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AIM No flow-limiting dissection after drug-coated balloon (DCB) treatment for femoropopliteal (FP) lesions is considered as one of the endpoints, but it has not investigated the difference between each vessel dissection. This study aimed to clarify whether there is a difference between no dissection and type C dissection without flow-limiting dissection for 3 months by peak systolic velocity ratio (PSVR) based on duplex ultrasonography. METHODS Between February 2020 and April 2021, 44 consecutive de novo FP diseases that underwent endovascular therapy (EVT) with DCB were enrolled in this study. 65.9% of the patients had intermittent claudication, and mean lesion lengths were 194±107 mm. The chronic total occlusion was 38.6%. After DCB treatment, vessel dissection pattern was categorized by angiography. The minimum lumen area (MLA) identified by intravascular ultrasound was serially evaluated with PSVRs at 1 day, 1 month, and 3 months after EVT. RESULT All lesions were treated with DCB without provisional stents. The vessel dissection pattern after DCB treatment showed that types D, E, and F were not observed, 9% were no dissection, 27% were type A, 32% were type B, and 32% were type C. In all cases, the PSVR values of MLA site were less than 2.6 at 3 months, and there were no significant differences between no dissection and type C dissection. CONCLUSION Up to dissection pattern "C" is considered acceptable as one of the endpoints to determine the need for provisional stenting after DCB treatment.

Imaging modalities have developed to provide precise information in the assessment of lower extremity artery disease (LEAD), including both quantitative measurements and morphological assessment. However, a lack of standardization for the evaluation methods introduces inconsistency and potential risk. This consensus document from Japan Endovascular Treatment Conference (JET) summarizes the methods of measurement and assessment of intravascular ultrasound (IVUS), optical frequency domain imaging (OFDI), and angioscopy. We propose standardized approaches for the evaluation of these modalities in endovascular therapy (EVT).

Drug-coated balloon (DCB) is now available for endovascular treatment (EVT) of superficial femoral arteries (SFA). Although it has been reported that severe vessel dissection after balloon angioplasty was risk of restenosis, it is difficult to predict the vessel dissection patterns before balloon angioplasty. We investigated the correlation between plaque morphology and vessel dissection pattern after balloon angioplasty using the intravascular ultrasound (IVUS). A total of 73 de novo SFA lesions were enrolled in this study. IVUS examinations were measured at the minimum lumen area in the control angiogram. Plaque morphology, minimum lumen area (MLA) and vessel diameter at the same point were evaluated before and after the initial balloon angioplasty. Vessel dissection patterns after the initial balloon angioplasty were classified into 7 types (A to F). There were no severe dissection patterns which were more than type D dissection in this study. All patients were treated with DCB without any bailout stenting. No dissection was found in 35.6% (26/73). Type A, B and C dissections were seen in 17.8% (13/73), 40% (27/73) and 9.6% (7/73), respectively. Although there were no relations between plaque morphology and vessel dissection patterns (p = 0.547), the MLA with dissection was larger than that without dissection (5.78 mm2 versus 4.63 mm2, p = 0.032). Although the dissection patterns could not be predicted in non-severe (Non or A to C) dissection, our result might suggest that IVUS image has the potential to reduce severe dissection.

This paper presents the effects of being hugged by a robot to encourage prosocial behaviors. In human-human interaction, touches including hugs are essential for communication with others. Touches also show interesting effects, including the “Midas touch,” which encourages prosocial behaviors from the people who have been touched. Previous research demonstrated that people who touched a robot experienced positive impressions of it without clarifying whether being hugged by a robot causes the Midas touch effect, i.e., positively influences engagement in prosocial behaviors. We developed a huge, teddy-bear-like robot that can give reciprocal hugs to people and experimentally investigated its effects on their behaviors. In the experiment, a robot first asked participants to give a hug and then asked them to make charitable donations in two conditions: with or without a reciprocated hug. Our experiment results with 38 participants showed that those who were hugged by a robot donated more money than those who only hugged the robot, i.e., without a reciprocated hug.

The gene encoding a transmembrane glycoprotein LIG-1, of which the extracellular region was organized with the leucine-rich repeats and immunoglobulin-like domains, was disrupted in mice by gene targeting. LIG-1-deficient mice developed a skin change on the tail and facial area after birth. The affected skin was histologically reminiscent of the epidermis in human common skin disease ‘psoriasis’. LIG-1 was expressed in basal cells of the epidermis and outer root sheath cells of hair follicles in mice. Interestingly, the LIG-1 expression was apparently down-regulated in the psoriatic lesions, suggesting that LIG-1 inversely correlates with proliferative ability of epidermal keratinocytes.

