High-sensitive XANES analysis at Ce L2-edge for Ce in bauxites using transition-edge sensors: Implications for Ti-rich geological samples.

Accurate determination of cerium (Ce) valence state is important for interpreting the Ce anomaly in geological archives for (paleo)redox reconstruction. However, the routine application of Ce L3-edge X-ray absorption near-edge structure (XANES) spectroscopy for detecting trace Ce in geological samples can often be restricted by coexisting titanium (Ti) due to the proximity of their fluorescence emission lines. Therefore, the signal-to-noise ratio of Ce L3-edge XANES spectra may not be sufficiently high for high-quality spectroscopic analysis. This study introduces a semi-quantitative approach appropriate for Ti-rich, Ce-dilute geological materials by synchrotron-based X-ray measurement at the Ce L2-edge. First, the results confirm that Ce L2-edge XANES spectra are able to avoid overlapping Ti Kß emissions and provide more reliable information on the Ce valence state in Ti-rich materials relative to L3-edge XANES. Moreover, the application of transition-edge sensor (TES) could reach the higher sensitivity with better energy resolution than conventional silicon drift detector (SDD) to detect fluorescence X-ray (Ce Lß1). The investigation on bauxites developed from the Columbia River Basalts shows that combining Ce L2-edge XANES and TES allows for resolving weak Ce fluorescence lines at the L2-edge from Ti-rich, Ce-dilute samples (Ti/Ce mass ratio up to ∼6000, tens of ppm Ce). The outcome emphasizes the practical possibility of investigating Ce redox state in Ti-rich geological samples.

[A case of pembrolizumab responding to recurrent small bowel mucinous adenocarcinoma with Peutz-Jeghers syndrome].

An advanced small bowel mucinous adenocarcinoma with Peutz-Jeghers syndrome was resected, and we started capecitabine plus oxaliplatin (CapeOX) as adjuvant therapy. However, local recurrence was noted, and the tumor increased even after CapeOX plus bevacizumab and fluorouracil plus leucovorin plus irinotecan plus panitumumab (FOLFIRI plus panitumumab). Pembrolizumab was administered after confirming high-frequency microsatellite instability, and the tumor shrank markedly and remained shrunk for 20 months.

Renal denervation prevents myocardial structural remodeling and arrhythmogenicity in a chronic kidney disease rabbit model.

BACKGROUND: The electrophysiological (EP) effects and safety of renal artery denervation (RDN) in chronic kidney disease (CKD) are unclear. OBJECTIVE: The purpose of this study was to investigate the arrhythmogenicity of RDN in a rabbit model of CKD. METHODS: Eighteen New Zealand white rabbits were randomized to control (n = 6), CKD (n = 6), and CKD-RDN (n = 6) groups. A 5/6 nephrectomy was selected for the CKD model. RDN was applied in the CKD-RDN group. All rabbits underwent cardiac EP studies for evaluation. Immunohistochemistry, myocardial fibrosis, and renal catecholamine levels were evaluated. RESULTS: The CKD group (34.8% ± 9.2%) had a significantly higher ventricular arrhythmia (VA) inducibility than the control (8.6% ± 3.8%; P <.01) and CKD-RDN (19.5% ± 6.3%; P = .01) groups. In the CKD-RDN group, ventricular fibrosis was significantly decreased compared to the CKD group (7.4% ± 2.0 % vs 10.4% ± 3.7%; P = .02). Sympathetic innervation in the CKD group was significantly increased compared to the control and CKD-RDN groups [left ventricle: 4.1 ± 1.8 vs 0.8 ± 0.5 (102 µm2/mm2), P <.01; 4.1 ± 1.8 vs 0.9± 0.6 (102 µm2/mm2), P <.01; right ventricle: 3.6 ± 1.0 vs 1.0 ± 0.4 (102 µm2/mm2), P <.01; 3.6 ± 1.0 vs 1.0 ± 0.5 (102 µm2/mm2), P <.01]. CONCLUSION: Neuromodulation by RDN demonstrated protective effects with less structural and electrical remodeling, leading to attenuated VAs. In a rabbit model of CKD, RDN plays a therapeutic role by lowering the risk of VA caused by autonomic dysfunction.

Associations of the Prognostic Nutritional Index with the Cardiac Function and Survival after Cardiac Resynchronization Therapy.

