Search

Purpose: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). Study design: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. Methods: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. Results: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. Conclusion: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is an acute, self-limiting, febrile systemic vasculitis of unknown cause associated with the development of coronary artery lesions (CALs) during childhood. Damage-associated molecular patterns (DAMPs) from cell death and oxidative stress have been shown to be involved in the development of KD vasculitis. Interleukin (IL)-33 is released from damaged endothelial cells and acts as a DAMP. We studied whether IL-33 and its receptor (ST2) might be involved in KD pathogenesis. Serum levels of soluble ST2 (sST2) in KD patients were measured before their first therapy. Furthermore, we investigated the impact of IL-33 on human coronary artery endothelial cells (HCAECs). Serum levels of sST2 were significantly higher in KD patients with CALs than in those with normal coronary arteries. In vitro, IL-33 upregulated the expression of ST2L and increased production of sST2, IL-6, IL-8, and monocyte chemoattractant protein−1 in HCAECs in a time- and concentration-dependent manner. Moreover, IL-33 induced significantly greater production of IL-6 and IL-8 in HCAECs compared to the condition stimulated with isoconcentration of tumor necrosis factor-α. The results of the present study suggest that the IL-33/ST2 axis might be involved in the development of KD vasculitis. The IL-33/ST2 axis may be a therapeutic target for the treatment of KD. [ABSTRACT FROM AUTHOR]

Cryopyrin-associated periodic syndrome (CAPS) is one of the autoinflammatory disorders caused by mutations in NLRP3 gene. The over-production of interleukin (IL)-1β induced by NLRP3 gene mutations plays an important role in the pathophysiology of CAPS. We diagnosed 3 patients with CAPS, who were lineal family members having a novel mutation of NLRP3 gene. The objective of this report is to compare the characteristics of symptoms and differences in the therapeutic responses of them, who had the same mutation. In addition, we aimed to examine the usefulness of cytokine measurement for diagnosis or determination of treatment effect of CAPS. A 5-year-old Japanese boy (proband) came to our hospital because of short stature, reached the diagnosis of Muckle-Wells syndrome (MWS) due to a mutation in NLRP3 gene, which had not been reported so far (p.G328E, c.G983A). His mother and grandmother harbored the same mutation of NLRP3. We measured serum concentrations of cytokines in the proband assessed by flow-cytometric bead array. All of them had episodic skin eruptions with conjunctivitis, hearing loss, and arthralgia, but not periodic fever, cold-triggered episodes, and chronic aseptic meningitis. Only the proband had short stature. Canakinumab therapy led to a prompt relief of symptoms and normalized laboratory data in all patients. Audiograms demonstrated an improved hearing level in the proband, but not two others despite of the same mutation. All cytokines did not show any characteristic findings. Sensorineural hearing loss and itchless rash but not serum cytokine profile deserved attention to the diagnosis and treatment start of CAPS. The early intervention of IL-1β blockade may reduce the chance of complete deafness in patients with CAPS. [ABSTRACT FROM AUTHOR]

A 38-year-old male with no past history of illnesses visited the out-patient clinic of Nerima Hikarigaoka Hospital complaining of dizziness and persistent anal bleeding. There was a significant anemia on a blood test and colonoscopy showed a thrombus in a markedly swollen internal hemorrhoid. Contrast-enhanced computed tomography (CT) showed a poorly demarcated area with early face enhancement on the right side of the rectum and anal canal. Based on these findings, an arterio-venous malformation (AVM) of the rectum was suspected. Abdominal angiography showed abnormal vessels receiving a blood supply from the bilateral superior rectal arteries. We suspected that the AVM in the rectum was the cause of the hemorrhage from the internal hemorrhoid, and therefore performed embolization of the AVM. Thereafter, the hemorrhage from the internal hemorrhoid stopped completely and the anemia improved to the normal level, without the need for treatment for the internal hemorrhoid. Colonoscopy performed 6 months after embolization showed shrinkage of the internal hemorrhoid. To the best of our knowledge, there are no reports stating a relationship between rectal AVM and internal hemorrhoids. However, we consider that contrast-enhanced CT can be used to detect vessel abnormalities related to severe bleeding of the internal hermorrhoids in patients with internal hemorrhoids and severe anemia. [ABSTRACT FROM AUTHOR]