The relationship between CD4(+) T cell-mediated airway eosinophilic inflammation and bronchial hyper-responsiveness (BHR) was investigated. Ovalbumin-reactive T(h)0 clones were adoptively transferred to unprimed BALB/c mice and then the mice were challenged by inhalation of the relevant antigen. Upon antigen provocation, infused T(h) clones infiltrated into the airways, followed by the accumulation and degranulation of eosinophils, goblet cell hyperplasia, edema and increase in bronchial responsiveness to acetylcholine. Transfer of several clones that differed in the levels of IL-5 production revealed that the magnitude of in vivo eosinophilia strongly correlated with the IL-5-producing capacity of the infused T(h) clones. Administration of anti-IL-5 mAb almost completely suppressed antigen-induced eosinophilic inflammation and BHR. Administration of anti-IL-4 mAb or anti-IFN-gamma mAb enhanced the eosinophilia and BHR, whereas anti-IL-2 mAb did not affect them. The number of accumulated eosinophils significantly correlated with the intensity of BHR. Our present results clearly demonstrated that CD4(+) T cells induced BHR as a result of eosinophilic inflammation. IL-5 totally regulated both responses.

1. To delineate the mechanism by which cyclic AMP (cAMP) suppresses interleukin (IL)-5 synthesis, the effects of prostaglandin (PG) E2, forskolin, dibutyryl (db)-cAMP and the Ca2+ ionophore, ionomycin on cytokine synthesis, proliferation and CD25 expression of human T cells were investigated. Further studies were performed by measurement of the intracellular concentrations of cyclic AMP ([cAMP]i) and Ca2+ ([Ca2+]i) and by electrophoretic mobility shift analysis (EMSA). 2. PGE2, forskolin and db-cAMP suppressed IL-5 production by human T cell line following T cell receptor (TCR)-stimulation. PGE2 suppressed TCR-induced messenger RNA (mRNA) expression of IL-2, IL-4 and IL-5, as well as proliferation and CD25 expression. 3. Cyclic AMP-mediated suppression of cytokine synthesis, proliferation and CD25 expression in human T cells were attenuated by ionomycin. 4. [cAMP]i was increased by PGE2 and forskolin. PGE2 suppressed the TCR-induced biphasic increase in [Ca2+]i. EMSA revealed that four specific protein-DNA binding complexes related to NF-AT were detected at the IL-5 promoter sequence located from -119 to -90 relative to the transcription initiation site. The slowest migrating complex induced by TCR stimulation was enhanced by PGE2 and further upregulated by ionomycin. Another binding which did not compete with cold AP-1 oligonucleotides, was constitutively present and was unaffected by PGE2 but enhanced by ionomycin. 5. The suppressive effect of cyclic AMP on human IL-5 synthesis is mediated by interference with intracellular Ca2+ mobilization but distinct from the NF-AT-related pathway.

1 We have recently demonstrated that airway eosinophilic inflammation can be transferred to unprimed mice by infusing interleukin (IL)-5-producing T cell clones. Using that murine model, we performed this study to delineate the mechanism of cyclosporin A and dexamethasone to inhibit allergic airway eosinophilic inflammation. 2 The ovalbumin-reactive murine T cell clones, FJ17, produced IL-2, IL-4 and IL-5 upon stimulation with relevant antigen. In FJ17-transferred mice, messenger RNA (mRNA) of IL-2 and IL-5 expressed in the lungs, the number of eosinophils in bronchoalveolar lavage fluid (BALF) was increased and the bronchial responsiveness to acetylcholine was enhanced after antigen provocation. 3 Cyclosporin A (10, 100 ng ml−1) and dexamethasone (10, 100 ng ml−1 suppressed the production of IL-5 as well as IL-2 and IL-4 by FJ17 in vitro. 4 Subcutaneously administered cyclosporin A (30 mg kg−1) and dexamethasone (10 mg kg−1) inhibited antigen-induced mRNA expression of IL-2 and IL-5, increase of BALF eosinophils and bronchial hyperresponsiveness of FJ17-transferred mice in vivo. The number of BALF eosinophils was correlated with the bronchial responsiveness to acetylcholine (r = 0.672). 5 The results clearly indicated that the suppression of IL-5 synthesis by T cells is involved in the effects of cyclosporin A and dexamethasone to inhibit allergic airway eosinophilic inflammation. British Journal of Pharmacology (1998) 124, 1425–1432; doi:10.1038/sj.bjp.0701982