Objective The relationship between changes in the nutritional status after cardiac resynchronization therapy (CRT) and the prognosis has not been fully elucidated. We aimed to evaluate the changes in the nutritional status as assessed by the prognostic nutritional index (PNI) and their associations with the improvement in the cardiac function and subsequent clinical outcomes. Methods The study population consisted of 119 patients with a CRT-device. They were divided into 2 groups, based on whether their PNI had increased at 6 months after CRT-device implantation (positive ΔPNI group, n=73) or not (negative ΔPNI group, n=46). The left ventricular (LV) end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were measured before and six months after CRT-device implantation. We compared the changes in the cardiac function and prevalence of adverse events (re-hospitalization due to worsening heart failure or all cause death) between the two groups. Results In the positive ΔPNI group, the LVEDV (186±93 mL vs. 149±71 mL, p<0.05) and LVESV (134±75 mL vs. 98±62 mL, p<0.05) were significantly decreased 6 months after CRT-device implantation. In addition, the LVEF (31±11% vs. 37±12%, p<0.05) was significantly increased after CRT-device implantation. In the negative ΔPNI group, no significant changes were observed in any echocardiographic parameters. During a median follow-up period of 914 days, there were 67 (56.3%) adverse events. In the Kaplan-Meier analysis, the positive ΔPNI group was associated with a lower risk of adverse events than the negative ΔPNI group (50.6% vs. 65.2%, log-rank p=0.042). Conclusion Our results suggest that improvement in the cardiac function after CRT-device implantation is associated with increases in the PNI, resulting in favorable outcomes.

High-resolution mapping of pulmonary vein potentials improved the successful pulmonary vein isolation using small electrodes and inter-electrode spacing catheter.

BACKGROUND: Intracardiac electrogram recording is influenced by the electrode size and inter-electrode spacing. Smaller electrodes with a closer inter-electrode spacing may improve the mapping resolution and outcome. METHODS: Substrate mapping of the left atrium and residual pulmonary vein (PV) potentials during sinus rhythm was sequentially performed using a 3.5-mm electrode tip catheter and a 1-mm electrode multielectrode catheter in 33 patients (Group 1) that underwent repeat atrial fibrillation (AF) procedures. PV gap identification and electrophysiological characteristics were compared. Arrhythmia freedom was compared with a propensity matched (1:2) control group (66 patients, Group 2) undergoing repeat AF procedures guided by wide inter-electrode spacing catheter. RESULTS: In the Group 1 patients, the total area of residual PV potentials measured using the 1-mm catheter was larger than that measured by the 3.5-mm catheter. Overall 1.97 ±â€¯0.59 (1-3) and 1.49 ±â€¯0.62 (1-3) PVs were identified by the 1-mm electrode and 3.5 mm catheters, respectively (P = 0.02). The gaps not identified by the 3.5 mm catheter had a smaller width and lower voltage. Radiofrequency catheter ablation in the areas with residual PV potentials identified by the 1-mm catheter resulted in complete electrical isolation of the PVs. Arrhythmia freedom at one year of follow-up was achieved in 26 of 33 (78.8%) patients in Group 1, which was significantly higher than the matched control group (33/66 [50%], P < 0.05). CONCLUSION: In the patients with a previous PV isolation, mapping with small, closely spaced electrodes can increase the detection rate of residual PV potentials and improve the outcome.

Cigarette smoking causes a worse long-term outcome in persistent atrial fibrillation following catheter ablation.

INTRODUCTION: Cigarette smoking contributes to the development of atrial fibrosis via nicotine. The impact of smoking on ablation results in persistent atrial fibrillation (AF) is unknown. We aimed to investigate the triggers and long-term outcome between smokers and nonsmokers in the patients with persistent AF after catheter ablation. METHODS: This study included 201 (177 males, 53 ± 10 years old) patients who received index catheter ablation, including pulmonary vein isolation (PVI) and complex fractionated atrial electrograms (CFAEs) ablation for persistent AF, retrospectively. Electrophysiological characteristics at the index procedure and long-term outcome were investigated to determine the differences between smokers and nonsmokers. RESULTS: Baseline characteristics were similar between two groups. Pulmonary vein (PV) triggers were found in all patients in the two groups. There was a higher incidence of nonpulmonary vein (NPV) triggers in smokers than in nonsmokers (61% vs. 31%, P < 0.05). There were no differences of the long-term ablation outcomes between smokers and nonsmokers in Kaplan-Meier analysis. Smokers with PV plus right atrial NPV (RA-NPV) triggers had a higher incidence of recurrence (log-rank P < 0.05) than those without RA-NPV triggers, but not in nonsmokers, after a mean follow-up of 31 ± 25 months. CONCLUSIONS: Smoking increases the incidence of NPV triggers in patients with persistent AF. Smokers who have RA-NPV triggers during index procedure do have a worse outcome after catheter ablation, indicating the harmful effects of nicotine to right atrium.

