Clitoral keloids after female genital mutilation/cutting

PubMed Central

Birge, Özer; Akbaş, Murat; Özbey, Ertuğrul Gazi; Adıyeke, Mehmet

2016-01-01

We aimed to describe the presentation of long-term complications of female genital mutilation/cutting and the surgical management of clitoral keloids secondary to female genital mutilation/cutting. Twenty-seven women who underwent surgery because of clitoral keloid between May 2014 and September 2015 in Sudan Nyala Turkish Hospital were evaluated in this retrospective descriptive case series study. The prevalence of type 1, type 2, and type 3 female genital mutilation/cutting were 3.7%, 22.2%, and 74.1%, respectively (type 1: 1/27, type 2: 6/27, and type 3: 20/27). All patients had long-term health problems (dysuria, chronic pelvic pain, vaginal discharge, and chronic pruritus) and sexual dysfunction. Keloids were removed by surgical excision. There were no postoperative complications in any patient. Although clitoral keloid lesions can be seen after any type of female genital mutilation/cutting, they usually develop after type 3 female genital mutilation/cutting. Most of these keloids were noticed after menarche. Keloids can be removed by surgical excision and this procedure can alleviate some long-term morbidities of female genital mutilation/cutting. PMID:28913112

Plantar keloids: diagnostic and therapeutic issues in six patients.

PubMed

Vanhaecke, C; Hickman, G; Cavelier-Balloy, B; Masson, V; Duron, J-B; Gorj, M; May, P; Schneider, P; Vilmer, C; Bagot, M; Battistella, M; Petit, A

2015-07-01

Keloids are benign fibro-proliferative skin lesions that very rarely occur on the soles. Because of their rarity, the diagnosis of plantar keloids can be difficult. We describe the clinical and histopathological characteristics of eight plantar keloids. All patients presenting with plantar keloids between 2005 and 2012 in our Dermatology unit were retrospectively included. Diagnosis was definitely established by re-reading of pathological slides in all cases. Clinical characteristics, histopathological features, treatments given and their results were collected. Six patients were included. Five patients had a single plantar keloid and one had three lesions. They all were of African descent. Only one patient remembered of a previous injury at the site of the keloid. Three patients presented with associated extra-plantar keloids. In four patients, the diagnosis of keloid was not initially suspected clinically or histologically. Re-reading of the clinical photographs showed that the eight plantar keloids shared common morphological features, leading to a distinctive clinical picture, defined by a hardened lesion of rounded or polycyclic shape, with a pink surface crossed by keratotic furrows and the presence of a hyperkeratotic rim. Concerning pathological features, typical hyalinized collagen can be missing and deep fibrosis should not rule out the diagnosis of keloid. Intralesional injection of triamcinolone acetonide and orthopaedic shoes were useful. All patients who had surgical excision presented recurrence. The knowledge of the clinical features of plantar keloids is helpful to the diagnosis. There is no well-established treatment, but supportive measures are important. © 2014 European Academy of Dermatology and Venereology.

[Establishment of immortal lymphoblastoid cell bank of keloids pedigree].

PubMed

Song, Mei; Gao, Jian-hua; Yan, Xin; Liu, Xiao-jun; Chen, Yang

2006-11-01

To provide perpetual research materials for long term studies by establishing immortal lymphoblastoid cell bank of keloids pedigree. The immortal lymphoblastoid cell lines of keloids pedigree were established by Epstein-Barr virus transformation of peripheral blood B lymphocytes. 27 immortal lymphoblastoid cell lines of keloids pedigree were obtained successfully, all of the immortal lymphoblastoid cell lines were successfully revivificated after been frozen in liquid nitrogen. It is important to establish immortal lymphoblastoid cell bank of keloids pedigree and provide long-term DNA materials for deep study of keloids in the future.

Causal network analysis of head and neck keloid tissue identifies potential master regulators.

PubMed

Garcia-Rodriguez, Laura; Jones, Lamont; Chen, Kang Mei; Datta, Indrani; Divine, George; Worsham, Maria J

2016-10-01

To generate novel insights and hypotheses in keloid development from potential master regulators. Prospective cohort. Six fresh keloid and six normal skin samples from 12 anonymous donors were used in a prospective cohort study. Genome-wide profiling was done previously on the cohort using the Infinium HumanMethylation450 BeadChip (Illumina, San Diego, CA). The 190 statistically significant CpG islands between keloid and normal tissue mapped to 152 genes (P < .05). The top 10 statistically significant genes (VAMP5, ACTR3C, GALNT3, KCNAB2, LRRC61, SCML4, SYNGR1, TNS1, PLEKHG5, PPP1R13-α, false discovery rate <.015) were uploaded into the Ingenuity Pathway Analysis software's Causal Network Analysis (QIAGEN, Redwood City, CA). To reflect expected gene expression direction in the context of methylation changes, the inverse of the methylation ratio from keloid versus normal tissue was used for the analysis. Causal Network Analysis identified disease-specific master regulator molecules based on downstream differentially expressed keloid-specific genes and expected directionality of expression (hypermethylated vs. hypomethylated). Causal Network Analysis software identified four hierarchical networks that included four master regulators (pyroxamide, tributyrin, PRKG2, and PENK) and 19 intermediate regulators. Causal Network Analysis of differentiated methylated gene data of keloid versus normal skin demonstrated four causal networks with four master regulators. These hierarchical networks suggest potential driver roles for their downstream keloid gene targets in the pathogenesis of the keloid phenotype, likely triggered due to perturbation/injury to normal tissue. NA Laryngoscope, 126:E319-E324, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Electrochemotherapy treatment of a recalcitrant earlobe keloid scar with chronic lymphocytic leukaemia infiltration.

PubMed

Sainsbury, D C G; Allison, K P; Muir, T

2010-10-01

Electrochemotherapy, a tumour ablation modality, which facilitates intracellular delivery of poorly-permeable cytotoxic drugs, such as bleomycin, has shown promising results in the treatment of cutaneous and subcutaneous melanomatous and non-melanomatous metastases. We report the case of a 52-year-old Caucasian gentleman with a keloid scar to his left earlobe that developed following a piercing. Despite multiple intralesional steroidal injections, five intralesional excisions and a course of superficial radiotherapy the keloid scar remained over nine years later. For 15 years the patient had also suffered chronic lymphocytic leukaemia with no nodal disease or systemic involvement. However, histological analysis of the final surgical excision specimen showed chronic lymphocytic leukaemia infiltration of the keloid scar. Further surgical excision seemed unwise considering the recalcitrance of the keloid scar. Additionally, no systemic chemotherapy treatment options were feasible. Electrochemotherapy was performed under local anaesthesia with the aim of eradicating the chronic lymphocytic leukaemia deposit within the keloid lesion. Four sessions of electrochemotherapy using bleomycin were deployed over 11 months. A deep core biopsy of the treated keloid performed three months following the last electrochemotherapy session showed no evidence of chronic lymphocytic leukaemia. Serendipitously, following the initial electrochemotherapy treatment no further growth of the keloid scar was observed. Furthermore, subsequent electrochemotherapy led to a substantial reduction in size of the keloid sustained for 14 months at last follow-up. This report highlights the exciting potential of electrochemotherapy and bleomycin in the treatment of recalcitrant scars. Larger, well-designed clinical and in-vitro studies are required to further elucidate the exact role, mechanism and cost-effectiveness of electrochemotherapy in this area. Copyright 2010 British Association of Plastic

Lipid nano-bubble combined with ultrasound for anti-keloids therapy.

PubMed

Wang, Xiao Qing; Li, Zhou-Na; Wang, Qi-Ming; Jin, Hong-Yan; Gao, Zhonggao; Jin, Zhe-Hu

2018-03-01

Keloids were characterized by excessive growth of fibrous tissues, and shared several pathological characteristics with cancer. They did put physical and emotional stress on patients in that keloids could badly change appearance of patients. N-(4-hydroxyphenyl) retinamide (4HPR) showed cytotoxic activity on a wide variety of invasive-growth cells. Our work was aim to prepare N-(4-hydroxyphenyl) retinamide-loaded lipid microbubbles (4HPR-LM) combined with ultrasound for anti-keloid therapy. 4HPR-loaded liposomes (4HPR-L) were first prepared by film evaporation method, and then 4HPR-LM were manufactured by mixing 4HPR-L and perfluoropentane (PFP) with ultrasonic cavitation method. The mean particle size and entrapment efficiency 4HPR-LM were 113 nm and 95%, respectively. The anti-keloids activity of 4HPR-LM was assessed with BALB/c nude mice bearing subcutaneous xenograft keloids model. 4HPR-LM, combined with ultrasound, could significantly induce apoptosis of keloid fibroblasts in vitro and inhibited growth of keloids in vivo. Thus, 4HPR-LM could be considered as a promising agent for anti-keloids therapy.

Heat Shock Protein 90 Inhibitor Decreases Collagen Synthesis of Keloid Fibroblasts and Attenuates the Extracellular Matrix on the Keloid Spheroid Model.

PubMed

Lee, Won Jai; Lee, Ju Hee; Ahn, Hyo Min; Song, Seung Yong; Kim, Yong Oock; Lew, Dae Hyun; Yun, Chae-Ok

2015-09-01

The 90-kDa heat-shock protein (heat-shock protein 90) is an abundant cytosolic chaperone, and inhibition of heat-shock protein 90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) compromises transforming growth factor (TGF)-β-mediated transcriptional responses by enhancing TGF-β receptor I and II degradation, thus preventing Smad2/3 activation. In this study, the authors evaluated whether heat-shock protein 90 regulates TGF-β signaling in the pathogenesis and treatment of keloids. Keloid fibroblasts were treated with 17-AAG (10 μM), and mRNA levels of collagen types I and III were determined by real-time reverse- transcriptase polymerase chain reaction. Also, secreted TGF-β1 was assessed by enzyme-linked immunosorbent assay. The effect of 17-AAG on protein levels of Smad2/3 complex was determined by Western blot analysis. In addition, in 17-AAG-treated keloid spheroids, the collagen deposition and expression of major extracellular matrix proteins were investigated by means of Masson trichrome staining and immunohistochemistry. The authors found that heat-shock protein 90 is overexpressed in human keloid tissue compared with adjacent normal tissue, and 17-AAG decreased mRNA levels of type I collagen, secreted TGF-ß1, and Smad2/3 complex protein expression in keloid fibroblasts. Masson trichrome staining revealed that collagen deposition was decreased in 17-AAG-treated keloid spheroids, and immunohistochemical analysis showed that expression of collagen types I and III, elastin, and fibronectin was markedly decreased in 17-AAG-treated keloid spheroids. These results suggest that the antifibrotic action of heat-shock protein 90 inhibitors such as 17-AAG may have therapeutic effects on keloids.

Effect of triamcinolone in keloids morphological changes and cell apoptosis.

PubMed

dos Santos, João Márcio Prazeres; de Souza, Cláudio; de Vasconcelos, Anílton César; Nunes, Tarcizo Afonso

2015-06-01

to assess the effects of injectable triamcinolone on keloid scars length, height and thickness, and on the number of cells undergoing apoptosis. This study consists in a prospective, controlled, randomized, single-blinded clinical trial, conducted with fifteen patients with ear keloids divided into two groups: group 1 - seven patients undergoing keloid excisions, and group 2 - eight patients undergoing keloid excisions after three sessions of infiltration with one ml of Triamcinolone hexacetonide (20mg/ml) with three week intervals between them and between the last session and surgery. The two groups were homogeneous regarding age, gender and evolution of the keloid scar. The keloid scars of patients in group 2 were measured for the length, height and thickness before triamcinolone injection and before surgery. A blinded observer performed morphological detailing and quantification of cells in hematoxylin-eosin-stained surgical specimens. An apoptotic index was created. The apoptotic index in group 1 was 56.82, and in group 2, 68.55, showing no significant difference as for apoptosis (p=0.0971). The reduction in keloid dimensions in Group 2 was 10.12% in length (p=0.6598), 11.94% in height (p=0.4981) and 15.62% in thickness (p=0.4027). This study concluded that the infiltration of triamcinolone in keloid scars did not increase the number of apoptosit and did not reduce keloids' size, length, height or thickness.

Ursodeoxycholic Acid Ameliorates Intrahepatic Cholestasis Independent of Biliary Bicarbonate Secretion in Vil2kd/kd Mice.

PubMed

Hatano, Ryo; Kawaguchi, Kotoku; Togashi, Fumitaka; Sugata, Masato; Masuda, Shizuka; Asano, Shinji

2017-01-01

Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid that possesses many pharmacological effects, including increasing bile flow, changing the hydrophobicity of the bile acid pool, and modulation of the immune response. UDCA has been approved for treating cholestatic liver disease, such as primary biliary cholangitis. However, several unanticipated severe side effects of UDCA are observed in cholestatic patients, and its pharmacological benefits remain controversial. We reported that ezrin-knockdown (Vil2 kd/kd ) mice exhibited severe hepatic injury because of a functional disorder in bile duct fluidity and alkalinity regulation, resembling human intrahepatic cholestatic disease. Here we used Vil2 kd/kd mice as a cholestatic model to investigate the pharmacological effects of UDCA. We investigated the effects of oral and parenteral administration of UDCA on Vil2 kd/kd mice. In Vil2 kd/kd mice, fed a 0.5% (w/w) UDCA diet for 3 weeks, hepatic injury was exacerbated, although oral administration of a lower dose of UDCA slightly improved hepatic function in Vil2 kd/kd mice. On the other hand, intraperitoneal administration of UDCA (50 mg/kg/d) ameliorated hepatic function and markedly reduced periductal fibrosis and cholangiocyte proliferation in Vil2 kd/kd mice although biliary pH and HCO 3 - concentration were not improved. The expression levels of inflammatory and profibrotic genes were also significantly decreased in these mice. Furthermore, UDCA prevented cholangiocytes from hydrophobic bile acid-induced cytotoxicity independent of extracellular pH in in vitro experiments. These results suggest that an appropriate dosage of UDCA can ameliorate the intrahepatic cholestasis in Vil2 kd/kd mice without changing the biliary bicarbonate secretion.

Effect of mitomycin C on keloid fibroblasts: an in vitro study.

PubMed

Simman, Richard; Alani, Hashim; Williams, Frances

2003-01-01

Keloids are the result of aberrant wound healing of human skin after dermal injury. Therapeutic options include excision followed by radiation therapy, steroid injection, and compression with silicone sheets among others. Local invasion and recurrence after excision has provoked interest in treating keloids as neoplasms. The purpose of this study was to determine the effect of mitomycin C (MMC) on keloid fibroblasts. Keloid fibroblasts obtained from five different patients were exposed to MMC. A control group of normal and keloid cells was treated with phosphate buffered saline only. Contrast microscopy showed a decrease of fibroblast density during the 3 weeks after exposure for normal and keloid fibroblasts relative to untreated fibroblasts. This was confirmed by total cell counts ( = 0.1) and measurement of DNA synthesis. By the third week, there was a recovery in DNA synthesis and increased cell count for some of the treated fibroblasts. We concluded that at an appropriate concentration, MMC shows proliferation of keloid fibroblasts in vitro for a period of 3 weeks. This agent may be considered in clinical trials after surgical excision of keloids.

Epithelial-mesenchymal transition in keloid tissues and TGF-β1-induced hair follicle outer root sheath keratinocytes.

PubMed

Yan, Li; Cao, Rui; Wang, Lianzhao; Liu, Yuanbo; Pan, Bo; Yin, Yanhua; Lv, Xiaoyan; Zhuang, Qiang; Sun, Xuejian; Xiao, Ran

2015-01-01

Keloid is a skin fibrotic disease with the characteristics of recurrence and invasion, its pathogenesis still remains unrevealed. The epithelial-mesenchymal transition (EMT) is critical for wound healing, fibrosis, recurrence, and invasion of cancer. We sought to investigate the EMT in keloid and the mechanism through which the EMT regulates keloid formation. In keloid tissues, the expressions of EMT-associated markers and transforming growth factor (TGF)-β1/Smad3 signaling were examined by immunohistochemistry. In the keloid epidermis and dermal tissue, the expressions of genes related to the regulation of skin homeostasis, fibroblast growth factor receptor 2 (FGFR2) and p63, were analyzed using quantitative real-time polymerase chain reaction. The results showed that accompanying the loss of the epithelial marker E-cadherin and the gain of the mesenchymal markers fibroblast-specific protein 1 (FSP1) and vimentin in epithelial cells from epidermis and skin appendages, and in endothelial cells from dermal microvessels, enhanced TGF-β1 expression and Smad3 phosphorylation were noted in keloid tissues. Moreover, alternative splicing of the FGFR2 gene switched the predominantly expressed isoform from FGFR2-IIIb to -IIIc, concomitant with the decreased expression of ΔNp63 and TAp63, which changes might partially account for abnormal epidermis and appendages in keloids. In addition, we found that TGF-β1-induced hair follicle outer root sheath keratinocytes (ORSKs) and normal skin epithelial cells underwent EMT in vitro with ORSKs exhibiting more obvious EMT changes and more similar expression profiles for EMT-associated and skin homeostasis-related genes as in keloid tissues, suggesting that ORSKs might play crucial roles in the EMT in keloids. Our study provided insights into the molecular mechanisms mediating the EMT pathogenesis of keloids. © 2015 by the Wound Healing Society.