The article describes the case of a 12-year-old boy with hypertrophic cardiomyopathy (HCM) who was found with a novel de novo mutation of ß-cardiac myosin heavy chain gene. The patient's condition was incidentally detected on electrocardiography. To identify mutations in genes for sarcomeric proteins, DNA samples were extracted from the peripheral blood of the patient. He was treated with propanol for seven months but remained asymptomatic and clinical findings remained almost unchanged.

Purpose: To evaluate the high-resolution computed tomography (HRCT) findings of novel influenza virus (n-IFV) pneumonia and compare them with the findings for seasonal (s-IFV) pneumonia. Materials and methods: We evaluated 29 cases of pure IFV pneumonia that occurred between 1990 and 2010. We evaluated the existence, extent, and patterns of HRCT findings and compared these features between s-IFV and n-IFV. Results: Consolidation was less frequent in s-IFV than in n-IFV (40.0 vs. 84.2%, respectively; p = 0.014). Consolidation with a loss of volume was frequent in n-IFV (62.5%). There was no significant difference in the occurrence of ground-glass opacity (GGO) between s-IFV and n-IFV (100 vs. 84.2%, respectively). GGO with reticular opacities was more frequent in s-IFV than in n-IFV (70.0 vs. 25.0%, respectively; p = 0.024). The frequency of nodules was not significantly different between the two groups. The mosaic pattern was more frequent in s-IFV than in n-IFV patients (80.0 vs. 15.8%, respectively; p = 0.0007). Mucoid impaction was more frequent in patients with n-IFV than with s-IFV (52.6 vs. 10.0%, respectively; p = 0.025). Conclusions: Consolidation and mucoid impaction were more frequent in n-IFV, whereas GGO with reticular opacities and a mosaic pattern occurred more frequently in s-IFV; otherwise, there were no significant differences between the two groups. [ABSTRACT FROM AUTHOR]

Objective: The elemental diet is one of the effective therapies for inflammatory bowel disease. However, the mechanism remains unclear, and there have never been reports about the inhibitory effects of amino acids in human monocytes/macrophages. We investigated the inhibitory effects of amino acids on cytokine production or expression of adhesion molecules that are involved in inflammatory diseases, in human monocytes/macrophages. Methods: We examined the inhibitory effects of cysteine, histidine or glycine on the induction of nuclear factor-κB (NF-κB) activation, expression of intracellular adhesion molecule-1 (ICAM-1, CD54) and production of interleukin-8 (IL-8) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs) stimulated with tumor necrosis factor-α (TNF-α). Results: Cysteine, histidine and glycine significantly reduced the activation of NF-κB in THP-1 cells stimulated with TNF-α. In addition, cysteine and histidine significantly inhibited the expression of ICAM-1 and production of IL-8 in THP-1 cells and PBMCs. Conclusions: Our results suggest that cysteine and histidine exhibit anti-inflammatory effects in THP-1 cells, and may be responsible for the efficacy of treatment in inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

Objective: Human thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine, promotes inflammatory T helper type 2 cell (Th2) differentiation of naive CD4 T cells. TSLP is highly produced in keratinocytes of patients with atopic dermatitis and bronchial epithelia of patients with asthma and was thought to be a master switch for allergic inflammation. We sought to examine the effect of TSLP in human monocytes/macrophages. Methods: The effect of TSLP on the expression of cell surface antigens (CD11c, CD16, CD54, CD80, CD86, and HLA-DR) in peripheral blood CD14 monocytes/macrophages was examined. Results: TSLP enhanced the expression of CD80 in peripheral blood CD14 monocytes/macrophages but not that of other cell surface antigens. It was associated with an increased percentage of CD14, CD80, CD11c, and HLA-DR cells, which was consistent with the increased differentiation of myeloid dendritic cells. Conclusions: TSLP induces CD80 expression in human peripheral blood CD14 monocytes/macrophages; this indicates monocyte/macrophage activation. This may be associated with their differentiation into myeloid dendritic cells. [ABSTRACT FROM AUTHOR]