Heterogeneous distribution of substrates between the endocardium and epicardium promotes ventricular fibrillation in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Aims: Whether the distribution of scar in arrhythmogenic right ventricular cardiomyopathy (ARVC) plays a role in predicting different types of ventricular arrhythmias is unknown. This study aimed to investigate the prognostic value of scar distribution in patients with ARVC. Methods and results: We studied 80 consecutive ARVC patients (46 men, mean age 47 ± 15 years) who underwent an electrophysiological study with ablation. Thirty-four patients receive both endocardial and epicardial mapping. Abnormal endocardial substrates and epicardial substrates were characterized. Three groups were defined according to the epicardial and endocardial scar gradient (<10%: transmural, 10-20%: intermediate, >20%: horizontal, as groups 1, 2, and 3, respectively). Sinus rhythm electrograms underwent a Hilbert-Huang spectral analysis and were displayed as 3D Simultaneous Amplitude Frequency Electrogram Transformation (SAFE-T) maps, which represented the arrhythmogenic potentials. The baseline characteristics were similar between the three groups. Group 3 patients had a higher incidence of fatal ventricular arrhythmias requiring defibrillation and cardiac arrest during the initial presentation despite having fewer premature ventricular complexes. A larger area of arrhythmogenic potentials in the epicardium was observed in patients with horizontal scar. The epicardial-endocardial scar gradient was independently associated with the occurrence of fatal ventricular arrhythmias after a multivariate adjustment. The total, ventricular tachycardia, and VF recurrent rates were higher in Group 3 during 38 ± 21 months of follow-up. Conclusion: For ARVC, the epicardial substrate that extended in the horizontal plane rather than transmurally provided the arrhythmogenic substrate for a fatal ventricular arrhythmia circuit.

Novel electrophysiological criteria for septal ventricular outflow tract tachycardias requiring a sequential bilateral ablation.

BACKGROUND: Septal ventricular outflow tract ventricular arrhythmias (OT-VAs) are defined as septal origin VAs from the right ventricular or left ventricular OT. Patients with septal OT-VAs may require a sequential bilateral OT ablation. This study aimed to evaluate the electrophysiological characteristics and ablation outcome in patients with septal OT-VAs. METHODS: We retrospectively analyzed the electrocardiography and electrophysiological parameters in 96 patients (mean age 49 ± 15 years, 49 male) undergoing bilateral activation mapping before catheter ablation of idiopathic septal OT-VAs. The patients were categorized into three groups based on the successful ablation sites, including the right ventricular outflow tract (RVOT), RVOT/left ventricular outflow tract (LVOT), and LVOT. RESULTS: Mapping in the three groups demonstrated a gradually decreasing and increasing trend in the earliest activation time obtained from the RVOT and LVOT, respectively. The absolute earliest activation time discrepancy (AEAD) of ≤18 milliseconds could predict the requirement for a sequential bilateral ablation with a sensitivity and specificity of 100.0% and 93.7%, respectively. The small AEAD (≤21 milliseconds) was associated with a higher recurrence rate in patients receiving a successful unilateral ablation, while patients with a longer distance between the bilateral OT earliest activation sites (DEA > 26 mm) increased future recurrences after an initially successful sequential bilateral ablation. CONCLUSIONS: The application of bilateral OT-VA activation mapping and the measurement of the AEAD and DEA provided not only pivotal information for the ablation strategy, but also prognostic implications for recurrences in patients with septal OT-VAs.

Aortic Aneurysm-associated Disseminated Intravascular Coagulation that Responded Well to a Switch from Warfarin to Rivaroxaban.