Background: The Lewis rat among highly inbred strains exhibits significant airway hyperresponsiveness (AHR) following intravenous administration of Sephadex G-200 (Sephadex). The aim of this study was to investigate the association of Sephadex-induced AHR with changes in airway inflammation in Lewis rats. Methods: A suspension (0.5 mg/ml/rat) of Sephadex was intravenously administered to male Lewis rats on days 0, 2 and 5. Measurement of airway responsiveness to serotonin, bronchoalveolar lavage (BAL) and histological study were performed on day 2–11. Results: Significant AHR induced by Sephadex was recognized on day 2 (p < 0.05), and AHR reached a maximum on day 7 (p < 0.001). In the BAL study, eosinophils increased on day 2 (p < 0.01) with a peak on day 5 (p < 0.05). In the histological study, we found Sephadex beads trapped in small arteries of the lung and granulomatous arteritis on day 2 or later. Pulmonary granulomas, horseshoe-shaped multinuclear giant cells, eosinophils and goblet cell hyperplasia were observed on day 2, and the degree became intense on day 5–7. GCC-AP0341 (10 mg/kg, i.p. × 3) inhibited the recruitment of eosinophils in BAL fluid and in lung tissue, but it did not inhibit AHR. The compound also inhibited pulmonary granulomas and goblet cell hyperplasia. Conclusion: The mechanism of Sephadex-induced AHR may not be directly associated with inflammatory changes such as recruitment of eosinophils, pulmonary granulomas and hyperplasia of goblet cells in rats.

Bronchial asthma is characterized by chronic eosinophilic inflammation of the bronchial mucosa. Accumulating evidences suggest that activated T cells and T cell cytokines play critical roles in the local accumulation and activation of eosinophils. To further delineate the critical role of T cells on asthma, we tested the possibility whether eosinophilic inflammation of the bronchial mucosa is induced by transferred T cell clones, in the absence of antigen-specific immunoglobulins (IgE, A, and G). Ovalbumin-specific Th2 clones were established and cytokine profiles were determined. Eosinophilic inflammation accompanied with airway hyperresponsiveness occurred only when unprimed mice were transferred with IL-5 producing Th2 clones and challenged by the inhalation of relevant antigen. Increase of IL-5 concentration in bronchoalveolar lavage fluid (BALF) was detected after the challenge, indicating the local production of cytokines by the transferred T cells, and preceded the appearance of the airway eosinophilia. Eosinophil infiltration was completely suppressed by the administration of anti-IL-5 neutralizing antibody, indicating the essential role of IL-5 in this model. The intensity of the eosinophil accumulation in vivo correlated well with the capacity of the T cell clones to produce IL-5 in vitro. We concluded that the existence of IL-5-producing helper T cells is sufficient for the development of the eosinophilic inflammation at the bronchial mucosa upon inhalation challenge of the relevant antigen.

We investigated whether somatostatin modulates the generation of long-term potentiation (LTP) in rat perforant path-dentate gyrus synapse in vivo. When somatostatin was injected intracerebroventricularly (i.c.v.) 20 min prior to the tetanus, the intensity of LTP increased dose dependently. Synaptic potential evoked by a low-frequency test stimulation, however, was not altered by somatostatin. We next tested whether the LTP-augmenting effect of somatostatin is mediated by cholinergic activation, because somatostatin was demonstrated to promote acetylcholine release in rat hippocampal slice. Pirenzepine (50 nmol/rat), a muscarinic M 1 receptor antagonist, did not affect the tetanus-induced LTP by itself. But when it was co-applicated with the somatostatin (50 ng/rat) 20 min before tetanus, it completely abolished the LTP-augmenting effect of somatostatin. Then we examined the effect of octreotide, a potent agonist specifically binding to somatostatin receptor subtypes 2 and 4, on the generation of LTP. Octreotide (500 ng/rat) also facilitated the intensity of LTP. These results suggest that somatostatin facilitates the generation of perforant path-dentate gyrus granule cell LTP by activating the muscarinic cholinergic receptor and the effect of somatostatin is induced, at least partly, by somatostatin receptor subtypes 2 and 4 in vivo.