A 68-year-old man, admitted for the treatment of recurrent cholangitis after a pancreatoduodenectomy (PD) performed 3 years previously was diagnosed as having multiple hepaticolithiasis. On laparotomy, the hepatic artery was not recognized. The anastomosed common hepatic duct was obstructed, and a fistula had been formed between the right hepatic duct and the Roux limb of the jejunum. Lithotripsy was performed from this fistula and it was reanastomosed. Angiography was performed postoperatively and it revealed common hepatic artery injury, most likely to have occurred during the previous PD. The patient's postoperative course was uneventful and he has been asymptomatic for 8 months after the operation, indicating that reanastomosis of the fistula can be an effective method. The stricture of the anastomosis was suspected to be mainly due to cholangial ischemia, because no episode of anastomotic leak or retrograde biliary infection had occurred during the PD perioperative period. There are several reports of late stricture of anastomosis 5 or more years after cholangiojejunostomy. This patient, therefore, requires further long-term follow up. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that theophylline modulates NF-κB activation in mast cells and pulmonary epithelial cells. We examined whether or not this modulation of NF-κB activation by theophylline is due to inhibition of the degradation of the IκBα protein, which suppresses NF-κB activation. TNF-α-induced NF-κB activation in a human pulmonary epithelial cell line (A549) was evaluated by Western blotting and a chloramphenicol acetyltransferase (CAT) assay. Expression of the IκBα protein was evaluated by Western blotting. Western blotting of nuclear extracts of A549 cells demonstrated that theophylline suppresses NF-κB-p65 nuclear translocation. The CAT assay indicated that NF-κB-dependent reporter gene expression is inhibited in A549 cells pretreated with theophylline. Western blotting of cytoplasmic extracts of A549 cells revealed that this inhibition was linked to theophylline-induced protection of expression of the IκBα protein. Moreover, theophylline inhibited interleukin-6 production induced by TNF-α in A549 cells. These findings are consistent with the idea that theophylline suppresses the production of proinflammatory cytokines via inhibition of NF-κB activation through protection of the IκBα protein. [ABSTRACT FROM AUTHOR]

Reports on a case of Caffey disease in a six-month-old girl with striking magnetic resonance imaging findings. Symptoms of painful soft tissue swelling and cortical thickening of the underlying bones in this rare and poorly understood disease; Many hypotheses for its pathogenesis, with symptomatic treatment and recovery by patient without any deformity; Characteristic findings of plain radiography in Caffey disease preceded by abnormal MRI findings.

Human rhinovirus species C (HRV-C) was recently discovered, and this virus has been associated with various acute respiratory illnesses (ARI). However, the molecular evolution of the major antigens of this virus, including VP1, VP2, and VP3, is unknown. Thus, we performed complete VP1, VP2, and VP3 gene analyses of 139 clinical HRV-C strains using RT-PCR with newly designed primer sets and next-generation sequencing. We assessed the time-scale evolution and evolutionary rate of these genes using the Bayesian Markov chain Monte Carlo method. In addition, we calculated the pairwise distance and confirmed the positive/negative selection sites in these genes. The phylogenetic trees showed that the HRV-C strains analyzed using these genes could be dated back approximately 400 to 900 years, and these strains exhibited high evolutionary rates (1.35 to 3.74 × 10−3 substitutions/site/year). Many genotypes (>40) were confirmed in the phylogenetic trees. Furthermore, no positively selected site was found in the VP1, VP2, and VP3 protein. Molecular modeling analysis combined with variation analysis suggested that the exterior surfaces of the VP1, VP2 and VP3 proteins are rich in loops and are highly variable. These results suggested that HRV-C may have an old history and unique antigenicity as an agent of various ARI. [ABSTRACT FROM AUTHOR]