We describe a case in which uncontrolled chronic disseminated intravascular coagulation (DIC) caused by an aortic aneurysm that was exacerbated by chemotherapy for lung cancer, showed dramatic improvement when warfarin, which was being administered for atrial fibrillation, was replaced by rivaroxaban, a direct oral anticoagulant (DOAC). The present case is interesting because a DOAC was effective in treating DIC due to an aortic aneurysm, whereas warfarin, another oral anticoagulant, was ineffective. In controlling DIC, it is important to inhibit activated coagulation factors such as thrombin and activated factor X, rather than the coagulation factors, which act as substrates.

Novel electrocardiogram and electrophysiological findings for differentiating idiopathic left posterior papillary muscle and left posterior fascicular ventricular arrhythmias.

PURPOSE: Differentiation between idiopathic left posterior fascicular ventricular arrhythmias (LPF-VAs) and posterior papillary muscle (PPM) VAs is of clinical value. This study aimed to develop an algorithm to distinguish PPM-VAs from LPF-VAs. METHODS: This study enrolled 73 consecutive cases, including 31 with PPM-VAs and 42 with LPF-VAs, undergoing successful ablation by using 3D mapping and intracardiac echography to confirm the origin of the VAs. Electrocardiographic and electrophysiological parameters were compared between two groups. RESULTS: The 12-lead electrocardiography of the PPM-VAs was characterized by a longer QRS duration than that in LPF-VAs (154.4 ± 14.5 vs. 132.3 ± 13.1 ms, P < 0.001). A QRS duration ≥133 ms was observed in all patients (100%) with PPM-VAs and 13/42 (31.0%) patients with LPF-VAs. The conduction duration from the earliest left ventricular activation site of the VA to the proximal right bundle branch (VA-RBB) was longer in patients with PPM-VAs than LPF-VAs (51.3 ± 12.2 vs. 23.6 ± 7.7 ms, P < 0.001). Based on the ROC analysis, a VA-RBB >36 ms was recognized in 28/31 patients with PPM-VAs (90.3%) and 2/42 with LPF-VAs (4.8%). An algorithm incorporating a QRS duration of ≥133 ms with a conduction duration of a VA-RBB of >36 ms could yield a sensitivity of 90.3% and specificity of 100% for discriminating PPM-VAs from LPF-VAs. CONCLUSIONS: The novel algorithm incorporating a QRS duration of ≥133 ms with a conduction duration of the VA-RBB of >36 ms could be useful in differentiating PPM-VAs from LPF-VAs.

The use of a novel signal analysis to identify the origin of idiopathic right ventricular outflow tract ventricular tachycardia during sinus rhythm: Simultaneous amplitude frequency electrogram transformation mapping.

INTRODUCTION: The signal characteristics of intracardiac bipolar electrograms at the origin of idiopathic RVOT-VT during sinus rhythm remain unclear. OBJECTIVE: The study sought to develop a novel real-time/online technique, simultaneous amplitude frequency electrogram transformation (SAFE-T), to quantify and localize the diseased ventricular substrate in idiopathic RVOT-VT. METHODS: We retrospectively investigated the intracardiac bipolar recordings in 70 consecutive patients (26% male, mean age 42±12 years) who underwent successful radiofrequency catheter ablation of idiopathic RVOT-VT. We quantified the extent of the frequency fraction of ventricular potentials during sinus rhythm or ventricular pacing using a novel formula, the product of instantaneous amplitude and frequency, and showed that in a 3D geometry as an online SAFE-T map. RESULTS: The characteristics of the HHT spectra of electrograms derived from VT origins demonstrated high frequency components (>70 Hz), which were independent of the rhythm. The density of the abnormal potentials at the VT origins were higher (VT origins, 7.5±2.3 sites/cm2 vs. surrounding myocardium, 1.5±1.3 sites/cm2, p<0.001), and were significantly decreased after ablation (0.7±0.6 sites/cm2, p<0.001). A small region of abnormal potentials were observed in the VT origins (mean area of 1.5±0.8 cm2). The SAFE-T maps predicted the VT origins with 92% sensitivity, 78% specificity with optimal cut-off value of >3.0 Hz·mV. CONCLUSION: The online SAFE-T map was feasible for quantifying the diseased ventricular substrate, irrespective of the rhythm of activation, and can be used to identify the optimal ablation targets for idiopathic RVOT-VT. We found a limited region of abnormal potentials where the RVOT-VT origins were successfully ablated.

