .001), VSL (p < .005), and Rapid (p < .01) between “good” and “poor” groups before swim-up. After swim-up, there were significant differences of VCL (p < .005), average path velocity (VAP) (p < .005), and Rapid (p < .05) between the two groups.
Conclusions: These results indicate that some of the CASA estimates provide reliable estimation of the fertilizing ability of human sperm. There were significant differences of the two sperm movement characteristics, including VCL and Rapid (before and after swim-up), indicating that the total distance traveled by rapid sperm movement might be important in human sperm fertilizing abilities.
PMCID: PMC3455361
Computer-aided sperm analysis; fertilization; sperm motility
15.  A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma 
British Journal of Haematology  2014;165(6):768-776.
Although initial rituximab-containing chemotherapies achieve high response rates, indolent B-cell non-Hodgkin lymphoma (B-NHL), such as follicular lymphoma (FL), is still incurable. Therefore, new effective agents with novel mechanisms are anticipated. In this multicentre phase II study, patients with relapsed/refractory indolent B-NHL and mantle cell lymphoma (MCL) received vorinostat 200 mg twice daily for 14 consecutive days in a 21-d cycle until disease progression or unacceptable toxicity occurred. The primary endpoint was overall response rate (ORR) in FL patients and safety and tolerability in all patients. Secondary endpoints included progression-free survival (PFS). Fifty-six eligible patients were enrolled; 50 patients (39 with FL, seven with other B-NHL, and four with MCL) were evaluable for ORR, and 40 patients had received rituximab-containing prior chemotherapeutic regimens. For the 39 patients with FL, the ORR was 49% [95% confidence interval (CI): 32·4, 65·2] and the median PFS was 20 months (95% CI: 11·2, 29·7). Major toxicities were manageable grade 3/4 thrombocytopenia and neutropenia. Vorinostat offers sustained antitumour activity in patients with relapsed or refractory FL with an acceptable safety profile. Further investigation of vorinostat for clinical efficacy is warranted.
PMCID: PMC4282031  PMID: 24617454
vorinostat; indolent B-cell non-Hodgkin lymphoma; follicular lymphoma; phase II trial; HAT mutation
16.  Urinary N-acetyl-β-d-Glucosaminidase Levels are Positively Correlated With 2-Hr Plasma Glucose Levels During Oral Glucose Tolerance Testing in Prediabetes 
Urinary N-acetyl-β-D-glucosaminidase (NAG) excretion is increased in patients with impaired glucose tolerance (IGT). This study investigated when during the oral glucose tolerance test (OGTT) the plasma glucose, urine glucose, and insulin levels correlate most strongly with urinary N-acetyl-β-d-glucosaminidase (NAG) levels in prediabetic subjects.
The OGTT was administered to 80 subjects who had not yet received a diagnosis of diabetes mellitus (DM) and in whom HbA1c levels were ≤6.8% and fasting plasma glucose levels were <7.0 mmol/l. Forty-two subjects had normal glucose tolerance (NGT), 31 had impaired glucose tolerance (IGT), and 7 had DM according to World Health Organization criteria. Serum levels of cystatin C, the estimated glomerular filtration rate, the urinary albumin-to-creatinine (Cr) ratio, urinary and serum β2-microglobulin, and urinary NAG were measured as markers of renal function.
NAG levels were significantly higher in subjects with DM and in subjects with IGT than in subjects with NGT. No significant associations were observed between glycemic status and other markers of renal function. Multiple linear regression analysis showed that the NAG level was positively correlated with plasma glucose levels at 120 min of the OGTT and was associated with the glycemic status of prediabetic patients.
These results suggest that postprandial hyperglycemia is an independent factor that causes renal tubular damage in prediabetes patients.
PMCID: PMC3558795  PMID: 23143631
cystatin C; N-acetyl-β-d-glucosaminidase; tubular dysfunction; impaired glucose tolerance; diabetic nephropathy

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