Upregulation of proinflammatory genes in skin lesions may be the cause of keloid formation (Review)

PubMed Central

DONG, XIANGLIN; MAO, SHAOLIN; WEN, HAO

2013-01-01

It was previously demonstrated that the main cause behind keloid formation may be keloid fibroblast abnormalities, which are closely associated with the microenvironment of the keloid lesion. The post-traumatic and chronic inflammation of the keloid lesion area suggest that inflammatory mediators play an important role in the keloid microenvironment and are crucial for keloid fibroblast abnormalities. In this study, we hypothesized that the mechanism underlying keloid formation may involve the continuous upregulation of proinflammatory gene expression in keloid lesions. This hypothesis may explain the inflammatory response, invasive growth and recurrence following resection of keloids, as well as the selective localization of keloids in specific parts of a patient’s body and the differences in localization among different patients. PMID:24649037

Treatment of earlobe keloids using the cobalt 60 teletherapy unit.

PubMed

Malaker, Kamal; Zaidi, Mustafa; Franka, Mohamad Rida

2004-06-01

The purpose of this study was to develop an easily accessible technique for the delivery of postoperative radiotherapy for the treatment of earlobe keloids. Forty-seven earlobe keloids were given postoperative radiation using the smallest achievable half field Telecobalt technique. Results showed 41 (87.2%) of treated patients' postoperative scars remained free from recurrent keloid formation. Acute reactions were minimal and patient compliance was excellent. In conclusion, the technique described in this study for the delivery of postoperative radiation to earlobe keloids should be readily available in areas of high prevalence. Results are comparable to previously used radiotherapy techniques.

A case of congenital corneal keloid.

PubMed

Song, Jong-Suk; Kwon, Sangwon; Shyn, Kyung-Hwan

2005-06-01

To describe a case of unilateral comeal keloid and present the clinical and histopathological findings and the management. A 23-year-old Asian male patient was examined for a white spot on the left cornea that had been present since birth. On biomicroscopic examination, a well-demarcated vascularized comeal mass was found located nasal to the center. The pupil was displaced superiorly, and gonioscopic examination showed peripheral iridocomeal adhesion at 12 o'clock. The patient underwent penetrating keratoplasty. Histopathologic study showed a variously thickened epithelial layer, an absence of Bowman's layer, subepithelial fibrovascular hyperplasia, and an absence of dermal elements. These histopathologic findings suggested a congenital comeal keloid. The central graft comea remained clear at 18 months after surgery and the patient was satisfied with the result. Penetrating keratoplasty may be an effective surgical option for congenital keloids in young adult patients.

Keloid scar (image)

MedlinePlus

... tissue at the site of a healed skin injury. They often create a thick, puckered effect simulating a tumor. Keloids may be reduced in size by freezing (cryotherapy), external pressure, corticosteroid injections, laser treatments, radiation, or surgical removal.

Is There an Association between Keloids and Blood Groups?

PubMed

Mouhari-Toure, Abas; Saka, Bayaki; Kombaté, Koussaké; Akakpo, Sefako; Egbohou, Palakiyem; Tchangaï-Walla, Kissem; Pitche, Palokinam

2012-01-01

Objective. The aim of the study is to investigate the possible associations between the blood groups ABO and Rhesus systems and the presence of keloids in patients with black skin. Method. This case-control study was conducted between September 2007 and August 2011 comparing dermatologic outpatients with keloids to matched controls recruited in preanesthetic consultation at Tokoin Teaching Hospital of Lomé (Togo). Results. The distribution of different ABO blood groups and Rhesus blood groups in both groups (cases versus controls) was not significantly different. This distribution of different blood groups was superimposed on the general population of blood donors at the National Blood Transfusion Center of Lomé. Univariate analysis between each blood group and the presence of keloid does not yield any statistically significant association between blood groups and presence of keloids in the subjects. Conclusion. The study shows no significant association between blood groups and the presence of keloids in our patients. Further investigation needs to be conducted to elucidate this hypothesis further by conducting multicenter studies of several ethnic groups.

Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.

Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloidmore » fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated.« less

Oxygen consumption of keloids and hypertrophic scars.

PubMed

Ichioka, Shigeru; Ando, Taichi; Shibata, Masahiro; Sekiya, Naomi; Nakatsuka, Takashi

2008-02-01

The oxygen consumption of keloids and hypertrophic scars has never been quantitatively presented, although abnormal metabolic conditions must be associated with their pathophysiology. We invented an original measurement system equipped with a Clark oxygen electrode for ex vivo samples. The measurement of a mouse wound-healing model revealed immature repairing tissues consumed more oxygen than mature tissues. This finding is in accord with the current thinking and supported the validity of our measurement system. The analysis of fresh human samples clearly demonstrated the high oxygen consumption rate of keloid hypertrophic scars and the comparatively low consumption of mature scars. A high oxygen consuming potential, as well as insufficient oxygen diffusion, may possibly contribute to the pathophysiology of keloids and hypertrophic scars.

Application of mitomycin-C for head and neck keloids.

PubMed

Stewart, Charles E; Kim, John Y

2006-12-01

Keloids of the head and neck are a relatively common entity in darker-skinned races, occurring in 5%-15% of skin wounds. Keloids are fibrotic lesions that are a result of an abnormal wound-healing process that lacks control of the mechanisms that regulate tissue repair and regeneration. The proliferation of normal tissue-healing processes results in scarring that enlarges well beyond the original wound margins. Many treatment modalities for keloids have been tried with variable amounts of success. Surgical excision, compressive therapy, silicon dressings, corticosteroid injections, radiation, cryotherapy, interferon therapy, and laser therapy have all been used alone or in combination. Despite this wide range of available treatments, recurrence rates typically remain in the 50%-70% range. In this study, we present our results in a series of 10 patients who were treated with surgical excision of head and neck keloids and the application of topical mitomycin-C. Mitomycin-C is a chemotherapeutic agent that inhibits DNA synthesis and fibroblast proliferation. It has been used in ophthalmologic procedures and airway surgery to decrease scar formation. In these 10 patients, we combined surgical excision of keloids with the application of topical mitomycin-C. The patients were then followed postoperatively for recurrence (range, 7-14 months). We have found topical application of mitomycin-C to be an effective therapy for prevention of keloid recurrence in the head and neck, with a success rate of 90% as reported in this series.

[Keloid scars of the external ear: a non solved problem].

PubMed

Bejarano Serrano, M; Parri Ferrandis, F J; García Smith, N I; Martínez-Herrada, S; Manzanares Quintela, A; Albert Cazalla, A

2014-01-01

The external ear is a location with high risk of keloid scar formation. Its incidence is growing since general use of piercings and performance of plastic surgery of the external ear. The external ear keloid can be a devasting process for adolescent population which is worried about their appearance. Our aim is to attract attention about the risk of keloid scars of the external ear, reviewing our experience. After dismissing radiotherapy, corticoid infiltration and surgical removal are the most used options, with a high recurrence risk. We have reviewed traumatic, surgical and piercing wounds of the external ear, with a subsequent keloid formation treated in our outpatient clinic, collecting data about wound etiology, treatment and results. During the last 10 years we have found 11 keloid scars, 2 of them improved with topical corticosteroid. Treatment has been surgical in 9 cases, 4 of them with skin graft: 5 recovered and 4 recurred; 2 of them were reoperated. 2 of them were treated with intralesional corticosteroid solely, one recovered and the other one had improved. Treatment management of keloid scars is complex and there isn't a procedure with superior results than the others. Risk of complication must be explained within adolescent population.

The pivotal role of inflammation in scar/keloid formation after acne

PubMed Central

Shi, Chao; Zhu, Jianyu; Yang, Degang

2017-01-01

ABSTRACT Most keloids are clinically observed as solid nodules or claw-like extensions. However, they appear hypoechoic on ultrasound images and are therefore easily confused with liquid features such as blood or vessels. The pathological manifestations of typical keloids also include prominent, thick blood vessels. The existing classification of scars fails to reflect the natural history of keloids. The outer characteristics of a typical keloid include bright red hyperplasia with abundant vessels, suggesting the importance of vascular components in the process of scar formation and prompting consideration of the role of inflammation in the development of granular hyperplasia. Additionally, we further considered the potential effectiveness of oral isotretinoin for severe keloids secondary to severe acne. We also explored different principles and applications related to 5-fluorouracil (5-FU), pulsed dye laser (PDL), and CO2 laser treatments for scars. PMID:29707102

Piercing Ear Keloid: Excision Using Loupe Magnification and Topical Liquid Silicone Gel as Adjuvant

PubMed Central

Ramesh, Bellam A.; Mohan, J.

2018-01-01

Background: Keloid is an abnormal growth of scar at the site of skin injury, which usually does not regress. It proliferates beyond the original scar. The ear keloid usually develops after piercing injury to wear ornaments. A patient usually asks for removal of keloid, as it is aesthetically unpleasant. Patient may sometimes complain of itching and pain. Aim: The study was conducted to analyze results following excision of keloid with its tract and topical silicone gel as the postsurgical adjuvant. Materials and Methods: Ear keloids measuring less than 0.5cm or more than 5cm in maximum dimension were excluded from the study. Nonpiercing causes such as burns, trauma, and recurrent keloid were excluded from the study. The study was carried out on 22 patients who had keloid because of piercing injury, including 4 cases with both ear keloids. Of 26 ear keloids, 19 had the tract or connecting tissue. The lesion was excised under anesthesia using magnification. For all the operated cases, topical liquid silicone gel was used as postsurgical adjuvant therapy. The method of application of topical silicone gel was taught to each patient and was considered significant. Result: The magnification helped in identification of tract in 73% of the cases in this study. Twenty patients had successfully responded to proposed treatment, and two patients developed recurrence while using topical silicone gel as the adjuvant. These two patients were managed with conventional triamcinolone injection. Conclusion: The topical silicone gel as postsurgical adjuvant therapy avoided the use of painful postsurgical injection or radiotherapy for the 1–3cm primary ear keloids. The advantages of magnification were better clearance of keloid tissue, easier identification of tract and removal of keloid pseudopods, meticulous suturing, and comfortable elevation of a small local flap. PMID:29731586

Laser and Light-based Treatment of Keloids – A Review

PubMed Central

Mamalis, A.D.; Lev-Tov, H.; Nguyen, D.H.; Jagdeo, J.R.

2015-01-01

Keloids are an overgrowth of fibrotic tissue outside the original boundaries of an injury and occur secondary to defective wound healing. Keloids often have a functional, aesthetic, or psychosocial impact on patients as highlighted by quality-of-life studies. Our goal is to provide clinicians and scientists an overview of the data available on laser and light-based therapies for treatment of keloids, and highlight emerging light-based therapeutic technologies and the evidence available to support their use. We employed the following search strategy to identify the clinical evidence reported in the biomedical literature: in November 2012, we searched PubMed.gov, Ovid MEDLINE, Embase, and Cochrane Reviews (1980-present) for published randomized clinical trials, clinical studies, case series, and case reports related to the treatment of keloids. The search terms we utilized were ‘keloid(s)’ AND ‘laser’ OR ‘light-emitting diode’ OR ‘photodynamic therapy’ OR ‘intense pulsed light’ OR ‘low level light’ OR ‘phototherapy.’ Our search yielded 347 unique articles. Of these, 33 articles met our inclusion and exclusion criteria. We qualitatively conclude that laser and light-based treatment modalities may achieve favorable patient outcomes. Clinical studies using CO2 laser are more prevalent in current literature and a combination regimen may be an adequate ablative approach. Adding light-based treatments, such as LED phototherapy or photodynamic therapy, to laser treatment regimens may enhance patient outcomes. Lasers and other light-based technology have introduced new ways to manage keloids that may result in improved aesthetic and symptomatic outcomes and decreased keloid recurrence. PMID:24033440

Protein-protein interaction network of gene expression in the hydrocortisone-treated keloid.

PubMed

Chen, Rui; Zhang, Zhiliang; Xue, Zhujia; Wang, Lin; Fu, Mingang; Lu, Yi; Bai, Ling; Zhang, Ping; Fan, Zhihong

2015-01-01

In order to explore the molecular mechanism of hydrocortisone in keloid tissue, the gene expression profiles of keloid samples treated with hydrocortisone were subjected to bioinformatics analysis. Firstly, the gene expression profiles (GSE7890) of five samples of keloid treated with hydrocortisone and five untreated keloid samples were downloaded from the Gene Expression Omnibus (GEO) database. Secondly, data were preprocessed using packages in R language and differentially expressed genes (DEGs) were screened using a significance analysis of microarrays (SAM) protocol. Thirdly, the DEGs were subjected to gene ontology (GO) function and KEGG pathway enrichment analysis. Finally, the interactions of DEGs in samples of keloid treated with hydrocortisone were explored in a human protein-protein interaction (PPI) network, and sub-modules of the DEGs interaction network were analyzed using Cytoscape software. Based on the analysis, 572 DEGs in the hydrocortisone-treated samples were screened; most of these were involved in the signal transduction and cell cycle. Furthermore, three critical genes in the module, including COL1A1, NID1, and PRELP, were screened in the PPI network analysis. These findings enhance understanding of the pathogenesis of the keloid and provide references for keloid therapy. © 2015 The International Society of Dermatology.

Postoperative Strontium-90 Brachytherapy in the Prevention of Keloids: Results and Prognostic Factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viani, Gustavo A.; Stefano, Eduardo J.; Afonso, Sergio L.

2009-04-01

Purpose: The aim of this study was to evaluate the results of keloidectomy and strontium 90 brachytherapy in the prevention of keloid recurrence following excision and to identify outcome and the prognostic factors that predict keloid recurrence after irradiation. Methods and Materials: Data of 612 patients with 892 keloids treated between 1992 and 2006 were evaluated retrospectively. Brachytherapy was performed using a Sr-90Y surface applicator. Total dose was 20 Gy in 10 fractions. Results: With a median follow-up of 61 months, the overall recurrence-free response rate for all keloids was 87.6%. Multivariate analysis revealed the following prognostic factors for recurrence:more » keloid size > 5 cm (p < 0.0001), burn scars as the keloid etiology (p < 0.0001), and previous treatment (p < 0.0001). Outcome was not found to be significantly related to the interval between surgery and radiotherapy, sex, or age. Pruritus and skin reddening were the most common symptoms of keloids, but all signs and symptoms abated with time after treatment. Cosmetic results from the keloid treatment were considered good or excellent in 70.6% of the patients. Conclusion: Our study findings show that excision plus Sr-90 brachytherapy is effective in the eradication of keloids. Sr-90 radiotherapy (20 Gy in 10 fractions) achieved a similar local control rate, as have higher doses per fraction in other series. It also resulted in a good cosmetic rate and relief of symptoms. Our data further suggest that the initiation of postoperative irradiation within hours of surgical excision is not important to therapeutic outcome.« less

Postoperative strontium-90 brachytherapy in the prevention of keloids: results and prognostic factors.

PubMed

Viani, Gustavo A; Stefano, Eduardo J; Afonso, Sergio L; De Fendi, Ligia I

2009-04-01

The aim of this study was to evaluate the results of keloidectomy and strontium 90 brachytherapy in the prevention of keloid recurrence following excision and to identify outcome and the prognostic factors that predict keloid recurrence after irradiation. Data of 612 patients with 892 keloids treated between 1992 and 2006 were evaluated retrospectively. Brachytherapy was performed using a Sr-90Y surface applicator. Total dose was 20 Gy in 10 fractions. With a median follow-up of 61 months, the overall recurrence-free response rate for all keloids was 87.6%. Multivariate analysis revealed the following prognostic factors for recurrence: keloid size > 5 cm (p < 0.0001), burn scars as the keloid etiology (p < 0.0001), and previous treatment (p < 0.0001). Outcome was not found to be significantly related to the interval between surgery and radiotherapy, sex, or age. Pruritus and skin reddening were the most common symptoms of keloids, but all signs and symptoms abated with time after treatment. Cosmetic results from the keloid treatment were considered good or excellent in 70.6% of the patients. Our study findings show that excision plus Sr-90 brachytherapy is effective in the eradication of keloids. Sr-90 radiotherapy (20 Gy in 10 fractions) achieved a similar local control rate, as have higher doses per fraction in other series. It also resulted in a good cosmetic rate and relief of symptoms. Our data further suggest that the initiation of postoperative irradiation within hours of surgical excision is not important to therapeutic outcome.

Clinical implications of single- versus multiple-site keloid disorder: a retrospective study in an Asian population.

PubMed

Park, Tae Hwan; Park, Ji Hae; Tirgan, Michael H; Halim, Ahmad Sukari; Chang, Choong Hyun

2015-02-01

There is strong evidence of genetic susceptibility in individuals with keloid disorder. The purpose of this cross-sectional study was to determine the clinical relevance of our proposed variables on the multiplicity of keloids by further investigating the presence of other keloids and a family history. This was a retrospective review, using institutional review board-approved questionnaires, of patients with keloids who were seen at Kangbuk Samsung Hospital between December 2002 and February 2010. Eight hundred sixty-eight patients were included in our study. Comparisons between the 2 groups were made using Mann-Whitney tests for continuous variables and χ2 tests for categorical variables. In our patient group, younger age of onset and the presence of family history were significantly associated with the occurrence of keloids at multiple sites. The locations of extra-auricular keloids, in order of frequency, included the shoulder; anterior chest, including the breasts; deltoid; trunk and pubic area; upper extremities; lower extremities; and other sites. As compared to secondary keloids, primary keloids were significantly associated with both a lower degree of recurrence and the presence of other keloids. The presence or absence of family history was significantly associated with the presence or absence of other keloids and primary or secondary keloids. Keloid disorder is one of the most frustrating problems in wound healing and advances in our understanding of the differences of occurrence at a single site versus multiple sites might help in understanding pathogenesis and improving treatment.