A novel method to enhance phenotype, epicardial functional substrates, and ventricular tachyarrhythmias in Brugada syndrome.

BACKGROUND: Fever is associated with the manifestation of Brugada phenotype and ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with Brugada syndrome (BrS). The thermal effect on the pathogenesis of functional substrates in BrS remains unknown. OBJECTIVE: This study aimed to elucidate the thermal effect on BrS phenotype, VT/VF, and electrophysiological characteristics of epicardial functional substrates in BrS. METHODS: We consecutively studied 15 patients with BrS receiving radiofrequency catheter ablation for drug-refractory ventricular tachyarrhythmias. Baseline characteristics, electrocardiographic features, and changes in epicardial functional substrates before and after epicardial warm water instillation (n = 6) were recorded and analyzed. RESULTS: A total of 15 male patients (mean age 41.3 ± 10.3 years) with type 1 BrS presenting with ventricular tachyarrhythmias were consecutively enrolled. Epicardial mapping in 11 patients demonstrated a significantly larger epicardial scar/low-voltage zone (LVZ) area within the right ventricular outflow tract and anterior right ventricular free wall than within the endocardium (6.32 ± 12.74 cm2 vs 52.91 ± 45.25 cm2; P = .007). Epicardial warm water instillation in 6 patients led to a significant enlargement of the functional scar/LVZ area (123.83 ± 35.26 cm2 vs 63.53 ± 40.57 cm2; P = .03), accelerated conduction velocity of the endocardium and epicardium without scar/LVZ area, and increased VT/VF inducibility (16.7% vs 100%; P = .02). Ablation by targeting premature ventricular complexes and/or epicardial abnormal substrates rendered noninducibility of VT/VF and prevented the recurrences of VT/VF. CONCLUSION: Epicardial warm water instillation enhanced functional epicardial substrates, which contributed to the increased inducibility of ventricular tachyarrhythmias in BrS. Ablation by targeting the triggers and abnormal epicardial substrates provided an effective strategy for preventing ventricular tachyarrhythmia recurrences in BrS.

Left Atrial Size and Left Ventricular End-Systolic Dimension Predict the Progression of Paroxysmal Atrial Fibrillation After Catheter Ablation.

INTRODUCTION: Although rare, some paroxysmal atrial fibrillations (AF) still progress despite radiofrequency (RF) ablation. In the study, we evaluated the long-term efficacy of RF ablation and the predictors of AF progression. METHODS: A total of 589 paroxysmal AF patients (404 men and 185 women; aged 54 ± 12 years) who received 3-dimensional mapping and ablation were enrolled. Their clinical parameters and electrophysiological characteristics were collected. They were divided into Group 1 (N = 13, with AF progression) and Group 2 (N = 576, no AF progression). AF progression was defined as recurrence of persistent AF. RESULTS: Group 1 patients had larger left atrial (LA) diameter, larger left ventricle (LV) end-systolic and end-diastolic diameters, poorer LV systolic function, and more amiodarone use at baseline. After 1.2 ± 0.5 procedures, 123 (21%) patients experienced recurrence during 56 ± 29 months' follow-up. In the multivariate analysis, LA diameter (P = 0.018, HR = 1.12, 95% CI = 1.02-1.24) and LV end-systolic diameter (P = 0.005, HR = 1.10, 95% CI = 1.03-1.17) independently predicted AF progression. LA diameter >43 mm and LV end-systolic diameter >31 mm were the best cut-off values for predicting AF progression by ROC analysis. AF progression rate achieved 19% if they had both larger LA diameter (>43 mm) and LV end-systolic diameter (>31 mm). CONCLUSION: RF ablation prevents the progression of paroxysmal AF effectively, except in patients with increased LA diameter and LV end-systolic diameter on echocardiogram, suggesting more aggressive rhythm control therapies should be considered in these patients.

Association of Serum n-3/n-6 Polyunsaturated Fatty Acid Ratio With T-Wave Alternans in Patients With Ischemic Heart Disease.