Background: Carbon dioxide (CO2) has been used as an arterial contrast agent for high-risk patients who were allergic to iodinated contrast material and for those with chronic kidney disease (CKD). The feasibility, safety, imaging quality and therapeutic role of CO2 angiography in the endovascular therapy (EVT) for patients with CKD was evaluated. Methods and Results: EVT was performed in 107 consecutive patients with iliofemoral artery disease (148 limbs; mean age, 73±9 years) who were admitted to our hospital from January 2010 to April 2011. Intravascular ultrasound (IVUS)-guided EVT with CO2 was applied for the treatment of 50 patients (70 limbs) with CKD (group 1). IVUS-guided EVT with iodinated contrast media was applied for the treatment of 57 patients (78 limbs) without CKD (group 2). CO2 was injected by hand using a simple homemade delivery system. The overall technical success was 100% in both groups without any major complication. Preprocedure and postprocedure ankle-brachial indices significantly improved in the both groups (0.93±0.11 vs. 0.59±0.19, P

Background: The crucial role of T helper (Th) 2 cells in allergic eosinophilic inflammation has been established. Methods: To determine the dynamics of Th2 cells in airway eosinophilic inflammation, ovalbumin-reactive murine Th2 clones were infused into unprimed mice. Results: The infused T cells were activated and migrated into the bronchial submucosa upon provocation with the relevant inhaled antigen. The T cell migration was followed by massive eosinophilic infiltration, edema, swelling of epithelial cells in the lung and a significant increase in bronchial responsiveness to acetylcholine. Conclusion: Clonal Th2 cells have the potential to accumulate and induce eosinophilic inflammation in the lung upon antigenic stimulation.

Cysteamine has been reported to disturb learning performance in rats. Our study was made to determine if this is also true in mice. Adult male ddY mice were subjected to a battery of learning tests following our standard experimental protocols. Cysteamine injected 30 min prior to the learning trial dose-dependently increased the number of errors in the testing trial of step-down test, and its effect was statistically significant at a dose of 200 mg/kg. In the lever press test, 200 mg/kg injection of cysteamine also suppressed the conditioned avoidance rate. However, no significant changes were observed in other tests. These results suggest that the learning disorder induced by cysteamine in mice is restricted to a specific type of behavioral performance. In conclusion, the mechanism by which cysteamine generates learning deficiency in mice may differ from that in rats.

A novel series of 1-pyridylisoquinoline and 1-pyridyldihydroisoquinoline derivatives has been prepared. These compounds showed potent PDE4 inhibitory activities and a broad margin between the K(i) value of the rolipram binding affinity and the IC(50) value of PDE4 inhibition. They also exhibited potent inhibitory activities toward LPS-induced TNF-alpha production in mice.

The gene encoding a transmembrane glycoprotein LIG-1, of which the extracellular region was organized with the leucine-rich repeats and immunoglobulin-like domains, was disrupted in mice by gene targeting. LIG-1-deficient mice developed a skin change on the tail and facial area after birth. The affected skin was histologically reminiscent of the epidermis in human common skin disease 'psoriasis'. LIG-1 was expressed in basal cells of the epidermis and outer root sheath cells of hair follicles in mice. Interestingly, the LIG-1 expression was apparently down-regulated in the psoriatic lesions, suggesting that LIG-1 inversely correlates with proliferative ability of epidermal keratinocytes.

SUMMARYEven though the existence of phosphodiesterase (PDE) 7 in T cells has been proved, the lack of a selective PDE7 inhibitor has confounded an accurate assessment of PDE7 function in such cells. In order to elucidate the role of PDE7 in human T cell function, the effects of two PDE inhibitors on PDE7A activity, cytokine synthesis, proliferation and CD25 expression of human peripheral blood mononuclear cells (PBMC) were determined. Recombinant human PDE7A was obtained and subjected to cyclic AMP-hydrolysis assay. PBMC of Dermatophagoides farinae mite extract (Df)-sensitive donors were stimulated with the relevant antigen or an anti-CD3 monoclonal antibody (MoAb). PBMC produced IL-5 and proliferated in response to stimulation with Df, while stimulation with anti-CD3 MoAb induced CD25 expression and messenger RNA (mRNA) synthesis of IL-2, IL-4 and IL-5 in peripheral T cells. A PDE inhibitor, T-2585, which suppressed PDE4 isoenzyme with high potency (IC50 = 0·00013 μm) and PDE7A with low potency (IC50 = 1·7 μm) inhibited cytokine synthesis, proliferation and CD25 expression in the dose range at which the drug suppressed PDE7A activity. A potent selective inhibitor of PDE4 (IC50 = 0·00031 μm), RP 73401, which did not effectively suppress PDE7A (IC50 > 10 μm), inhibited the Df- and anti-CD3 MoAb-stimulated responses only weakly, even at 10 μm. PDE7 may play a critical role in the regulation of human T cell function, and thereby selective PDE7 inhibitors have the potential to be used to treat immunological and inflammatory disorders.