Antiproliferative effect of methanolic extraction of tualang honey on human keloid fibroblasts

PubMed Central

2011-01-01

Background Keloid is a type of scar which extends beyond the boundaries of the original wound. It can spread to the surrounding skin by invasion. The use of Tualang honey is a possible approach for keloid treatment. The objective of this study was to determine the antiproliferative effect of methanolic extraction of Tualang honey to primary human keloid fibroblasts and to identify the volatile compounds in methanol extraction of Tualang honey. Methods Crude Tualang honey was extracted with methanol and then dried using rota vapor to remove remaining methanol from honey. Normal and keloid fibroblasts were verified and treated with the extracted honey. Cell proliferation was tested with [3-(4,5-dimethylthiazol-2-yi)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] (MTS) assay. Extraction of Tualang honey using methanol was carried out and the extracted samples were analysed using gas chromatography-mass spectrometry (GC-MS). The result was analysed using SPSS and tested with Kruskal-Wallis and Mann-Whitney tests. Results Methanolic extraction of honey has positive anti proliferative effect on keloid fibroblasts in a dose-dependent manner. The presence of fatty acids such as palmitic acid, stearic acid, oleic acid, linoleic acid and octadecanoic acid may contribute to the anti-proliferative effect in keloid fibroblasts. Conclusions The methanolic honey extraction has an antiproliferative effect on keloid fibroblasts and a range of volatile compounds has been identified from Tualang honey. The antiproliferative effect of keloid fibroblasts towards Tualang honey may involve cell signaling pathway. Identifying other volatile compounds from different organic solvents should be carried out in future. PMID:21943200

Recent Developments in the Use of Intralesional Injections Keloid Treatment

PubMed Central

Trisliana Perdanasari, Aurelia; Lazzeri, Davide; Su, Weijie; Xi, Wenjing; Zheng, Zhang; Ke, Li; Min, Peiru; Feng, Shaoqing; Persichetti, Paolo

2014-01-01

Keloid scars are often considered aesthetically unattractive and frustrating problems that occur following injuries. They cause functional and cosmetic deformities, displeasure, itching, pain, and psychological stress and possibly affect joint movement. The combination of these factors ultimately results in a compromised quality of life and diminished functional performance. Various methods have been implemented to improve keloid scars using both surgical and non-surgical approaches. However, it has proven to be a challenge to identify a universal treatment that can deliver optimal results for all types of scars. Through a PubMed search, we explored most of the literature that is available about the intralesional injection treatment of hypertrophic scars and keloids and highlights both current (corticosteroid, 5-fluorouracil, bleomycin, interferon, cryotherapy and verapamil) and future treatments (interleukin-10 and botulinum toxin type A). The reference lists of retrieved articles were also analysed. Information was gathered about the mechanism of each injection treatment, its benefits and associated adverse reactions, and possible strategies to address adverse reactions to provide reliable guidelines for determining the optimal treatment for particular types of keloid scars. This article will benefit practitioners by outlining evidence-based treatment strategies using intralesional injections for patients with hypertrophic scars and keloids. PMID:25396172

Treatment of keloid scars with a 1210-nm diode laser in an animal model.

PubMed

Philandrianos, Cécile; Bertrand, Baptiste; Andrac-Meyer, Lucile; Magalon, Guy; Casanova, Dominique; Kerfant, Nathalie; Mordon, Serge

2015-12-01

A temperature increase can improve wound healing by activation of heat shock protein 70 and stimulation of fibroblasts. Since keloids are a dysfunction of collagen fiber synthesis and organization, this study aimed to evaluate if a 1,210 nm diode laser could have effects in a new animal model of keloid scars. A total of 39 nude mice were used for this study. Phototypes IV and V human keloids were grafted into their backs and after 1 month of healing, the mice were divided into four groups: Control, Laser, Resection, Resection/Laser. In the Laser group, the keloids were treated with a 1,210-nm diode-laser with the following parameters: 4 W; 10 seconds; fluence: 51 J/cm(2) ; spot: 18.9 × 3.7 mm(2) . In the Resection group, surgical intra-lesional excision was performed. In the Resection/Laser group, keloids were treated with the 1,210-nm laser-diode after surgical intra-lesional excision. Temperature measurements were made during the laser treatment. Clinical examination and histological study were performed on the day of treatment and 1 month, 2 months, and 3 months later. Mean temperature measurement was of 44.8°C (42-48°) in the Laser groups. No healing complications or keloid proliferation was observed in any group. Keloid histologic characters were confirmed in all grafts. No histologic particularity was observed in the laser groups in comparison with the Control and Resection groups. First, this keloid animal model appears to be adapted for laser study. Secondly, the 1,210-nm diode laser does not induce keloid thermal damage in vivo. Further studies with different 1,210-nm laser diode parameters should be performed in order to observe significant effects on keloids. © 2015 Wiley Periodicals, Inc.

Early postoperative magnet application combined with hydrocolloid dressing for the treatment of earlobe keloids.

PubMed

Park, Tae Hwan; Chang, Choong Hyun

2013-04-01

To prevent the recurrence of earlobe keloids after surgical removal, a reliable and safe postoperative treatment method is critical. To the authors' knowledge, no studies have elucidated the most effective postoperative dressing method for preventing the recurrence of earlobe keloids. This study aimed to compare keloid recurrence rates in patients whose keloids were dressed using conventional methods (plain gauze or a polyvinyl alcohol sponge) with those of a matched cohort of patients whose keloids were dressed using magnets combined with hydrocolloid materials. This observational case-control study compared a retrospective cohort of patients whose keloids were dressed using conventional methods with a matched prospective cohort of patients whose keloids were dressed using magnets combined with hydrocolloid materials. The study included patients with pathologically confirmed earlobe keloids that were surgically excised with primary closure. Patients 8 years of age or older underwent adjuvant pressure therapy with magnets at the study hospital. Patients were excluded from the study if they were unavailable for follow-up evaluation, if they had received additional adjuvant therapy during treatment, or if histologic confirmation of a keloid was not obtained. Matched-pair analysis was performed using the McNemar test. Treatment outcome was evaluated as recurrence or nonrecurrence. Overall, 9 (11.2%) of the 80 study patients experienced recurrence. The recurrence rate was significantly lower in the matched case group (2 of 40, 5%) than in the matched control group (7 of 40, 17.5%) during the follow-up period of 18 months (p=0.0253). The authors' novel dressing of magnets and hydrocolloid materials appears to be effective in reducing earlobe keloid recurrence. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to

Histomorphometric analysis of collagen architecture of auricular keloids in an Asian population.

PubMed

Chong, Yosep; Park, Tae Hwan; Seo, Sang won; Chang, Choong Hyun

2015-03-01

Keloids are a pathologic condition of the reparative process, which present as excessive scar formation that involves various cells and cytokines. Many studies focusing on the histologic feature of keloids, however, have shown discordant results without consideration of architectural aspect of collagen structure. The purpose of this study was to demonstrate a schematic illustration of collagen architecture of keloids, specifically auricular keloids, and to analyze each part on the histomorphologic and morphometric basis. Thirty-nine surgically excised auricular keloids were retrieved from the file of Kangbuk Samsung Hospital. After exhaustive histomorphologic analysis, 3 distinctive structural parts, keloidal collagen, organizing collagen, and proliferating core collagen, were identified and mapped in every case. Cellularity of fibroblasts, blood vessel density, degree of inflammatory cell infiltration, and mast cells counts using Masson trichrome stain, Van Gieson stain, toluidine blue stain, and immunohistochemical stains for CD31 and smooth muscle actin were analyzed in each part of each case. Morphometric analysis on these parameters using ImageJ software was performed using 3 representative images of each part. Three parts were histomorphologically distinct by shape and array of collagen bundles, fibroblasts cellularity, blood vessel density, degree of inflammatory cells, and mast cell infiltration. Morphometric analysis revealed statistically significant difference between each part in fibroblasts cellularity, blood vessel density, degree of inflammatory cell infiltration, and mast cells count. All parameters were exceedingly high in whorling hypercellular fibrous nodules in proliferating core collagen showing simultaneous changes in other parts. Morphologically and morphometrically, 3 distinctive parts were identified in auricular keloids. Mast cell infiltrations, blood vessel density, and fibroblast cellularity are simultaneously increased or decreased

Involvement of upper torso stress amplification, tissue compression and distortion in the pathogenesis of keloids.

PubMed

Bux, Shamin; Madaree, Anil

2012-03-01

Keloids are benign tumours composed of fibrous tissue produced during excessive tissue repair triggered by minor injury, trauma or surgical incision. Although it is recognized that keloids have a propensity to form in the upper torso of the body, the predisposing factors responsible for this have not been investigated. It is crucial that the aetiopathoical factors implicated in keloid formation be established to provide guidelines for well-informed more successful treatment. We compared keloid-prone and keloid-protected skin, identified pertinent morphological differences and explored how inherent structural characteristics and intrinsic factors may promote keloid formation. It was determined that keloid prone areas were covered with high tension skin that had low stretch and a low elastic modulus when compared with skin in keloid protected areas where the skin was lax with a high elastic modulus and low pre-stress level. Factors contributing to elevated internal stress in keloid susceptible skin were the protrusion of hard connective tissue such as bony prominences or cartilage into the dermis of skin as well as inherent skin characteristics such as the bundled arrangement of collagen in the reticular dermis, the existent high tension, the low elastic modulus, low stretch ability, contractile forces exerted by wound healing fibroblastic cells and external forces. Stress promotes keloid formation by causing dermal distortion and compression which subsequently stimulate proliferation and enhanced protein synthesis in wound healing fibroblastic cells. The strain caused by stress also compresses and occludes microvessels causing ischaemic effects and reperfusion injury which stimulate growth when blood rich in growth factors returns to the tissue. The growth promoting effects of increased internal stress, primarily, and growth factors released by reperfusing blood, manifest in keloid formation. Other inherent skin characteristics promoting keloid growth during the

Efficacy of custom-made pressure clips for ear keloid treatment after surgical excision.

PubMed

Tanaydin, V; Beugels, J; Piatkowski, A; Colla, C; van den Kerckhove, E; Hugenholtz, G C G; van der Hulst, R R

2016-01-01

Mechanical pressure is increasingly applied as a means to prevent or treat keloid scars. The aim of this study is to analyze the long-term efficacy of our custom-molded pressure-adjustable earclips to prevent keloid recurrence after surgical excision. Using our custom-molded earclip, 88 patients who had undergone ear surgery for keloid scars were treated for 12 h a day for 6-18 months. The mean follow-up was 6.5 years. The primary outcome was the recurrence of keloids with patient satisfaction being the secondary outcome as assessed by Patient and Observer Scale (POSAS). Keloid scars did not recur in 70.5% of treated patients. The Fitzpatrick scale, which classifies human skin by type, was significantly different between the recurrence and nonrecurrence group. Differences in other patient characteristics were not found between both groups. All parameters mentioned in the POSAS patient scale drastically improved after therapy. There were no severe side effects observed after the therapy. Our pressure-adjustable earclip model is an effective tool in the prevention of ear keloid recurrence and is associated with high patient satisfaction. Its benefits should prompt further studies on its value as an adjuvant therapy to surgery in keloid treatment. Level III on the Evidence Rating Scale for Therapeutic Studies. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Healed corneal ulcer with keloid formation.

PubMed

Alkatan, Hind M; Al-Arfaj, Khalid M; Hantera, Mohammed; Al-Kharashi, Soliman

2012-04-01

We are reporting a 34-year-old Arabic white female patient who presented with a white mass covering her left cornea following multiple ocular surgeries and healed corneal ulcer. The lesion obscured further view of the iris, pupil and lens. The patient underwent penetrating keratoplasty and the histopathologic study of the left corneal button showed epithelial hyperplasia, absent Bowman's layer and subepithelial fibrovascular proliferation. The histopathologic appearance was suggestive of a corneal keloid which was supported by further ultrastructural study. The corneal graft remained clear 6 months after surgery and the patient was satisfied with the visual outcome. Penetrating keratoplasty may be an effective surgical option for corneal keloids in young adult patients.

Unfolded protein response regulation in keloid cells.

PubMed

Butler, Paris D; Wang, Zhen; Ly, Daphne P; Longaker, Michael T; Koong, Albert C; Yang, George P

2011-05-01

Keloids are a common form of pathologic wound healing characterized by excessive production of extracellular matrix. The unfolded protein response (UPR) is a cellular response to hypoxia, a component of the wound microenvironment, capable of protecting cells from the effects of over-accumulation of misfolded proteins. Since keloids have hypersecretion of extracellular matrix, we hypothesized that keloid fibroblasts (KFs) may have enhanced activation of the UPR compared with normal fibroblasts (NFs). KFs and NFs were placed in a hypoxia chamber for 0, 24, and 48h. We also used tunicamycin to specifically up-regulate the UPR. UPR activation was assayed by PCR for xbp-1 splicing and by immunoblotting with specific antibodies for the three UPR transducers. Nuclear localization of XBP-1 protein in KFs was confirmed by immunofluorescence. There is increased activation of XBP-1 protein in KFs compared with NFs following exposure to hypoxia. Pancreatic ER kinase (PERK) and ATF-6, two other pathways activated by the UPR, show comparable activation between KFs and NFs. We confirmed that there is enhanced activation of XBP-1 by demonstrating increased nuclear localization of XBP-1 using immunofluorescence. In contrast to our initial hypothesis that keloids would have broad activation of the UPR, we demonstrate here that there is a specific up-regulation of one facet of the UPR response. This may represent a specific molecular defect in KFs compared with NFs, and also suggests modulation of the UPR can be used in wound healing therapy. Published by Elsevier Inc.

Dose-Effect Relationships for Recurrence of Keloid and Pterygium After Surgery and Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kal, Henk B.; Veen, Ronald E.; Juergenliemk-Schulz, Ina M.

2009-05-01

Purpose: To show radiation dose-response relationships for recurrence of keloid and pterygium after radiotherapy following surgery. Methods and Materials: Using PubMed, we performed a retrospective review of articles reporting incidences and/or dose-response relationships for recurrence of keloid and pterygium after radiotherapy following surgery. The irradiation regimens identified were normalized by use of the linear-quadratic model; biologically effective doses (BEDs) were calculated. Results: For keloid recurrence after radiotherapy following keloid removal, with either teletherapy or brachytherapy, the recurrence rate after having delivered a BED greater than 30 Gy is less than 10%. For pterygium recurrence after bare sclera surgery and {supmore » 90}Sr {beta}-irradiation, a BED of about 30 Gy seems to be sufficient also to reduce the recurrence rate to less than 10%. Conclusions: Most of the doses in the radiotherapy schemes used for prevention of keloid recurrence after surgery are too low. In contrast, the doses applied in most regimens to prevent pterygium recurrence are too high. A scheme with a BED of 30 to 40 Gy seems to be sufficient to prevent recurrences of keloid as well as pterygium.« less

Reduced Dermatopontin Expression Is a Molecular Link Between Uterine Leiomyomas and Keloids

PubMed Central

Catherino, William H.; Leppert, Phyllis C.; Stenmark, Matthew H.; Payson, Mark; Potlog-Nahari, Clariss; Nieman, Lynnette K.; Segars, James H.

2014-01-01

Uterine leiomyomas are prevalent estrogen-responsive clonal tumors, but the specific genetic alterations that contribute to their development have not been elucidated. To identify genes involved in the formation of leiomyomas, we used global expression profiling to compare clonal tumors with normal myometrium. Contrary to expectation, genes involved in estrogen action were not differentially expressed between leiomyoma and normal myometrium. Genes encoding extracellular-matrix proteins were prominently featured, suggesting their involvement in formation of a myofibroblast phenotype. Analysis of the extracellular matrix in the leiomyomas revealed a disordered collagen fibril orientation. Expression of the collagen-binding protein dermatopontin was found to be consistently decreased in leiomyoma by both reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR (mean underexpression = 9.41-fold) regardless of leiomyoma size, leiomyoma location, patient race, and patient age. This expression pattern was observed in 11 subjects and a total of 23 leiomyoma: myometrium pairs. Decreased expression of dermatopontin was also associated with keloid formation, a fibrotic disease that shares epidemiologic similarities with leiomyoma. Immunohistochemical studies of leiomyomas and keloids demonstrated reduced levels of dermatopontin in both tissues. In addition, ultrastructural analysis revealed that the orientation of the collagen fibrils in the keloid tissues strongly resembled that in the leiomyomas. Reduction in dermatopontin was associated with an increase in transforming growth factor–β3 (TGFB3) mRNA levels in leiomyomas, whereas other genes involved in dermatopontin signaling were not differentially expressed. These findings suggest that leiomyoma development involves a myofibroblast cell phenotype characterized by dysregulation of genes encoding extracellular-matrix proteins. In particular, decreased expression of dermatopontin represents a

Recent Understandings of Biology, Prophylaxis and Treatment Strategies for Hypertrophic Scars and Keloids

PubMed Central

Jang, Yong Ju

2018-01-01

Hypertrophic scars and keloids are fibroproliferative disorders that may arise after any deep cutaneous injury caused by trauma, burns, surgery, etc. Hypertrophic scars and keloids are cosmetically problematic, and in combination with functional problems such as contractures and subjective symptoms including pruritus, these significantly affect patients’ quality of life. There have been many studies on hypertrophic scars and keloids; but the mechanisms underlying scar formation have not yet been well established, and prophylactic and treatment strategies remain unsatisfactory. In this review, the authors introduce and summarize classical concepts surrounding wound healing and review recent understandings of the biology, prevention and treatment strategies for hypertrophic scars and keloids. PMID:29498630

Noninvasive treatment of keloid using customized Re-188 skin patch.

PubMed

Bhusari, Priya; Shukla, Jaya; Kumar, Munish; Vatsa, Rakhee; Chhabra, Anupriya; Palarwar, Kanchan; Rathore, Yogesh; De, Dipanker; Kumaran, Sendhil; Handa, Sanjeev; Mittal, B R

2017-09-01

Keloids are developed as fibrotic scar at the site of surgery or trauma and often enlarge beyond the original scar margins. Re-188 colloid coated customized patch was superficially fixed onto the lesion for 3 hrs. The same patch was reapplied on the lesion on third day for 3 hrs. The patients were followed up at 1, 3,6 and 12 months post treatment. The size and elevation of the keloid lesion was reduced after treatment. The total radiation dose from the patch (day-1 and day-3) was 100 Gy/mCi of Re-188. The radioactive patch treatment of keloids is noninvasive, painless and safe with prolonged outcome. © 2017 Wiley Periodicals, Inc.