Several studies have demonstrated that oral intake of n-3 polyunsaturated fatty acids, specifically eicosapentaenoic acid (EPA), prevents ventricular tachyarrhythmias (VT) with ischemic heart disease, but the underlying mechanisms still remain unclear. Thus, we examined the relation between the serum EPA/arachidonic acid (AA) ratio and electrophysiological properties in patients with ischemic heart disease. The study subjects consisted of 57 patients (46 males, mean age, 66 ± 13 years) with ischemic heart disease. T-wave alternans (TWA) and heart rate variability were assessed by 24hour Holter ECG, and left ventricular ejection fraction (LVEF) was determined by echocardiography. Fasting blood samples were collected, and the serum EPA/AA ratio was determined. Based on a median value of the serum EPA/AA ratio, all subjects were divided into two groups: serum EPA/AA ratio below 0.33 (Group-L, n = 28) or not (Group-H, n = 29). We compared these parameters between the two groups. LVEF was not different between the two groups. The maximum value of TWA was significantly higher in Group-L than in Group-H (69.5 ± 22.8 µV versus 48.7 ± 12.0 µV, P = 0.007). In addition, VT defined as above 3 beats was observed in 7 cases (25%) in Group-L, but there were no cases of VT in Group-H (P = 0.004). However, low-frequency (LF) component, high-frequency (HF) component, LF to HF ratio, and standard deviation of all R-R intervals were not different between the two groups. These results suggest that a low EPA/AA ratio may induce cardiac electrical instability, but not autonomic nervous imbalance, associated with VT in patients with ischemic heart disease.

[The association of hypocarnitinemia with enteral diets and antiepileptic drugs in children and adults with severe physical and mental disabilities].

OBJECTIVE: To examine the risk factors of hypocarnitinemia and hypocarnitinemic symptoms in children and adults with severe physical and mental disabilities. METHODS: The status of hypocarnitinemia as well as the related symptoms were assessed in a total of 78 children and adults with severe physical and mental disabilities who were admitted to National Hospital Organization Iou National Hospital. Their enteral diets and the medication of antiepileptic drugs were evaluated. RESULTS: Markedly decreased blood carnitine levels were noted in patients undergoing an enteral diet without carnitine supplementation as well as in those receiving a combination of valproate sodium (VPA) and phenobarbital (PB). These hypocarnitinemic patients tended to have more frequent episodes of hypoglycemia and hyperammonemia. CONCLUSIONS: Supplemental L-carnitine is needed in patients receiving an enteral diet free of carnitine, those with combination therapy of VPA and PB under oral feeding conditions, and those who develop hyperammonemia during VPA therapy. Patients who received a carnitine-supplemented enteral diet maintained their serum carnitine levels with a relatively low supplemental dose of carnitine.

Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model.

Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor ß1 (TGF-ß1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-ß1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.

Isolation and molecular characterization of single-chain Fv antibodies raised against pollen allergens from Japanese cedar (Cryptomeria japonica D. Don).

We report here the isolation and molecular characterization of single-chain Fv (scFv) antibodies raised against two major allergens, Cryj1 and Cryj2, in the pollen of Cryptomeria japonica by the phage display method. Recombinant phages that produced scFv antibodies that bound to Cryj1 or Cryj2 were isolated by selection with immobilized antigens in microtiter plates. After selection of six Cryj1- and four Cryj2-specific scFv antibodies with strong binding activity, we performed pairwise interaction analysis of them by surface plasmon resonance. The analysis revealed that the scFv antibodies against Cryj1 bound to only four non-overlapping epitopes, with dissociation constants that ranged from 4.84x10(-9) M to 1.62x10(-7) M. By contrast, four Cryj2-specific scFv antibodies inhibited each other's binding to Cryj2, with dissociation constants from 1.11x10(-7) M to 4.21x10(-7) M. Our results indicate that recombinant technology provides a time-saving method for the production of antibodies against pollen allergens.

Lymphoma with large-plaque parapsoriasis treated with PUVA.

We report on a 78-year-old Japanese woman with a 50-year history of large-plaque parapsoriasis that had evolved into cutaneous T-cell lymphoma. Her large-plaque parapsoriasis had been treated with psoralen plus ultraviolet A for 10 years. Subsequently an isolated nodule appeared on her right lower leg. Prior or concurrent patches or plaques were absent. Histology revealed a diffuse nonepidermotropic infiltrate of large lymphocytes in the dermis, which had enlarged nuclei and prominent nucleoli. A diagnosis of CD30- cutaneous large T-cell lymphoma was made. Following systemic chemotherapy, there was clinical improvement. No evidence of recurrence or systemic lymphoma has subsequently been found.