Background: Helper T cells are involved in the pathophysiologic condition of asthma, so modulation of cytokine production may be effective therapy. Objective: We aimed to selectively control the synthesis of IL-5 by helper T cells and tested in vivo effects using a murine asthma model. Methods: The effect of dexamethasone, FK506, cyclosporin A, and nonactin (a macrolide compound produced by Streptomyces griseus ) on cytokine production by allergen-specific T-cell clones was determined. The effect of these agents and an anti-IL-5 neutralizing antibody on airway eosinophilic inflammation was investigated in a murine asthma model. Results: Dexamethasone, FK506, and cyclosporin A suppressed the production of IL-2, IL-4, and IL-5 by human helper T cells, which shows a similar concentration-response relationship in each case. Cyclosporin A and dexamethasone inhibited airway eosinophilia in vivo. Nonactin suppressed IL-5 synthesis but not IL-2 or IL-4 synthesis, and it also significantly suppressed airway eosinophilia. Conclusion: Nonactin only suppressed IL-5 synthesis and was as effective against eosinophilia as cyclosporin A and dexa-methasone, which indicates that IL-5 is a reasonable therapeutic target in allergic disorders that are accompanied by eosinophilic inflammation. (J Allergy Clin Immunol 2000;106:S58-64.)

Background: The essential role of Th cells and T cell cytokines in eosinophilic inflammation has been established. Methods: To determine whether Th cells are sufficient for the development of airway eosinophilic inflammation, ovalbumin–reactive murine Th clones were established and infused into unprimed mice. Results: Eosinophilic infiltration into the lung was induced upon antigen inhalation in parallel with the rise in bronchoalveolar lavage fluid (BALF) eosinophil peroxidase activity. Neither IgG, IgA, nor IgE antibodies were present in this model. Pathological examination showed swelling and desquamation of epithelial cells, mucous plugs, and goblet cell hyperplasia, all of which well resemble human asthma. Fluorescent probe labeled Th clones migrated into the lung prior to the eosinophil accumulation. Bronchial hyperresponsiveness (BHR) was clearly induced upon antigen inhalation. Anti–IL–5 monoclonal antibody abrogated the responses. Dexamethasone and cyclosporin A suppressed cytokine production by Th cells both in vitro and in vivo, BALF eosinophilia, and BHR. The number of eosinophils recovered in the BALF correlated with the intensity of BHR. Conclusion: The results clearly indicated that monoclonal Th cells are sufficient for the development of both airway eosinophilia and BHR. Agents capable of downregulating IL–5 production seem promising for the treatment of bronchial asthma.

We have recently demonstrated that airway eosinophilic inflammation can be transferred to unprimed mice by infusion of IL-5-producing T cell clones. In this study, we investigated the effects of dexamethasone and cyclosporin A on the airway eosinophilic inflammation in mice transferred with T cell clones. An ovalbumin-reactive T cell clone, KW29, produced IL-5 as well as IL-2 and IL-4 upon stimulation with relevant antigen. Dexamethasone and cyclosporin A dose-dependently suppressed the production of these cytokines in vitro. The number of eosinophils recovered in the bronchoalveolar lavage fluid and the airway responsiveness to acetylcholine were increased in KW29-transferred mice after antigen provocation. Both responses were dose-dependently suppressed by the administration of dexamethasone or cyclosporin A in vivo. We concluded that airway eosinophilic inflammation can be controlled by agents capable of downregulating IL-5 production in T cells.

Objective: The aim of this study was to compare Sephadex G-200 (Sephadex)-induced airway hyperresponsiveness (AHR) and pulmonary eosinophilia among some rat strains.¶Materials: Sprague-Dawley (SD), Brown-Norway (BN), Fischer 344 (Fischer), Lewis and Wistar-Kyoto (WKY) rats were used.¶Methods: Sephadex (0.5 mg/animal) was intravenously administered on days 0, 2 and 5. Measurement of AHR using serotonin and bronchoalveolar lavage (BAL) was performed on day 7.¶Results: The Lewis strain exhibited significant AHR to Sephadex but the BN, Fischer and WKY strains did not. Additionally, the degree of AHR in Lewis rats was smaller than in SD rats throughout the study. Eosinophils in BAL fluid, however, increased in each strain, and the magnitude of the response was BN > Lewis > WKY > Fischer. Both the AHR and pulmonary eosinophilia in Lewis rats were inhibited by dexamethasone (0.1 mg/kg, p.o. × 3).¶Conclusion: These results indicate that the Lewis rat is a useful strain for analysis of the mechanism of Sephadex-induced AHR and airway inflammation.