Inhibitory activities of omega-3 Fatty acids and traditional african remedies on keloid fibroblasts.

PubMed

Olaitan, Peter B; Chen, I-Ping; Norris, James E C; Feinn, Richard; Oluwatosin, Odunayo M; Reichenberger, Ernst J

2011-04-01

Keloids develop when scar tissue responds to skin trauma with proliferative fibrous growths that extend beyond the boundaries of the original wound and progress for several months or years. Keloids most frequently occur in individuals of indigenous sub-Saharan African origin. The etiology for keloids is still unknown and treatment can be problematic as patients respond differently to various treatment modalities. Keloids have a high rate of recurrence following surgical excision. Some West African patients claim to have had successful outcomes with traditional African remedies-boa constrictor oil (BCO) and shea butter-leading the authors to investigate their effects on cultured fibroblasts. The effects of emulsions of BCO, fish oil, isolated omega-3 fatty acids, and shea butter were tested in comparison to triamcinolone regarding inhibition of cell growth in keloid and control fibroblast cultures. In a series of controlled studies, it was observed that fish oil and BCO were more effective than triamcinolone, and that cis-5, 8, 11, 14, 17-eicosapentaenoic acid was more effective than -linolenic acid. While cell counts in control cultures continuously decreased over a period of 5 days, cell counts in keloid cultures consistently declined between day 1 and day 3, and then increased between day 3 and day 5 for all tested reagents except for fish oil. These results suggest that oils rich in omega-3 fatty acids may be effective in reducing actively proliferating keloid fibroblasts. Additional studies are warranted to investigate whether oils rich in omega-3 fatty acids offer effective and affordable treatment for some keloid patients, especially in the developing world.

Tissue Inhibitor of Metalloproteinase-2 Suppresses Collagen Synthesis in Cultured Keloid Fibroblasts

PubMed Central

Dohi, Teruyuki; Aoki, Masayo; Ogawa, Rei; Akaishi, Satoshi; Shimada, Takashi; Okada, Takashi; Hyakusoku, Hiko

2015-01-01

Background: Keloids are defined as a kind of dermal fibroproliferative disorder resulting from the accumulation of collagen. In the remodeling of extracellular matrix, the balance between matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) is as critical as the proper production of extracellular matrix. We investigate the role of TIMPs and MMPs in the pathogenesis of keloids and examine the therapeutic potential of TIMP-2. Methods: The expression of TIMPs and MMPs in most inflamed parts of cultured keloid fibroblasts (KFs) and peripheral normal skin fibroblasts (PNFs) in the same individuals and the reactivity of KFs to cyclic mechanical stretch were analyzed by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (n = 7). To evaluate the effect of treating KFs with TIMP-2, collagen synthesis was investigated by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, and microscopic analysis was used to examine the treatment effects of TIMP-2 on ex vivo cultures of keloid tissue (n = 6). Results: TIMP-2 was downregulated in cultured KFs compared with PNFs in the same individuals, and the reduction in TIMP-2 was exacerbated by cyclic mechanical stretch. Administration of TIMP-2 (200 or 300 ng/mL) significantly suppressed expression of Col1A2 and Col3A1 mRNA and collagen type I protein in KFs. TIMP-2 also significantly reduced the skin dermal and collagen bundle thickness in ex vivo cultures of keloid tissue. Conclusion: These results indicated that downregulation of TIMP-2 in KFs is a crucial event in the pathogenesis of keloids, and the TIMP-2 would be a promising candidate for the treatment of keloids. PMID:26495233

Different properties of skin of different body sites: The root of keloid formation?

PubMed

Butzelaar, Liselotte; Niessen, Frank B; Talhout, Wendy; Schooneman, Dennis P M; Ulrich, Magda M; Beelen, Robert H J; Mink van der Molen, Aebele B

2017-09-01

The purpose of this study was to examine extracellular matrix composition, vascularization, and immune cell population of skin sites prone to keloid formation. Keloids remain a complex problem, posing esthetical as well as functional difficulties for those affected. These scars tend to develop at anatomic sites of preference. Mechanical properties of skin vary with anatomic location and depend largely on extracellular matrix composition. These differences in extracellular matrix composition, but also vascularization and resident immune cell populations might play a role in the mechanism of keloid formation. To examine this hypothesis, skin samples of several anatomic locations were taken from 24 human donors within zero to 36 hours after they had deceased. Collagen content and cross-links were determined through high-performance liquid chromatography. The expression of several genes, involved in extracellular matrix production and degradation, was measured by means of real-time PCR. (Immuno)histochemistry was performed to detect fibroblasts, collagen, elastin, blood vessels, Langerhans cells, and macrophages. Properties of skin of keloid predilections sites were compared to properties of skin from other locations (nonpredilection sites [NPS]). The results indicated that there are site specific variations in extracellular matrix properties (collagen and cross-links) as well as macrophage numbers. Moreover, predilection sites (PS) for keloid formation contain larger amounts of collagen compared to NPS, but decreased numbers of macrophages, in particular classically activated CD40 positive macrophages. In conclusion, the altered (histological, protein, and genetic) properties of skin of keloid PS may cause a predisposition for and contribute to keloid formation. © 2017 by the Wound Healing Society.

Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis.

PubMed

Ogawa, Rei

2017-03-10

Keloids and hypertrophic scars are caused by cutaneous injury and irritation, including trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster infection. Notably, superficial injuries that do not reach the reticular dermis never cause keloidal and hypertrophic scarring. This suggests that these pathological scars are due to injury to this skin layer and the subsequent aberrant wound healing therein. The latter is characterized by continuous and histologically localized inflammation. As a result, the reticular layer of keloids and hypertrophic scars contains inflammatory cells, increased numbers of fibroblasts, newly formed blood vessels, and collagen deposits. Moreover, proinflammatory factors, such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α are upregulated in keloid tissues, which suggests that, in patients with keloids, proinflammatory genes in the skin are sensitive to trauma. This may promote chronic inflammation, which in turn may cause the invasive growth of keloids. In addition, the upregulation of proinflammatory factors in pathological scars suggests that, rather than being skin tumors, keloids and hypertrophic scars are inflammatory disorders of skin, specifically inflammatory disorders of the reticular dermis. Various external and internal post-wounding stimuli may promote reticular inflammation. The nature of these stimuli most likely shapes the characteristics, quantity, and course of keloids and hypertrophic scars. Specifically, it is likely that the intensity, frequency, and duration of these stimuli determine how quickly the scars appear, the direction and speed of growth, and the intensity of symptoms. These proinflammatory stimuli include a variety of local, systemic, and genetic factors. These observations together suggest that the clinical differences between keloids and hypertrophic scars merely reflect differences in the intensity, frequency, and duration of

Inhibitory Activities of Omega-3 Fatty Acids and Traditional African Remedies on Keloid Fibroblasts

PubMed Central

Olaitan, Peter B.; Chen, I-Ping; Norris, James E.C.; Feinn, Richard; Oluwatosin, Odunayo M.; Reichenberger, Ernst J.

2012-01-01

Keloids develop when scar tissue responds to skin trauma with proliferative fibrous growths that extend beyond the boundaries of the original wound and progress for several months or years. Keloids most frequently occur in individuals of indigenous sub-Saharan African origin. The etiology for keloids is still unknown and treatment can be problematic as patients respond differently to various treatment modalities. Keloids have a high rate of recurrence following surgical excision. Some West African patients claim to have had successful outcomes with traditional African remedies—boa constrictor oil (BCO) and shea butter—leading the authors to investigate their effects on cultured fibroblasts. The effects of emulsions of BCO, fish oil, isolated omega-3 fatty acids, and shea butter were tested in comparison to triamcinolone regarding inhibition of cell growth in keloid and control fibroblast cultures. In a series of controlled studies, it was observed that fish oil and BCO were more effective than triamcinolone, and that cis-5, 8, 11, 14, 17-eicosapentaenoic acid was more effective than -linolenic acid. While cell counts in control cultures continuously decreased over a period of 5 days, cell counts in keloid cultures consistently declined between day 1 and day 3, and then increased between day 3 and day 5 for all tested reagents except for fish oil. These results suggest that oils rich in omega-3 fatty acids may be effective in reducing actively proliferating keloid fibroblasts. Additional studies are warranted to investigate whether oils rich in omega-3 fatty acids offer effective and affordable treatment for some keloid patients, especially in the developing world. PMID:24489452

Keloid scar harbouring malignant blue naevus emphasises the need for excision biopsy and routine histology.

PubMed

Theopold, C; Pritchard, S; McGrouther, D A; Bayat, A

2009-01-01

We report the finding of a malignant blue naevus of 14.3 mm Breslow thickness in association with a keloid scar on the earlobe of an Afrocaribbean gentleman. Malignant blue naevus is extremely rare and to date it has not been reported in association with keloid scars. We recommend routine histopathological examination of all excised keloid scars. Where histopathological services are limited, examination should certainly be carried out for keloids with unusual characteristics. Excision should be complete, rather than intralesional, in order to avoid leaving behind areas of potential neoplasia.

Use of silicone gel sheets for prevention of keloid scars after median sternotomy.

PubMed

Sakuraba, Motoki; Takahashi, Nobumasa; Akahoshi, Taku; Miyasaka, Yoshikazu; Suzuki, Kenji

2011-04-01

A keloid scar often appears at the incision site of patients after median sternotomy. Use of silicone gel to treat hypertrophic burn scars and fresh incisions has yielded encouraging results. In this study, we report our experience with the preventive use of silicone gel sheets for keloid scars after median sternotomy. Nine patients who underwent a median sternotomy were studied. A silicone gel sheet was kept directly on the surgical incision for 24 h starting 2 weeks after surgery. The treatment was repeated with a new sheet every 4 weeks for 24 weeks, at which times the subjective symptoms and the changes in keloid scars were determined. None of the patients experienced an aggravation of any subjective symptoms during the 24-week study. After 24 weeks, all patients were free of a keloid scar that showed a rise and contraction of skin and causes discomfort. No adverse events were reported by any of the patients. A silicone gel sheet is safe and effective for the preventing the formation of keloid scars after median sternotomy.

Treatment of retroauricular keloids: Revision of cases treated at the ENT service of HC/UFPR.

PubMed

Carvalho, Bettina; Ballin, Annelyse Cristine; Becker, Renata Vecentin; Ribeiro, Talita Beithum; Cavichiolo, Juliana Benthien; Ballin, Carlos Roberto; Mocellin, Marcos

2012-04-01

 Keloids are benign tumors arising from abnormal healing of the skin, and there are several procedures available for their treatment.  The objective of this study was to evaluate the outcomes of patients undergoing treatment of keloids after ear, nose, and throat (ENT) surgeries at our service center.  We conducted thorough, retrospective and prospective analysis of records of patients undergoing treatment of retroauricular keloids at our center.  Nine patients were evaluated, and 6 underwent resection and adjuvant beta-therapy, 2 underwent resection with local application of corticosteroids, and only 1 underwent resection without adjuvant therapy. There was no recurrence of keloids in patients that were treated with beta-therapy in the early postoperative period. One patient had relapsed despite corticosteroid administration and late beta-therapy.  Several techniques have been used for the treatment of retroauricular keloids, and beta-therapy is thought to yield the best results, followed by the use of intralesional corticosteroids.  Treatment of retroauricular keloids remains a challenge. While new techniques are being developed, resection followed by early beta-therapy is still the best treatment option.

Keloids in rural black South Africans. Part 2: dietary fatty acid intake and total phospholipid fatty acid profile in the blood of keloid patients.

PubMed

Louw, L; Dannhauser, A

2000-11-01

In the second part of this study, emphasis is placed on nutritional intakes (fatty acids and micronutrients) and fatty acid intake and metabolism in the blood, respectively, according to a combined 24 h recall and standardized food frequency questionnaire analyses of keloid prone patients (n=10), compared with normal black South Africans (n=80), and total phospholipid blood (plasma and red blood cell ) analyses of keloid patients (n=20), compared with normal individuals (n=20). Lipid extraction and fractionation by standard procedures, total phospholipid (TPL) separation with thin layer chromatography, and fatty acid methyl ester analyses with gas liquid chromatography techniques were used. Since nutrition may play a role in several disease disorders, the purpose of this study was to confirm or refute a role for essential fatty acids (EFAs) in the hypothesis of keloid formations stated in part 1 of this study. (1)According to the Canadian recommendation (1991), we observed that in keloid patients linoleic acid (LA) and arachidonic acid (AA) dietary intakes, as EFAs of the omega-6-series, are higher than the recommended 7-11 g/d. However, the a-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dietary intakes, as EFAs of the omega-3 series, are lower than the recommendation of 1.1-1.5 g/d. This was also the case in the control group, where a higher dietary intake of the omega-6 fatty acids and a slightly lower dietary intake of the omega-3 fatty acids occurred. Thus, we confirm a high dietary intake of LA (as a product of organ meats, diary products and many vegetable oils) and AA (as a product of meats and egg yolks), as well as lower dietary intakes of ALA (as a product of grains, green leafy vegetables, soy oil, rapeseed oil and linseed), and EPA and DHA (as products of marine oils). Lower micronutrient intakes than the recommended dietary allowances were observed in the keloid group that may influence EFA metabolism and/or collagen

Laser-assisted topical corticosteroid delivery for the treatment of keloids.

PubMed

Park, Ji Hye; Chun, Ji Young; Lee, Jong Hee

2017-04-01

Laser-assisted drug delivery has generated intense interest. The objectives of this study are to evaluate the clinical benefit of laser-assisted corticosteroid delivery and to compare this technique to corticosteroid intralesional injection, a standard treatment for keloids. Patients with keloids on the left shoulder after BCG vaccination were enrolled in this study. The entire lesion was first treated with an ablative fractional erbium-YAG laser. After this treatment, the lesion was divided into two halves. The first half received an intralesional injection of corticosteroid, whereas the second half received topical application of corticosteroids that were occluded for 3 hours. Four treatment sessions were conducted, with treatments occurring once every 6 weeks. Treatment outcomes were evaluated using the Vancouver Scar Scale (VSS). Pain was self-assessed by the patient during the procedure. The mean keloid VSS score before treatment was 8.59 ± 1.23 for the corticosteroid injection site and 8.31 ± 2.09 for the topical site. After treatment, the mean keloid VSS score was decreased on both sides (4.56 ± 1.09 vs 5.02 ± 0.87, respectively, P > 0.05). Patients rated their satisfaction level as "moderate" on both sides. However, the mean pain score was 1.1 out of 10 on the topical side versus 6.1 on the corticosteroid injection site. The combination of ablative fractional laser treatment and topical corticosteroid application is a promising modality for the treatment of keloids. Moreover, this procedure was not associated with any serious adverse reactions or unbearable pain.

Positive response of a recurrent keloid scar to topical methyl aminolevulinate-photodynamic therapy.

PubMed

Nie, Zhuxiang; Bayat, Ardeshir; Behzad, Farhad; Rhodes, Lesley E

2010-12-01

A 36-year-old Caucasian female of Iranian origin presented with a persistently raised dermal lesion under her chin, confirmed histologically to be a keloid scar. There was a 4-year history of a negative response to a range of conventional treatments including topical silicone gel sheets, steroid creams, steroid injections and surgical excision. In view of treatment failure and an in vitro study indicating a positive effect of photodynamic therapy (PDT)on keloid fibroblasts, we treated our patient's lesion with five sessions of methyl aminolevulinate photodynamic therapy (MAL-PDT) over a period of 5 months. Following this treatment regime, her keloid scar had considerably reduced in size and become flattened.The surface of the keloid also became smooth, with attenuation in erythema at the margin as well as an improvement in the colour of the scar, which was better matched to the surrounding skin. There was no recurrence at 1-year follow-up and this treatment resulted in an overall acceptable cosmetic outcome. This case report presents PDT as a potential treatment option for persistent keloid lesions unresponsive to conventional scar modulation therapies and suggests a need for further research in this area.

Treatment of retroauricular keloids: Revision of cases treated at the ENT service of HC/UFPR

PubMed Central

Carvalho, Bettina; Ballin, Annelyse Cristine; Becker, Renata Vecentin; Ribeiro, Talita Beithum; Cavichiolo, Juliana Benthien; Ballin, Carlos Roberto; Mocellin, Marcos

2012-01-01

Summary Introduction: Keloids are benign tumors arising from abnormal healing of the skin, and there are several procedures available for their treatment. Objective: The objective of this study was to evaluate the outcomes of patients undergoing treatment of keloids after ear, nose, and throat (ENT) surgeries at our service center. Method: We conducted thorough, retrospective and prospective analysis of records of patients undergoing treatment of retroauricular keloids at our center. Results: Nine patients were evaluated, and 6 underwent resection and adjuvant beta-therapy, 2 underwent resection with local application of corticosteroids, and only 1 underwent resection without adjuvant therapy. There was no recurrence of keloids in patients that were treated with beta-therapy in the early postoperative period. One patient had relapsed despite corticosteroid administration and late beta-therapy. Discussion: Several techniques have been used for the treatment of retroauricular keloids, and beta-therapy is thought to yield the best results, followed by the use of intralesional corticosteroids. Conclusion: Treatment of retroauricular keloids remains a challenge. While new techniques are being developed, resection followed by early beta-therapy is still the best treatment option. PMID:25991935

Lysine acetylsalicylate decreases proliferation and extracellular matrix gene expression rate in keloid fibroblasts in vitro.

PubMed

Petri, Jean-Bernhard; Haustein, Uwe-Frithjof

2002-01-01

In genetically predisposed individuals keloids are formed as benign collagenous tumors. The purpose of this study was to investigate whether the proliferation and matrix gene expression of keloid fibroblasts is differently influenced by the anti-inflammatory active drug lysine acetylsalicylate (LAS) when compared to normal skin fibroblasts in vitro. Normal skin and keloid fibroblasts derived from human donors were compared. Excessive scarring and the formation of keloids are (at least in part) due to an overproduction of collagen types I and III. The results show a significant dose-dependent anti-proliferative effect of lysine acetylsalicylate. At the level of gene expression we observed a pronounced inhibitory effect of LAS on procollagen I and III mRNA synthesis, whereas matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 were not altered. Further clinical studies are planned to evaluate these effects of a high-dose treatment of keloids with LAS.

Serum-free keloid fibroblast cell culture: an in vitro model for the study of aberrant wound healing.

PubMed

Koch, R J; Goode, R L; Simpson, G T

1997-04-01

The purpose of this study was to develop an in vitro serum-free keloid fibroblast model. Keloid formation remains a problem for every surgeon. Prior evaluations of fibroblast characteristics in vitro, especially those of growth factor measurement, have been confounded by the presence of serum-containing tissue culture media. The serum itself contains growth factors, yet has been a "necessary evil" to sustain cell growth. The design of this study is laboratory-based and uses keloid fibroblasts obtained from five patients undergoing facial (ear lobule) keloid removal in a university-affiliated clinic. Keloid fibroblasts were established in primary cell culture and then propagated in a serum-free environment. The main outcome measures included sustained keloid fibroblast growth and viability, which was comparable to serum-based models. The keloid fibroblast cell cultures exhibited logarithmic growth, sustained a high cellular viability, maintained a monolayer, and displayed contact inhibition. Demonstrating model consistency, there was no statistically significant difference between the mean cell counts of the five keloid fibroblast cell lines at each experimental time point. The in vitro growth of keloid fibroblasts in a serum-free model has not been done previous to this study. The results of this study indicate that the proliferative characteristics described are comparable to those of serum-based models. The described model will facilitate the evaluation of potential wound healing modulators, and cellular effects and collagen modifications of laser resurfacing techniques, and may serve as a harvest source for contaminant-free fibroblast autoimplants. Perhaps its greatest utility will be in the evaluation of endogenous and exogenous growth factors.

Intralesional excision with topical intralesional cryotherapy improves the treatment of keloid scarring in a paediatric patient.

PubMed

Reissis, D; Tickunas, T; Agha, R A; Greig, Avh

2017-11-01

Recurrent keloid scarring has a significant impact on quality of life. Management is complex, particularly for scars resistant to conventional treatments and in paediatric cases where radiotherapy is not a suitable adjunct to surgical excision. We present the case of a nine-year-old African Caribbean girl with multiple large and recurrent keloid scars on both ears and bilateral sensorineural deafness. Following repeated intralesional excisions, corticosteroid and botulinum toxin injections, she continued to experience rapid recurrence of her keloids, worsening pain and pruritus. She was no longer able to wear her hearing aids because of the large size of the keloids. We employed a novel technique using topical intralesional cryotherapy, applying liquid nitrogen intraoperatively to the inside of the skin flaps immediately post-intralesional keloid excision and before wound closure. At 26-month follow-up a good aesthetic and symptomatic result was achieved, with minimal hypopigmentation, significantly reduced scar volume and significantly slowed recurrence. We discuss this case and review the current literature on the use of topical intralesional cryotherapy for keloid scarring.

Radiotherapy in the management of keloids. Clinical experience with electron beam irradiation and comparison with X-ray therapy.

PubMed

Maarouf, Mohammad; Schleicher, Ursula; Schmachtenberg, Axel; Ammon, Jürgen

2002-06-01

Aim of this study was to evaluate the advantages of electron beam irradiation compared to kilovoltage X-ray therapy in the treatment of keloids. Furthermore, the risk of developing malignancy following keloid radiotherapy was assessed. An automatic water phantom was used to evaluate the dose distribution in tissue. Furthermore, a series of measurements was done on the patients using thermoluminescence dosimeters (TLD) to estimate the doses absorbed by the organs at risk. We also report our clinical experience with electron beam radiation of 134 keloids following surgical excision. Electron beam irradiation offers a high control rate (84%) with minimal side effects for keloids. Electron irradiation provides better dose distribution in tissue, and therefore less radiation burden to the organs at risk. After a mean follow-up period of 7.2 years, no severe side effects or malignancies were observed after keloid radiotherapy. Electron radiation therapy is superior to kilovoltage irradiation for treating keloids due to better dose distribution in tissue. In agreement with the literature, no cases of malignancy were observed after keloid irradiation.

Blue light-irradiated human keloid fibroblasts: an in vitro study

NASA Astrophysics Data System (ADS)

Magni, Giada; Rossi, Francesca; Tatini, Francesca; Pini, Roberto; Coppi, Elisabetta; Cherchi, Federica; Fusco, Irene; Pugliese, Anna Maria; Pedata, Felicita; Fraccalvieri, Marco; Gasperini, Stefano; Pavone, Francesco S.; Tripodi, Cristina; Alfieri, Domenico; Targetti, Lorenzo

2018-02-01

Blue LED light irradiation is currently under investigation because of its effect in wound healing improvement. In this context, several mechanisms of action are likely to occur at the same time, consistently with the presence of different light absorbers within the skin. In our previous studies we observed the wound healing in superficial abrasions in an in vivo murine model. The results evidenced that both inflammatory infiltrate and myofibroblasts activity increase after irradiation. In this study we focused on evaluating the consequences of light absorption in fibroblasts from human cells culture: they play a key role in wound healing, both in physiological conditions and in pathological ones, such as keloid scarring. In particular we used keloids fibroblasts as a new target in order to investigate a possible metabolic or cellular mechanism correlation. Human keloid tissues were excised during standard surgery and immediately underwent primary cell culture extraction. Fibroblasts were allowed to grow in the appropriate conditions and then exposed to blue light. A metabolic colorimetric test (WST-8) was then performed. The tests evidenced an effect in mitochondrial activity, which could be modulated by the duration of the treatment. Electrophysiology pointed out a different behavior of irradiated fibroblasts. In conclusion, the Blue LED light affects the metabolic activity of fibroblasts and thus the cellular proliferation rate. No specific effect was found on keloid fibroblasts, thus indicating a very basic intracellular component, such as cytochromes, being the target of the treatment.

Vibration Anesthesia for Pain Reduction During Intralesional Steroid Injection for Keloid Treatment.

PubMed

Park, Kui Young; Lee, Yohan; Hong, Ji Yeon; Chung, Won Soon; Kim, Myeung Nam; Kim, Beom Joon

2017-05-01

Patients suffer significant pain during intralesional steroid injection treatment for keloids and hypertrophic scars. Vibration anesthesia has been shown to effectively and safely alleviate pain sensations, likely by reducing pain transmission from peripheral receptors to the brain. The objective was to evaluate the efficacy, safety, and patient satisfaction associated with vibration anesthesia for reducing pain during intralesional corticosteroid injection. The authors recruited 40 patients with 58 keloids who were scheduled to undergo intralesional triamcinolone acetonide (TA) injections. Half of each keloid was injected with concomitant vibration anesthesia, whereas the other half was injected without vibration anesthesia. Pain experienced by patients during both procedures was assessed according to visual analog scale (VAS) score. The authors also assessed procedure safety. The mean VAS score during intralesional TA injection therapy without vibration was 5.88 ± 2.34. By contrast, the same patients yielded a mean VAS score during intralesional TA injection therapy with vibration of 3.28 ± 1.85; the difference between the mean scores was significant (p < .05). Thirty-nine (97.5%) patients tolerated this therapy well. Vibration anesthesia is a promising option for reducing pain during keloid treatment with intralesional steroid injection.

Psychological stress as a risk factor for postoperative keloid recurrence.

PubMed

Furtado, Fabianne; Hochman, Bernardo; Farber, Paulo Luiz; Muller, Marisa Campio; Hayashi, Lilian Fukusima; Ferreira, Lydia Masako

2012-04-01

To investigate psychological stress on the prognosis of the postoperative recurrence of keloids. Patients with keloids (n=25), candidates for surgical resection and postoperative radiotherapy, had their psychological stress evaluated on the day before the surgical procedure. The parameters evaluated were pain and itching (Visual Numerical Scale), quality of life (Questionnaire QualiFibro/Cirurgia Plástica-UNIFESP), perceived stress (Perceived Stress Scale), depression and anxiety (Hospital Depression and Anxiety Scale), salivary cortisol and minimum and maximum galvanic skin responses (GSR) at rest and under stress (i.e., while the questionnaires were being filled out). Patients were evaluated during the 3rd, 6th, 9th and 12th months of postoperative care. During each return visit, two experts classified the lesions as non-recurrent and recurrent. The recurrence group presented the greatest values in GSR during a stressful situation. The chance of recurrence increased by 34% at each increase of 1000 arbitrary units in maximum GSR during stress. Psychological stress influenced the recurrence of keloids. Copyright © 2012 Elsevier Inc. All rights reserved.

A new treatment of hypertrophic and keloid scars with combined triamcinolone and verapamil: a retrospective study.

PubMed

Kant, S B; van den Kerckhove, E; Colla, C; Tuinder, S; van der Hulst, R R W J; Piatkowski de Grzymala, A A

2018-01-01

Since the management of keloid and hypertrophic scars still remains a difficult clinical problem, there is need for adequate, effective therapy. In this study, we explored for the first time the efficacy and the potential synergetic effect of combined triamcinolone and verapamil for the treatment of hypertrophic and keloid scars. The objective was to assess the efficacy of combined intralesional triamcinolone and verapamil therapy for hypertrophic and keloid scars. Fifty-eight patients with hypertrophic scars ( n  = 31) and keloid scars ( n  = 27) were included. A specific injection therapy scheme was applied. Five follow-up moments were chosen, with a maximum follow-up of nearly 2 years. The effects of combination therapy on scar pliability, thickness, relief, vascularization, surface area, pain, and pruritus were examined by means of the Patient and Observer Scar Assessment Scale (POSAS). Our results reveal a fast and abiding improvement of both keloid and hypertrophic scars after treatment with the combination therapy. All POSAS components showed a reduction in scar score, while scar relief, pain, itchiness, and surface area improved significantly ( P  < 0.05) in keloids. Significant improvement in hypertrophic scars was found in scar pigmentation, vascularization, pliability, thickness, pain, and surface area. Overall POSAS scores revealed statistically significant decreases between baseline and 3-4 months, 4-6 months, and >12 months after start of therapy in both keloids and hypertrophic scars. This study reveals that combined therapy of triamcinolone and verapamil results in overall significant scar improvement with a long-term stable result.Level of evidence: Level IV, therapeutic study.

Techniques for Optimizing Surgical Scars, Part 2: Hypertrophic Scars and Keloids.

PubMed

Potter, Kathryn; Konda, Sailesh; Ren, Vicky Zhen; Wang, Apphia Lihan; Srinivasan, Aditya; Chilukuri, Suneel

2017-01-01

Surgical management of benign or malignant cutaneous tumors may result in noticeable scars that are of great concern to patients, regardless of sex, age, or ethnicity. Techniques to optimize surgical scars are discussed in this three-part review. Part 2 focuses on scar revision for hypertrophic and keloids scars. Scar revision options for hypertrophic and keloid scars include corticosteroids, bleomycin, fluorouracil, verapamil, avotermin, hydrogel scaffold, nonablative fractional lasers, ablative and fractional ablative lasers, pulsed dye laser (PDL), flurandrenolide tape, imiquimod, onion extract, silicone, and scar massage.

Low-Level Light Therapy with 410 nm Light Emitting Diode Suppresses Collagen Synthesis in Human Keloid Fibroblasts: An In Vitro Study.

PubMed

Lee, Hyun Soo; Jung, Soo-Eun; Kim, Sue Kyung; Kim, You-Sun; Sohn, Seonghyang; Kim, You Chan

2017-04-01

Keloids are characterized by excessive collagen deposition in the dermis, in which transforming growth factor β (TGF-β)/Smad signaling plays an important role. Low-level light therapy (LLLT) is reported as effective in preventing keloids in clinical reports, recently. To date, studies investigating the effect of LLLT on keloid fibroblasts are extremely rare. We investigated the effect of LLLT with blue (410 nm), red (630 nm), and infrared (830 nm) light on the collagen synthesis in keloid fibroblasts. Keloid fibroblasts were isolated from keloid-revision surgery samples and irradiated using 410-, 630-, 830-nm light emitting diode twice, with a 24-hour interval at 10 J/cm 2 . After irradiation, cells were incubated for 24 and 48 hours and real-time quantitative reverse transcription polymerase chain reaction was performed. Western blot analysis was also performed in 48 hours after last irradiation. The genes and proteins of collagen type I, TGF-β1, Smad3, and Smad7 were analyzed. We observed no statistically significant change in the viability of keloid fibroblasts after irradiation. Collagen type I was the only gene whose expression significantly decreased after irradiation at 410 nm when compared to the non-irradiated control. Western blot analysis showed that LLLT at 410 nm lowered the protein levels of collagen type I compared to the control. LLLT at 410 nm decreased the expression of collagen type I in keloid fibroblasts and might be effective in preventing keloid formation in their initial stage.

Bilateral breast keloids in an elderly woman associated with bilateral breast cancers and high concentration of serum tumor growth factor-β.

PubMed

Sakaguchi, Masanobu; Fukumoto, Takeshi; Fujishima, Fumiyoshi; Fukuda, Kaori; Kozaru, Takeshi; Ban, Masao; Oka, Masahiro

2017-11-01

We report a case of bilateral annular breast keloids in a 72-year-old woman who had been suffering from bilateral breast cancers. Histopathologically, the keloids showed unique distribution of α-SMA+, CD34- myofibroblasts and α-SMA-, CD34+ fibroblasts depending on the region. High serum levels of tumor growth factor-β were detected at 6 months after the development of the breast keloids, but not at 10 months. CD163-positive cells were abundantly detected in the skin of the elevated portion of the keloids. In contrast, these cells were considerably less numerous in the skin of the central healing portion compared with the skin of the elevated expanding portion. One interesting idea based on these results is that high levels of tumor growth factor-β released from CD163-positive cells played a crucial role in the formation of breast keloids through active induction of fibroblast differentiation into myofibroblasts. The present case strongly supports the previously proposed idea that keloids can form as a paraneoplastic phenomenon in breast cancer patients with keloid constitution. © 2017 Japanese Dermatological Association.

A Radiobiological Analysis of Multicenter Data for Postoperative Keloid Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flickinger, John C., E-mail: flickingerjc@upmc.ed

2011-03-15

Purpose: To identify factors significantly affecting recurrence rates after postoperative external beam radiotherapy (XRT) of keloids, and to delineate any radiation dose response and effects of radiation dose per fraction. Methods and Materials: A comprehensive literature review was performed to compile a database of 2,515 resected keloids (36.9% earlobe). Postoperative XRT was 45- to 100-kV X-rays in 27.0% or 120- to 250-kV X-rays in 11.1%, Co-60 in 1.9%, Sr-90 in 4.7%, 1.5- to 9-MeV electrons in 26.5%, and no XRT in 28.8%. In the 1,791 irradiated patients, the median radiation parameters were as follows: total dose, 15 Gy (range, 6-30more » Gy); dose per fraction, 5.0 Gy (range, 2-15 Gy); fractions, 3 (range, 1-10); and time, 7 days (range, 0-33 days). Results: Multivariate stepwise logistic regression correlated decreased keloid recurrence with earlobe location (p = 1.98E-10; odds ratio, 0.34), biologically effective dose (p = 1.01E-27), and treatment with electron beam or Co-60 vs. other techniques (p = 0.0014; odds ratio, 0.72). Different radiobiological models calculated values of {alpha}/{beta} = 1.12 to 2.86 (mean, 2.08) and time (repopulation) correction factors for biologically effective dose from 0.98 to 2.13 Gy per day (mean, 1.34) starting 10 days after surgery. Different models (with {alpha}/{beta} = 2.08) predicted that doses needed for 90% and 95% control with 3 fractions of postoperative electron beam were 16.0 to 16.2 Gy and 18.3 to 19.2 Gy, respectively, in less than 10 days for earlobe keloids and 21.5 to 22.2 Gy and 23.4 to 24.8 Gy, respectively, in less than 10 days for other sites. Conclusions: Postoperative keloid radiotherapy requires moderately high doses and optimal technique to be effective. The relatively low {alpha}/{beta} ratio indicates that radiotherapy with a limited number of fractions and high doses per fraction is the best strategy.« less

The Effects of Postoperative Intralesional Corticosteroids in the Prevention of Recurrent Earlobe Keloids: A Multispecialty Retrospective Review.

PubMed

Gold, Daniel A; Sheinin, Renee; Jacobsen, Gordon; Jones, Lamont R; Ozog, David M

2018-06-01

Effective treatment of keloids is challenging because the recurrence rate after surgical excision is high. Data on the best treatment practices are lacking. To investigate the recurrence rate after surgical excision of earlobe keloids based on a postoperative intralesional corticosteroid injection protocol. Retrospective chart review was performed from January 1, 2005, to March 31, 2016, of patients who had excision of ear keloids within the departments of dermatology, otorhinolaryngology, and plastic surgery. The number of postoperative injections was recorded, recurrence was reported by the patient, and the efficacy of an injection protocol was evaluated. There were 277 charts reviewed. Appropriate data were available for 184 patients. A statistically significant difference was found with recurrence associated with a lower number of injections (p < .001). Keloids were more likely to recur if they were not treated with a planned serial injection protocol (p < .001) or if they were treated outside the department of dermatology (p < .001). Intralesional corticosteroid injection after surgical excision of earlobe keloids statistically minimizes the risk of recurrence.

Application of topical mitomycin C to the base of shave-removed keloid scars to prevent their recurrence.

PubMed

Bailey, J N R; Waite, A E; Clayton, W J; Rustin, M H A

2007-04-01

Keloid scars are formed by over-activity of fibroblasts producing collagen and they cause significant morbidity both from their appearance and from their symptoms. Existing treatments are often unsatisfactory. Topical mitomycin C is known to inhibit fibroblast proliferation. To determine whether application of mitomycin C to the base of shave-removed keloids would prevent their recurrence. Ten patients had all or part of their keloid shave-removed. After haemostasis topical mitomycin C 1 mg mL(-1) was applied for 3 min. This application was repeated after 3 weeks. The keloids were photographed before treatment and the patients were reviewed every 2 months for a total of 6 months when a final photograph of the keloid site was taken. The patients and the Clinical Trials Unit staff scored the outcome on a linear analogue scale of 0-10, where 0 = disappointed and 10 = delighted. The pretreatment and 6-month post-treatment photographs were also assessed by two dermatologists who were not involved in the clinical trial. Four of the 10 patients were delighted with the outcome of treatment and only one was disappointed. On average there was an 80% satisfied outcome. This new treatment of keloids has been shown to be effective in the majority of patients but further studies are required to confirm this benefit.

Upregulation of autophagy and glycolysis markers in keloid hypoxic-zone fibroblasts: Morphological characteristics and implications.

PubMed

Ryoko, Okuno; Ito, Yuko; Eid, Nabil; Otsuki, Yoshinori; Kondo, Yoichi; Ueda, Koichi

2018-05-29

Keloid is a fibro-proliferative skin disorder with tumor-like behavior and dependence on anaerobic glycolysis (the Warburg effect), but its exact pathogenesis is unknown. Although autophagy is widely accepted as a lysosomal pathway for cell survival and cellular homeostasis (specifically upon exposure to stressors such as hypoxia), very few studies have investigated the involvement of autophagy and related glycolytic effectors in keloidogenesis. Here the authors examined the expression and cellular localization of autophagy proteins (LC3, pan-cathepsin), glycolytic markers (LDH, MCT1, MCT4) and the transcription factor HIF isoforms in human keloid samples using immunohistochemical analysis and double-labeling immunofluorescence methods. Based on H&E staining and expression of CD31, keloids were compartmentalized into hypoxic central and normoxic marginal zones. Vimentin-expressing fibroblasts in the central zone exhibited greater autophagy than their marginal-zone counterparts, as evidenced by increased LC3 puncta formation and co-localization with lysosomal pan-cathepsin. LDH (a lactate stimulator), MCT4 (a lactate exporter) and HIF-1 α expression levels were also higher in central-zone fibroblasts. Conversely, HIF-2 α expression was upregulated in fibroblasts and endothelial cells of the peripheral zone, while MCT1 was expressed in both zones. Taken together, these observations suggest that upregulation of autophagy and glycolysis markers in keloid hypoxic-zone fibroblasts may indicate a prosurvival mechanism allowing the extrusion of lactate to marginal-zone fibroblasts via metabolic coupling. The authors believe this is the first report on differential expression of autophagic and glycolytic markers in keloid-zone fibroblasts. The study results indicate that autophagy inhibitors and MCT4 blockers may have therapeutic implications in keloid treatment.

Low-Level Light Therapy with 410 nm Light Emitting Diode Suppresses Collagen Synthesis in Human Keloid Fibroblasts: An In Vitro Study

PubMed Central

Lee, Hyun Soo; Jung, Soo-Eun; Kim, Sue Kyung; Kim, You-Sun; Sohn, Seonghyang

2017-01-01

Background Keloids are characterized by excessive collagen deposition in the dermis, in which transforming growth factor β (TGF-β)/Smad signaling plays an important role. Low-level light therapy (LLLT) is reported as effective in preventing keloids in clinical reports, recently. To date, studies investigating the effect of LLLT on keloid fibroblasts are extremely rare. Objective We investigated the effect of LLLT with blue (410 nm), red (630 nm), and infrared (830 nm) light on the collagen synthesis in keloid fibroblasts. Methods Keloid fibroblasts were isolated from keloid-revision surgery samples and irradiated using 410-, 630-, 830-nm light emitting diode twice, with a 24-hour interval at 10 J/cm2. After irradiation, cells were incubated for 24 and 48 hours and real-time quantitative reverse transcription polymerase chain reaction was performed. Western blot analysis was also performed in 48 hours after last irradiation. The genes and proteins of collagen type I, TGF-β1, Smad3, and Smad7 were analyzed. Results We observed no statistically significant change in the viability of keloid fibroblasts after irradiation. Collagen type I was the only gene whose expression significantly decreased after irradiation at 410 nm when compared to the non-irradiated control. Western blot analysis showed that LLLT at 410 nm lowered the protein levels of collagen type I compared to the control. Conclusion LLLT at 410 nm decreased the expression of collagen type I in keloid fibroblasts and might be effective in preventing keloid formation in their initial stage. PMID:28392641

Surgical excision and immediate postoperative radiotherapy versus cryotherapy and intralesional steroids in the management of keloids: a prospective clinical trial.

PubMed

Emad, Maryam; Omidvari, Shapour; Dastgheib, Ladan; Mortazavi, Afshin; Ghaem, Haleh

2010-01-01

To compare the efficacy and tolerability of surgical excision and radiotherapy with those of cryotherapy and intralesional steroid treatment of keloids. Twenty-six patients with a total of 76 keloids were enrolled in this study. Nineteen patients with 44 keloids underwent surgical excision combined with immediate 12-Gy irradiation (group A) while the remaining 9 patients with 32 keloids received multiple sessions of intralesional steroid treatment after cryotherapy which continued until flattening of lesion(s) occurred (group B). Two patients were included in both treatment groups. All patients were followed up at regular intervals for at least 1 year. In both treatment groups, keloids responded well without any major side effect. While patients of group A were all satisfied, those of group B (with a mean number of treatment sessions of 5.84 +/- 2.51) experienced more side effects, a more prolonged course, a higher recurrence rate and less satisfaction. This study showed that surgery plus immediate postoperative irradiation was an effective and relatively safe choice for treatment of keloids. Although cryotherapy combined with intralesional steroids was associated with more side effects and higher relapse rates, it could be a good choice for small and newly formed keloids. Copyright 2010 S. Karger AG, Basel.

Intralesional cryotherapy for hypertrophic scars and keloids: a review

PubMed Central

O’Boyle, Ciaran P; Shayan-Arani, Holleh; Hamada, Maha Wagdy

2017-01-01

Introduction: Hypertrophic and keloid scarring remain notoriously troublesome for patients to tolerate and frustratingly difficult for clinicians to treat. Many different treatment modalities exist, signifying the failure of any method to achieve consistently excellent results. Intralesional cryotherapy is a relatively recent development that uses a double lumen needle, placed through the core of a keloid or hypertrophic scar, to deliver nitrogen vapour, which freezes the scar from its core, outwards. Methods: This article provides a comprehensive review of the literature on intralesional cryotherapy for hypertrophic scars and keloids. A systematic review or meta-analysis was not possible, since the existing articles did not permit this. Results: A search of English language, peer-reviewed literature was carried out. The evidence base was found to be low (level 4). In addition, much of the published evidence comes from a very few groups. Despite this, consistent findings from case series suggest that the technique is safe and achieves good scar reduction with very few treatments. Adverse effects include depigmentation, recurrence and pain. Pain and recurrence appear to be uncommon and depigmentation may be temporary. Discussion: Well-constructed, prospectively recruited comparative trials are absent from the literature. These are strongly encouraged, in order to strengthen general confidence in this technique and in the repeatability of outcomes reported thus far. PMID:29799581

Comparative effect and safety of verapamil in keloid and hypertrophic scar treatment: a meta-analysis.

PubMed

Li, Zhouna; Jin, Zhehu

2016-01-01

Keloids and hypertrophic scars are the most common types of pathological scarring. Traditionally, keloids have been considered as a result of aberrant wound healing, involving excessive fibroblast participation that is characterized by hyalinized collagen bundles. However, the usefulness of this characterization has been questioned. In recent years, studies have reported the appropriate use of verapamil for keloids and hypertrophic scars. Searches were conducted on the databases Medline, Embase, Cochrane, PubMed, and China National Knowledge Infrastructure from 2006 to July 2016. State12.0 was used for literature review, data extraction, and meta-analysis. Treatment groups were divided into verapamil and nonverapamil group. Nonverapamil group includes steroids and intense pulsed light (IPL) therapy. Total effective rates include cure rate and effective rate. Cure: skin lesions were completely flattened, became soft and symptoms disappeared. Efficacy: skin lesions subsided, patient significantly reduced symptoms. Inefficient definition of skin was progression free or became worse. Random-effects model was used for the meta-analysis. Six studies that included 331 patients with keloids and hypertrophic scars were analyzed. Analysis of the total effective rate of skin healing was performed. The total effective rates in the two groups were 54.07% (verapamil) and 53.18% (nonverapamil), respectively. The meta-analysis showed that there was no difference between the two groups. We also compared the adverse reactions between the verapamil treatment group and the steroids treatment group in two studies, and the result indicated that the verapamil group showed less adverse reactions. There were no differences between the application of verapamil and nonverapamil group in keloids and hypertrophic scars treatment. Verapamil could act as an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars. A larger number of studies are required to

Comparative effect and safety of verapamil in keloid and hypertrophic scar treatment: a meta-analysis

PubMed Central

Li, Zhouna; Jin, Zhehu

2016-01-01

Background Keloids and hypertrophic scars are the most common types of pathological scarring. Traditionally, keloids have been considered as a result of aberrant wound healing, involving excessive fibroblast participation that is characterized by hyalinized collagen bundles. However, the usefulness of this characterization has been questioned. In recent years, studies have reported the appropriate use of verapamil for keloids and hypertrophic scars. Methods Searches were conducted on the databases Medline, Embase, Cochrane, PubMed, and China National Knowledge Infrastructure from 2006 to July 2016. State12.0 was used for literature review, data extraction, and meta-analysis. Treatment groups were divided into verapamil and nonverapamil group. Nonverapamil group includes steroids and intense pulsed light (IPL) therapy. Total effective rates include cure rate and effective rate. Cure: skin lesions were completely flattened, became soft and symptoms disappeared. Efficacy: skin lesions subsided, patient significantly reduced symptoms. Inefficient definition of skin was progression free or became worse. Random-effects model was used for the meta-analysis. Results Six studies that included 331 patients with keloids and hypertrophic scars were analyzed. Analysis of the total effective rate of skin healing was performed. The total effective rates in the two groups were 54.07% (verapamil) and 53.18% (nonverapamil), respectively. The meta-analysis showed that there was no difference between the two groups. We also compared the adverse reactions between the verapamil treatment group and the steroids treatment group in two studies, and the result indicated that the verapamil group showed less adverse reactions. Conclusion There were no differences between the application of verapamil and nonverapamil group in keloids and hypertrophic scars treatment. Verapamil could act as an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars. A

Ear-lobe keloids: treatment by a protocol of surgical excision and immediate postoperative adjuvant radiotherapy.

PubMed

Ragoowansi, R; Cornes, P G; Glees, J P; Powell, B W; Moss, A L

2001-09-01

There is no universally agreed policy for treating keloid scars of the ear lobe following piercing. We treated 35 patients (34 women) for high-risk ear-lobe keloids; the average age was 24 years (range: 16-44 years). All had failed to respond to prior treatment with massage and silicone, and corticosteroid injection. The keloids were excised extralesionally and the defects were closed with interrupted prolene sutures. The operative scar was covered with topical 2% lignocaine-0.25% chlorhexidine sterile lubricant gel under a transparent adhesive dressing. Adjuvant postoperative radiotherapy of 10 Gy, applied as 100 kV photons (4 mm high-voltage therapy (HVT) Al), was given within 24 h of surgery. All keloid scars were controlled at 4 weeks' follow-up. At 1 year, three out of 34 cases followed up had relapsed (probability of control: 91.2%). At 5 years, a further four out of the remaining 31 patients had relapsed (cumulative probability of control at 5 years: 79.4%). There were no cases of serious toxicity. Copyright 2001 The British Association of Plastic Surgeons.

Perioperative Interstitial High-Dose-Rate Brachytherapy for the Treatment of Recurrent Keloids: Feasibility and Early Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Ping, E-mail: ping.jiang@uksh.de; Baumann, René; Dunst, Juergen

Purpose: To prospectively evaluate high-dose-rate brachytherapy in the treatment of therapy-resistant keloids and report first results, with emphasis on feasibility and early treatment outcome. Methods and Materials: From 2009 to 2014, 24 patients with 32 recurrent keloids were treated with immediate perioperative high-dose-rate brachytherapy; 3 patients had been previously treated with adjuvant external beam radiation therapy and presented with recurrences in the pretreated areas. Two or more different treatment modalities had been tried in all patients and had failed to achieve remission. After (re-)excision of the keloids, a single brachytherapy tube was placed subcutaneously before closing the wound. The target volumemore » covered the scar in total length. Brachytherapy was given in 3 fractions with a single dose of 6 Gy in 5 mm tissue depth. The first fraction was given within 6 hours after surgery, the other 2 fractions on the first postoperative day. Thus, a total dose of 18 Gy in 3 fractions was administered within 36 hours after the resection. Results: The treatment was feasible in all patients. No procedure-related complications (eg, secondary infections) occurred. Nineteen patients had keloid-related symptoms before treatment like pain and pruritus; disappearance of symptoms was noticed in all patients after treatment. After a median follow-up of 29.4 months (range, 7.9-72.4 months), 2 keloid recurrences and 2 mildly hypertrophied scars were observed. The local control rate was 94%. Pigmentary abnormalities were detected in 3 patients, and an additional 6 patients had a mild delay in the wound-healing process. Conclusions: The early results of this study prove the feasibility and the efficacy of brachytherapy for the prevention of keloids. The results also suggest that brachytherapy may be advantageous in the management of high-risk keloids or as salvage treatment for failure after external beam therapy.« less

Experience of silicone gel sheets for patients with keloid scars after median sternotomy.

PubMed

Sakuraba, Motoki; Takahashi, Nobumasa; Akahoshi, Taku; Miyasaka, Yoshikazu; Suzuki, Kenji

2010-09-01

It is often difficult to control hypertrophic scars and keloids with drug therapy, steroid injection, surgery, radiation therapy, laser, or wound pressing. Use of silicone gel to treat hypertrophic burn scars and fresh incisions has yielded encouraging results. We report our experience of silicone gel sheets for patients with keloids following median sternotomy. Nine patients underwent a median sternotomy and received other therapies before participating in this treatment. A silicone gel sheet was placed directly on the keloid scar and maintained at all times. Sheets were replaced every 4 weeks for a total treatment duration of 24 weeks. The scar area was measured, and subjective symptoms were determined prior to therapy and after completion of therapy. There were three men and six women, with a mean age of 45.2 years (range 22-69 years). Progression of protuberance and rub was seen in one patient. Scar redness and cramping were either diminished or unchanged in all patients. Itching progressed in two patients. After 6 months, the area of the scar relative to its initial area was 0.98 (range 0.78-1.27). Harmful events did not occur. A silicone gel sheet is effective for treating keloid scars following median sternotomy. Silicone gel sheets are safe and easy to use and do not aggravate any subjective symptoms.

[Umbilical endometriosis mimicking a keloid in a young black woman: A case report].

PubMed

Kourouma, H-S; Ecra, E-J; Allou, A-S; Kouyaté, M; Kouassi, Y-I; Kaloga, M; Kouassi, K-A; Kassi, K; Kouamé, K; Ahogo, C; Gbery, I-P; Sangaré, A

2017-10-01

Most umbilical tumors are diagnosed as benign tumors, umbilical metastases of abdominal and pelvic tumors, or Sister Marie Joseph nodule. Herein, we report a case of cutaneous umbilical endometriosis mistaken for a keloid. A young black woman aged 26 consulted for a painful umbilical tumefaction. She had noted the appearance of a nodule of the umbilicus 10 months ago with bleeding during her menstrual periods. Skin examination revealed a firm and painful umbilical nodule 2.5cm in diameter. She was treated with corticosteroid injections for one month for umbilical keloid. Given that the symptoms recurred regularly at the time of menstruation, we suspected umbilical endometriosis. This diagnosis was finally confirmed by histopathological examination and hormone therapy was instituted on gynecological advice before scheduled surgical excision. In a setting of an umbilical tumor simulating a keloid associated with cyclical symptoms in a black woman, the diagnosis of umbilical endometriosis should not be overlooked by the dermatologist. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The influence of genistein on free radicals in normal dermal fibroblasts and keloid fibroblasts examined by EPR spectroscopy.

PubMed

Jurzak, Magdalena; Ramos, Paweł; Pilawa, Barbara

2017-01-01

Normal and keloid fibroblasts were examined using X-band (9.3 GHz) electron paramagnetic resonance spectroscopy. The effect of genistein on the concentration of free radicals in both normal dermal and keloid fibroblasts after ultraviolet irradiation was investigated. The highest concentration of free radicals was seen in keloid fibroblasts, with normal fibroblasts containing a lower concentration. The concentration of free radicals in both normal and keloid fibroblasts was altered in a concentration-dependent manner by the presence of genistein. The change in intra-cellular free radical concentration after the ultraviolet irradiation of both normal and keloid fibroblasts is also discussed. The antioxidant properties of genistein, using its 1,1-Diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging activity as a model, were tested, and the effect of ultraviolet irradiation on its interaction with free radicals was examined. The electron paramagnetic resonance spectra of DPPH showed quenching by genistein. The interaction of genistein with DPPH free radicals in the absence of ultraviolet irradiation was shown to be slow, but this interaction was much faster under ultraviolet irradiation. Ultraviolet irradiation enhanced the free radical-scavenging activity of genistein.

Chest wall abscesses due to continuous application of silicone gel sheets for keloid management

PubMed Central

Tang, Hon-Lok; Lau, Keith K; Sam, Ramin; Ing, Todd S

2015-01-01

A patient with three episodes of chest wall abscesses as a result of 6 years of round-the-clock, uninterrupted (except during bathing) application of silicone gel sheets to a chest wall keloid is described. Two of the episodes occurred during hot weather. It is suggested that, in the space beneath the silicone sheet, the higher humidity and temperature, both generated as a result of prolonged sheeting, especially during hot weather, might have caused the keloid and its neighbouring skin to become soggy. This sogginess might have facilitated bacterial invasion. It is suggested that some sheeting-free time during a 24 h period might be indicated so that a keloid and its adjacent skin have the time to recover from their sheeting-induced sogginess. A sheeting-free period might especially be needed in the face of sweat accumulation beneath the silicone sheet. PMID:25920733

Chest wall abscesses due to continuous application of silicone gel sheets for keloid management.

PubMed

Tang, Hon-Lok; Lau, Keith K; Sam, Ramin; Ing, Todd S

2015-04-28

A patient with three episodes of chest wall abscesses as a result of 6 years of round-the-clock, uninterrupted (except during bathing) application of silicone gel sheets to a chest wall keloid is described. Two of the episodes occurred during hot weather. It is suggested that, in the space beneath the silicone sheet, the higher humidity and temperature, both generated as a result of prolonged sheeting, especially during hot weather, might have caused the keloid and its neighbouring skin to become soggy. This sogginess might have facilitated bacterial invasion. It is suggested that some sheeting-free time during a 24 h period might be indicated so that a keloid and its adjacent skin have the time to recover from their sheeting-induced sogginess. A sheeting-free period might especially be needed in the face of sweat accumulation beneath the silicone sheet. 2015 BMJ Publishing Group Ltd.

Variations in gap junctional intercellular communication and connexin expression in fibroblasts derived from keloid and hypertrophic scars.

PubMed

Lu, Feng; Gao, JianHua; Ogawa, Rei; Hyakusoku, Hiko

2007-03-01

Expression of connexins and other constituent proteins of gap junctions along with gap junctional intercellular communication are involved in cellular development and differentiation processes. In addition, an increasing number of hereditary skin disorders appear to be linked to connexins. Therefore, in this report, the authors studied in vitro gap junctional intercellular communication function and connexin expression in fibroblasts derived from keloid and hypertrophic scar patients. Fibroblasts harvested from each of six keloid and hypertrophic scar patients were used for this study. Gap junctional intercellular communication function was investigated using the gap fluorescence recovery after photobleaching method, and expression of connexin proteins was studied using quantitative confocal microscopic analyses. Compared with normal skin, a decreased level of gap junctional intercellular communication was seen in fibroblasts derived from hypertrophic scar tissue, whereas an extremely low gap junctional intercellular communication level was detected in fibroblasts derived from keloid tissue. We also detected little connexin 43 (Cx43) protein localized in fibroblasts derived from keloids. Moreover, Cx43 protein levels were much lower in fibroblasts derived from hypertrophic scars than in those derived from normal skin. The authors' data suggest that the loss of gap junctional intercellular communication and connexin expression may affect intercellular recognition and thus break the proliferation and apoptosis balance in fibroblasts derived from keloid and hypertrophic scar tissue.

Topical Silicone Sheet Application in the Treatment of Hypertrophic Scars and Keloids.

PubMed

Westra, Iris; Pham, Hth; Niessen, Frank B

2016-10-01

Objective: Since the early 1980s, topical silicone sheets have been used in the treatment of hypertrophic scars and keloids.This study aimed to determine the optimal duration and application of these sheets. Design: multi-centered therapeutic study. Setting and participants: A total of 224 patients were included in this study; 205 patients with hypertrophic scars and 19 patients with keloids. Patients received treatment with a topical silicone sheet. Treated scars varied in age, ranging from two weeks to 62 years and treatment time ranged from one month to 16 months. Assessment of the scars was performed by the use of standardized study forms and digital photography. Measurements: Skin therapists objectively assessed the scars on its color, thickness, and elasticity. Patients themselves subjectively assessed their perception of their scar and their experience with the usage of the topical silicone sheet. Results: After applying the topical silicone sheet, all scars, regardless of type of scar and maturity, improved significantly in color, thickness, and elasticity. Conclusion: In this study, treatment with the topical silicone sheet showed significant improvement on both hypertrophic scars and keloids. Best results were reached when the silicone sheet was applied at least four hours per day.

Ear keloids as a primary candidate for the application of mitomycin C after shave excision: in vivo and in vitro study.

PubMed

Chi, Seong Geun; Kim, Jun Young; Lee, Weon Ju; Lee, Seok-Jong; Kim, Do Won; Sohn, Mi Yeung; Kim, Gun Wook; Kim, Moon Bum; Kim, Byung Soo

2011-02-01

Although many methods have been developed to treat ear keloids, new therapeutic options are still needed. To determine the effects of topical mitomycin C (MC) on shave-removed wounds and fibroblasts of ear keloids. Fourteen ear keloids in 12 patients were shaved, and MC (1 mg/mL) was applied to the resected bed for 5 minutes. The application was repeated 3 weeks later. All patients were assessed 2, 4, and 6 months after the procedure to evaluate the cosmetic results, recurrence, and postsurgical complications. An in vitro study to determine the effects of MC on fibroblasts of the excised keloids was conducted using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the measurement of total cell counts, and immunoassay of DNA synthesis. Only one recurrence occurred (on the ear helix), and the patients were satisfied with the cosmetic outcomes. The results of the MTT assay, total cell counts, and DNA synthesis immunoassay confirmed the suppressive effects of MC on the keloid fibroblasts. The application of topical MC to the resected bed of shave-removed ear keloids was successful in preventing recurrences and providing an acceptable cosmetic outcome. © 2011 by the American Society for Dermatologic Surgery, Inc.

Asiaticoside hinders the invasive growth of keloid fibroblasts through inhibition of the GDF-9/MAPK/Smad pathway.

PubMed

Wu, Xin; Bian, Difei; Dou, Yannong; Gong, Zhunan; Tan, Qian; Xia, Yufeng; Dai, Yue

2017-08-01

Higher expression of growth differentiation factor-9 (GDF-9) in keloids compared with hypertrophic scars and normal skin tissues has been reported recently. The present study was performed to investigate the role of GDF-9 in keloid pathogenesis, and to elucidate its implication for asiaticoside in the keloid management. The data showed that GDF-9 could enhance the proliferation, migration, and invasion of keloid fibroblasts (KFs), while it only slightly elevated collagen expression, indicating that the effect of GDF-9 was opposite to that of TGF-β1. The bioactivity difference between GDF-9 and TGF-β1 could be explained by the different phosphorylated sites on the downstream Smad2/3. Moreover, asiaticoside could inhibit GDF-9-induced activation of MAPKs and Smad pathway in KFs. In conclusion, GDF-9 enhanced the invasive growth of KFs, which was achieved by phosphorylation of Smad 2/3 at the linker region through activation of MAPKs pathway. Asiaticoside hindered the invasive growth of KFs by inhibiting the GDF-9/MAPK/Smad pathway. © 2017 Wiley Periodicals, Inc.

A new argon gas-based device for the treatment of keloid scars with the use of intralesional cryotherapy.

PubMed

van Leeuwen, Michiel C E; Bulstra, Anne-Eva J; van Leeuwen, Paul A M; Niessen, Frank B

2014-12-01

Intralesional (IL) cryotherapy is a new promising technique for the treatment of keloid scars, in which the scar is frozen from inside. Multiple devices are available, mostly based on a simple liquid nitrogen Dewar system, which have a limited freezing capacity. Argon gas-based systems ensure accurate and highly controlled freezing and have shown to be effective within the field of oncologic surgery. However, this technique has never been used for the treatment of keloid scars. This prospective study evaluates an argon gas-based system for the treatment of keloids in a patient population including all Fitzpatrick skin types with a 1-year follow-up. Twenty-five patients with 30 keloid scars were included and treated with a device called Seednet (Galil Medical, Yokneam, Israel). Scar quality and possible scar recurrence were assessed before treatment and post treatment (6 and 12 months) with objective devices determining scar color, scar elasticity, scar volume, and patient's skin type. In addition, scars were evaluated using the Patient and Observer Scar Assessment Scale. After 12 months, a significant volume reduction of 62% was obtained, p = 0.05. Moreover, complaints of pain and itching were alleviated and scar quality had improved according to the Patient and Observer Scar Assessment Scale. Scar pigmentation recovered in 62% of all keloid scars within 12 months. Five out of 30 (17%) scars recurred within 12 months, three of which had previously been treated with liquid nitrogen-based IL cryotherapy. Both recurrent and persistent hypopigmentation were mainly seen in Afro-American patients. IL cryotherapy with the use of an argon gas-based system proves to be effective in the treatment of keloid scars, yielding volume reduction and low recurrence rates. Although hypopigmentation recovered in most cases, it is strongly related to non-Caucasian patients. Finally, additional treatment of keloid scars previously unresponsive to IL cryotherapy is predisposed to a high

Keloid in the gray reef shark, Carcharhinus amblyrhynchos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, A.C.; Hartley, F.K.

1976-04-01

A gray reef shark, Carcharhinus amblyrhynchos, was captured at Enewetak Atoll, the Marshall Islands, in 1972. Near the right pectoral fin was a large fungating tumor. Microscopically, no evidence of microorganisms or definite malignant transformation was observed, and inflammation and necrosis were minimal. However, the tumor appeared to be a keloid, the first to be reported in sharks.

Association of the plasminogen activator inhibitor-1 (PAI-1) Gene -675 4G/5G and -844 A/G promoter polymorphism with risk of keloid in a Chinese Han population.

PubMed

Wang, Yongjie; Long, Jianhong; Wang, Xiaoyan; Sun, Yang

2014-10-28

A keloid is pathological scar caused by aberrant response to skin injuries, characterized by excessive accumulation of histological extracellular matrix, and occurs in genetically susceptible individuals. Plasminogen activator inhibitor-1 (PAI-1) has been implicated in the pathogenesis of keloid. We investigated the association between PAI-1 polymorphisms and plasma PAI-1 level with keloid risk. A total of 242 Chinese keloid patients and 207 controls were enrolled in this study. Polymerase chain reaction-restriction technique was used to determine PAI-1 promoter polymorphism (-675 4G/5G and -844 A/G) distribution. Plasma PAI-1 levels were detected using enzyme-linked immunosorbent assay (ELISA). There was a statistically significant difference in the distribution of PAI-1 -675 4G/5G polymorphism between keloid patients and healthy controls. 4G/4G carriers were more likely to develop keloid. In contrast, the -844 A/G polymorphism distribution did not vary significantly between keloid patients and controls. The keloid patients group had a significantly higher plasma PAI-1 level than the control group. In the -675 4G/4G carrier population, the plasma PAI-1 levels were significant higher in keloid patients compared with controls. Our study provides evidence that PAI-1 promoter polymorphism -675 4G/5G and plasma PAI-1 level are associated with keloid risk. PAI-1 -675 4G/5G polymorphism may be an important hereditary factor responsible for keloid development in the Chinese Han population.

Successful Treatment of Keloid With Fractionated Carbon Dioxide (CO2) Laser and Laser-Assisted Drug Delivery of Triamcinolone Acetonide Ointment in an African-American Man.

PubMed

Kraeva, Ekaterina; Ho, Derek; Jagdeo, Jared

2017-09-01

Keloids are fibrous growths that occur as a result of abnormal response to dermal injury. Keloids are cosmetically disfiguring and may impair function, often resulting in decreased patient quality-of-life. Treatment of keloids remains challenging, and rate of recurrence is high. We present a case of a 39-year-old African-American man (Fitzpatrick VI) with a 10-year history of keloid, who was successfully treated with eight sessions of fractionated carbon dioxide (CO2) laser immediately followed by laser-assisted drug delivery (LADD) of topical triamcinolone acetonide (TAC) ointment and review the medical literature on fractionated CO2 laser treatment of keloids. To the best of our knowledge, this is the first report of successful treatment of a keloid using combination therapy of fractionated CO2 laser and LADD with topical TAC ointment in an African-American man (Fitzpatrick VI) with excellent cosmetic results sustained at 22 months post-treatment. We believe that this combination treatment modality may be safe and efficacious for keloids in skin of color (Fitzpatrick IV-VI) and other patients. This case highlights the ability of laser surgeons to safely use fractionated CO2 lasers in patients of all skin colors.

J Drugs Dermatol. 2017;16(9):925-927.

Association of the Plasminogen Activator Inhibitor-1 (PAI-1) Gene -675 4G/5G and -844 A/G Promoter Polymorphism with Risk of Keloid in a Chinese Han Population

PubMed Central

Wang, Yongjie; Long, Jianhong; Wang, Xiaoyan; Sun, Yang

2014-01-01

Background A keloid is pathological scar caused by aberrant response to skin injuries, characterized by excessive accumulation of histological extracellular matrix, and occurs in genetically susceptible individuals. Plasminogen activator inhibitor-1 (PAI-1) has been implicated in the pathogenesis of keloid. We investigated the association between PAI-1 polymorphisms and plasma PAI-1 level with keloid risk. Material/Methods A total of 242 Chinese keloid patients and 207 controls were enrolled in this study. Polymerase chain reaction-restriction technique was used to determine PAI-1 promoter polymorphism (-675 4G/5G and -844 A/G) distribution. Plasma PAI-1 levels were detected using enzyme-linked immunosorbent assay (ELISA). Results There was a statistically significant difference in the distribution of PAI-1 -675 4G/5G polymorphism between keloid patients and healthy controls. 4G/4G carriers were more likely to develop keloid. In contrast, the -844 A/G polymorphism distribution did not vary significantly between keloid patients and controls. The keloid patients group had a significantly higher plasma PAI-1 level than the control group. In the -675 4G/4G carrier population, the plasma PAI-1 levels were significant higher in keloid patients compared with controls. Conclusions Our study provides evidence that PAI-1 promoter polymorphism -675 4G/5G and plasma PAI-1 level are associated with keloid risk. PAI-1 -675 4G/5G polymorphism may be an important hereditary factor responsible for keloid development in the Chinese Han population. PMID:25350781

Tumor-Like Stem Cells Derived from Human Keloid Are Governed by the Inflammatory Niche Driven by IL-17/IL-6 Axis

PubMed Central

Zhang, Qunzhou; Yamaza, Takayoshi; Kelly, A. Paul; Shi, Shihong; Wang, Songlin; Brown, Jimmy; Wang, Lina; French, Samuel W.; Shi, Songtao; Le, Anh D.

2009-01-01

Background Alterations in the stem cell niche are likely to contribute to tumorigenesis; however, the concept of niche promoted benign tumor growth remains to be explored. Here we use keloid, an exuberant fibroproliferative dermal growth unique to human skin, as a model to characterize benign tumor-like stem cells and delineate the role of their “pathological” niche in the development of the benign tumor. Methods and Findings Subclonal assay, flow cytometric and multipotent differentiation analyses demonstrate that keloid contains a new population of stem cells, named keloid derived precursor cells (KPCs), which exhibit clonogenicity, self-renewal, distinct embryonic and mesenchymal stem cell surface markers, and multipotent differentiation. KPCs display elevated telomerase activity and an inherently upregulated proliferation capability as compared to their peripheral normal skin counterparts. A robust elevation of IL-6 and IL-17 expression in keloid is confirmed by cytokine array, western blot and ELISA analyses. The altered biological functions are tightly regulated by the inflammatory niche mediated by an autocrine/paracrine cytokine IL-17/IL-6 axis. Utilizing KPCs transplanted subcutaneously in immunocompromised mice we generate for the first time a human keloid-like tumor model that is driven by the in vivo inflammatory niche and allows testing of the anti-tumor therapeutic effect of antibodies targeting distinct niche components, specifically IL-6 and IL-17. Conclusions/Significance These findings support our hypothesis that the altered niche in keloids, predominantly inflammatory, contributes to the acquirement of a benign tumor-like stem cell phenotype of KPCs characterized by the uncontrolled self-renewal and increased proliferation, supporting the rationale for in vivo modification of the “pathological” stem cell niche as a novel therapy for keloid and other mesenchymal benign tumors. PMID:19907660

Adiponectin Is Involved in Connective Tissue Growth Factor-Induced Proliferation, Migration and Overproduction of the Extracellular Matrix in Keloid Fibroblasts.

PubMed

Luo, Limin; Li, Jun; Liu, Han; Jian, Xiaoqing; Zou, Qianlei; Zhao, Qing; Le, Qu; Chen, Hongdou; Gao, Xinghua; He, Chundi

2017-05-12

Adiponectin, an adipocyte-derived hormone, exerts pleiotropic biological effects on metabolism, inflammation, vascular homeostasis, apoptosis and immunity. Recently, adiponectin has been suggested to attenuate the progression of human dermal fibrosis. Connective tissue growth factor (CTGF) is induced in keloids and is thought to be participated in the formation of keloid fibrosis. However, the roles played by adiponectin in keloids remain unclear. In this study, we explored the effects of adiponectin on CTGF-induced cell proliferation, migration and the deposition of extracellular matrix (ECM) and their associated intracellular signalling pathways in keloid fibroblasts (KFs). We also explored possible mechanisms of keloid pathogenesis. Primary fibroblast cultures were established from foreskin biopsies and skin biopsies from patients with keloids. The expression of adiponectin and adiponectin receptors (adipoRs) was evaluated by reverse transcription-PCR (RT-PCR), quantitative real-time RT-PCR, immunofluorescence staining, and immunohistochemical analysis. Next, KFs and normal dermal fibroblasts (NFs) were treated with CTGF in the presence or absence of adiponectin. A cell counting kit-8 (CCK-8) and the Transwell assay were used to examine cell proliferation and migration. The level of the collagen I, fibronectin (FN) and α-smooth muscle actin (α-SMA) mRNAs and proteins were determined by quantitative real-time RT-PCR and western blotting. The effects of RNA interference (RNAi) targeting the adipoR genes were detected. Phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase-protein kinase (PI3K-Akt) were examined by western blotting to further investigate the signalling pathways. Furthermore, inhibitors of signal transduction pathways were investigated. The expression levels of adiponectin and adipoRs were significantly decreased in keloids compared with those

Bilateral congenital corneal keloids and anterior segment mesenchymal dysgenesis in a case of Rubinstein-Taybi syndrome.

PubMed

Rao, Srinivas K; Fan, Dorothy S P; Pang, C P; Li, Winnie W Y; Ng, Joan S K; Good, William V; Lam, Dennis S C

2002-01-01

To report the unusual association of bilateral corneal keloids and anterior segment mesenchymal dysgenesis in a child with Rubinstein-Taybi syndrome. Case report of a 2-year-old boy. Excision of the epicorneal mass in the right eye was followed by recurrence of the lesion. Multiple penetrating keratoplasties were unsuccessful in reconstructing the anterior segment because of recurrent corneal epithelial breakdown, suggesting limbal stem cell insufficiency. Histopathology and electron microscopy of the excised mass lesion showed features typical of a corneal keloid: thickened keratinized epithelium, absent Bowman's layer, and fibrovascular hyperplasia, with haphazard orientation of the collagen lamellae. Ultrasound biomicroscopy and intraoperative findings suggested a diagnosis of Peter anomaly, but genetic analysis did not show a PAX6 mutation. The findings in our patient add to the spectrum of ocular changes described in Rubinstein-Taybi syndrome and confirm earlier reports of poor ocular prognosis in corneal keloids and Rubinstein-Taybi syndrome.

Vaccine-associated fibrosarcoma with keloidal differentiation in a cat.

PubMed

Gumber, Sanjeev; Wakamatsu, Nobuko

2011-09-01

A 6-year-old Domestic Shorthair cat was presented with a history of subcutaneous mass of the lateral left hind limb. The subcutaneous mass developed over a period of approximately 16 months subsequent to administration of Feline leukemia virus vaccines. Based on the histopathological and immunohistochemical examination, the subcutaneous mass was diagnosed as vaccine-associated fibrosarcoma with keloidal differentiation.

Descriptive Study of Patients Receiving Excision and Radiotherapy for Keloids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Speranza, Giovanna; Sultanem, Khalil M.D.; Muanza, Thierry

Purpose: To review and describe our institution's outcomes in patients treated with external beam radiotherapy after keloid excision. Methods and Materials: This was a retrospective study. Patients who received radiotherapy between July 1994 and January 2004 after keloid excision were identified. A questionnaire was mailed regarding sociodemographic factors, early and late radiation toxicities, the need for additional therapy, and satisfaction level. All patients had received a total of 15 Gy in three daily 5-Gy fractions. Treatment started within 24 h after surgery and was delivered on a Siemens orthovoltage machine. The data were analyzed using the STATA statistical package. Results:more » A total of 234 patients were approached. The response rate was 41%, and 75% were female. The mean age was 36.5 years (range, 16-69 years). The patients were mainly of European (53.1%) or African (19.8%) descent. For early toxicity outcomes, 54.2% reported skin redness and 24% reported skin peeling. For late toxicity outcomes, 27% reported telangiectasia and 62% reported permanent skin color changes. No association was found with gender, skin color, or age for the late toxicity outcomes. Of the patients responding, 14.6% required adjuvant treatment. On a visual scale of 1-10 for the satisfaction level, 60% reported a satisfaction level of {>=}8. Telangiectasia was the most significant predictor of a low satisfaction level ({<=}3, p < 0.005). Conclusion: The results of our study have shown that orthovoltage-based radiotherapy after surgical excision for keloids is a good method for the prevention of relapse. It is well tolerated, causes little toxicity, and leads to a high patient satisfaction level.« less

Could −79 °C Spray-Type Cryotherapy Be an Effective Monotherapy for the Treatment of Keloid?

PubMed Central

Park, Tae Hwan; Cho, Hyeon-Ju; Lee, Jang Won; Kim, Chan Woo; Chong, Yosep; Chang, Choong Hyun; Park, Kyung-Soon

2017-01-01

Cryotherapy has been regarded as an effective modality for the treatment of keloids, and the spray-type device is one of the novel cryotherapeutic units. However, the biological mechanisms and therapeutic effects of this technique are incompletely studied. We evaluated the clinical efficacy of our cryotherapy protocol with molecular and pathologic evidence for the treatment of keloids. We evenly split each of ten keloid lesions into a non-treated (C−) and treated (C+) area; the C+ area was subjected to two freeze-thaw cycles of spray-type cryotherapy using −79 °C spray-type CryoPen™. This treatment was repeated after an interval of two weeks. The proliferation and migration abilities of the fibroblasts isolated from the dermis under the cryotherapy-treated or untreated keloid tissues (at least 5 mm deep) were compared and pathologic findings of the full layer were evaluated. Molecular analysis revealed that the number of dermal fibroblasts was significantly higher in C+ group as compared with C− group. The dermal fibroblasts from C+ group showed more than two-fold increase in the migration ability as compared with the fibroblasts from C− group. The expression of matrix metallopeptidase 9 was increased by more than two-fold and a significant increase in transforming growth factor beta 1 expression and Smad2/3 phosphorylation level was observed in C+ group. C+ group showed more extensive lymphoplasmacytic infiltration with thicker fibrosis and occasional “proliferating core collagen” as compared with C− group. Thus, −79 °C spray-type cryotherapy is ineffective as a monotherapy and should be used in combination with intralesional corticosteroids or botulinum toxin A for favourable outcomes in the treatment of thick keloids. PMID:29186868

Treatment of hypertrophic scars and keloids using intense pulsed light (IPL).

PubMed

Erol, O Onur; Gurlek, Ali; Agaoglu, Galip; Topcuoglu, Ela; Oz, Hayat

2008-11-01

Keloids and hypertrophic scars are extremely disturbing to patients, both physically and psychologically. This study prospectively assessed the safety and efficacy of intense pulsed light (IPL) on scars originating from burns, trauma, surgery, and acne. Hypertrophic scars in 109 patients, originating from surgical incisions (n = 55), traumatic cuts (traffic accidents) (n = 24), acne scars (n = 6), keloids (n = 5), and burns (n = 19), were treated using an IPL Quantum device. Treatment was administered at 2-4-week intervals, and patients received an average of 8 treatments (range = 6-24). Using digital photographs, Changes in scar appearance were assessed by two physicians who were blinded to the study patients and treatments. The photographs were graded on a scale of 0 to 4 (none, minimal, moderate, good, excellent) for improvement in overall clinical appearance and reduction in height, erythema, and hardness. An overall clinical improvement in the appearance of scars and reductions in height, erythema, and hardness were seen in the majority of the patients (92.5%). Improvement was excellent in 31.2% of the patients, good in 25.7%, moderate in 34%, and minimal in 9.1%. Over half the patients had good or excellent improvement. In the preventive IPL treatment group, 65% had good to excellent improvement in clinical appearance. Patient satisfaction was very high. This study suggests that IPL is effective not only in improving the appearance of hypertrophic scars and keloids regardless of their origin, but also in reducing the height, redness, and hardness of scars.

Intralesional cryotherapy versus excision and corticosteroids or brachytherapy for keloid treatment: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Keloids are a burden for patients due to physical, aesthetic and social complaints and treatment remains a challenge because of therapy resistance and high recurrence rates. The main goal of treatment is to improve the quality of life (QoL); this implies that, apart from surgical outcomes, patient-reported outcome measures (PROMs) need to be taken into account. Decision making in keloid treatment is difficult due to heterogeneity of the condition and the lack of comparative studies. Methods/Design This is a multicentre, randomised controlled open trial that compares 1) intralesional cryotherapy versus excision and corticosteroids for primary keloids, and 2) intralesional cryotherapy versus excision and brachytherapy for therapy-resistant keloids. The primary outcome is the Patient and Observer Scar Assessment Scale (POSAS), a 12-item scale (with score 12 indicating the best and 120 indicating the worst scar imaginable). A difference of six points on the total score is considered to be of clinical importance. Secondary outcomes are recurrence rates, volume reduction, Skindex-29 scores, SF-36 scores and complication rates. Primary and secondary outcome measurements are taken at baseline, and at 2, 12, 26 and 52 weeks postoperatively. For analysis, a linear mixed model is used. A total of 176 patients will be included over a period of 2.5 years. The protocol is approved by the Medical Ethics Committee of the Erasmus University Medical Centre Rotterdam and follows good clinical practice guidelines. Discussion The outcomes of this study will improve evidence-based decision making for the treatment of keloids, as well as patient education. Trial registration Dutch Trial Register NTR4151. PMID:24354714

Hypertrophic scars and keloids in surgery: current concepts.

PubMed

Song, Colin

2014-09-01

Hypertrophic scars and keloids remain a challenge in surgery. We appreciate that our understanding of the process at cellular and molecular level, profound as it is, when it comes to the clinical evidence much is left to be desired. Although the bench to bedside conundrum remains, the science of translational research calls for an even higher level of cooperation between the scientist and the clinician for the impetus to succeed.The clinicians alerted us to the possible theories in the pathogenesis of keloid formation, inter alia, the ischemia theory, mast cell theory, immune theory, transforming growth factor β interaction, mechanical theory, and the melanocyte stimulating hormone theory. All of the above presupposed a stimulus that would result in an uncontrolled upregulation of collagen and extracellular matrix expression in the pathogenesis of the keloid. This bedside to bench initiative, as in true science, realized more ponderables than possibilities.By the same token, research into the epidermal-mesenchymal signaling, molecular biology, genomics, and stem cell research holds much promise in the bench top arena. To assess efficacy, many scar assessment scores exist in the literature. The clinical measurement of scar maturity can aid in determining end points for therapeutics. Tissue oxygen tension and color assessment of scars by standardized photography proved to be useful.In surgery, the use of dermal substitutes holds some promise as we surmise that quality scars that arise from dermal elements, molecular and enzyme behavior, and balance. Although a systematic review shows some benefit for earlier closure and healing of wounds, no such review exists at this point in time for the use of dermal substitutes in scars.Adipose-derived stem cell, as it pertains to scars, will hopefully realize the potential of skin regeneration rather than by repair in which we are familiar with as well as the undesirable scarring as a result of healing through the inflammatory

Noninvasive evaluation of collagen and hemoglobin contents and scattering property of in vivo keloid scars and normal skin using diffuse reflectance spectroscopy: pilot study

NASA Astrophysics Data System (ADS)

Tseng, Sheng-Hao; Hsu, Chao-Kai; Yu-Yun Lee, Julia; Tzeng, Shih-Yu; Chen, Wan-Rung; Liaw, Yu-Kai

2012-07-01

Collagen is a rich component in skin that provides skin structure integrity; however, its contribution to the absorption and scattering properties of various types of skin has not been extensively studied. We considered the contribution of the collagen to the absorption spectrum of in vivo normal skin and keloids of 12 subjects derived from our diffuse reflectance spectroscopy (DRS) system in the wavelength range from 550 to 860 nm. It was found that the collagen concentration, the hemoglobin oxygen saturation, and the reduced scattering coefficient of keloids were remarkably different from that of normal skin. Our results suggest that our DRS system could assist clinicians in understanding the functional and structural condition of keloid scars. In the future, we will evaluate the accuracy of our system in the keloid diagnosis and investigate the applicability of our system for other skin-collagen-related studies.

Comparison of different laser systems in the treatment of hypertrophic and atrophic scars and keloids

NASA Astrophysics Data System (ADS)

Scharschmidt, D.; Algermissen, Bernd; Willms-Jones, J.-C.; Philipp, Carsten M.; Berlien, Hans-Peter

1997-12-01

Different laser systems and techniques are used for the treatment of hypertrophic scars, keloids and acne scars. Significant criteria in selecting a suitable laser system are the scar's vascularization, age and diameter. Flashlamp- pumped dye-lasers, CO2-lasers with scanner, Argon and Nd:YAG-lasers are used. Telangiectatic scars respond well to argon lasers, erythematous scars and keloids to dye-laser treatment. Using interstitial Nd:YAG-laser vaporization, scars with a cross-section over 1 cm can generally be reduced. For the treatment of atrophic and acne scars good cosmetic results are achieved with a CO2-laser/scanner system, which allows a precise ablation of the upper dermis with low risk of side-effects.

Bethlem myopathy: An autosomal dominant myopathy with flexion contractures, keloids, and follicular hyperkeratosis.

PubMed

Saroja, Aralikatte Onkarappa; Naik, Karkal Ravishankar; Nalini, Atcharayam; Gayathri, Narayanappa

2013-10-01

Bethlem myopathy and Ullrich congenital muscular dystrophy form a spectrum of collagenopathies caused by genetic mutations encoding for any of the three subunits of collagen VI. Bethlem phenotype is relatively benign and is characterized by proximal dominant myopathy, keloids, contractures, distal hyperextensibility, and follicular hyperkeratosis. Three patients from a single family were diagnosed to have Bethlem myopathy based on European Neuromuscular Centre Bethlem Consortium criteria. Affected father and his both sons had slowly progressive proximal dominant weakness and recurrent falls from the first decade. Both children aged 18 and 20 years were ambulant at presentation. All had flexion contractures, keloids, and follicular hyperkeratosis without muscle hypertrophy. Creatinine kinase was mildly elevated and electromyography revealed myopathic features. Muscle imaging revealed severe involvement of glutei and vasti with "central shadow" in rectus femoris. Muscle biopsy in the father showed dystrophic changes with normal immmunostaining for collagen VI, sarcoglycans, and dysferlin.

On the conservation laws and solutions of a (2+1) dimensional KdV-mKdV equation of mathematical physics

NASA Astrophysics Data System (ADS)

Motsepa, Tanki; Masood Khalique, Chaudry

2018-05-01

In this paper, we study a (2+1) dimensional KdV-mKdV equation, which models many physical phenomena of mathematical physics. This equation has two integral terms in it. By an appropriate substitution, we convert this equation into two partial differential equations, which do not have integral terms and are equivalent to the original equation. We then work with the system of two equations and obtain its exact travelling wave solutions in form of Jacobi elliptic functions. Furthermore, we employ the multiplier method to construct conservation laws for the system. Finally, we revert the results obtained into the original variables of the (2+1) dimensional KdV-mKdV equation.

Comparison of Intralesional Triamcinolone Acetonide, 5-Fluorouracil, and Their Combination for the Treatment of Keloids

PubMed Central

Srivastava, Sunil; Patil, Aditya Nanasaheb; Prakash, Chaitra; Kumari, Hiranmayi

2017-01-01

Objective: Despite the myriad options available, there is no universally accepted treatment for keloids. Our objective was to compare three regimens and establish superiority in terms of objective and subjective outcomes. Approach: In this randomized parallel group study, 60 patients were enrolled and randomly allocated to three groups. Patients received intralesional injections of triamcinolone acetonide (TAC) in Group TAC, 5-fluorouracil (5FU) in Group 5FU, and a combination in Group T + F every 3 weeks till 24 weeks or till the keloid resolved. Results: There was a reduction in all parameters at every successive assessment in all three groups. Improvement in terms of height, vascularity, and pliability was fastest with 5FU, TAC, and T + F group, respectively, which was statistically significant. Decrease in pigmentation was significantly faster with T+F. Reduction in pruritus, however, was significantly faster with 5FU than the other groups, but the difference in reduction of pain among the three groups was not significant. Telangiectasias and skin atrophy were seen most commonly in TAC group, while skin ulceration was a common problem in 5FU group. Conclusion: TAC, 5FU, and their combination are all effective in keloid scars. A combination of TAC +5FU seems to offer the balanced benefit of faster and more efficacious response with lesser adverse effects when compared to individual drugs. PMID:29098115

Up-to-date approach to manage keloids and hypertrophic scars: A useful guide

PubMed Central

Arno, Anna I.; Gauglitz, Gerd G.; Barret, Juan P.; Jeschke, Marc G.

2014-01-01

Keloids and hypertrophic scars occur anywhere from 30 to 90% of patients, and are characterized by pathologically excessive dermal fibrosis and aberrant wound healing. Both entities have different clinical and histochemical characteristics, and unfortunately still represent a great challenge for clinicians due to lack of efficacious treatments. Current advances in molecular biology and genetics reveal new preventive and therapeutical options which represent a hope to manage this highly prevalent, chronic and disabling problem, with long-term beneficial outcomes and improvement of quality of life. While we wait for these translational clinical products to be marketed, however, it is imperative to know the basics of the currently existing wide array of strategies to deal with excessive scars: from the classical corticotherapy, to the most recent botulinum toxin and lasers. The main aim of this review paper is to offer a useful up-to-date guideline to prevent and treat keloids and hypertrophic scars. PMID:24767715

Up-to-date approach to manage keloids and hypertrophic scars: a useful guide.

PubMed

Arno, Anna I; Gauglitz, Gerd G; Barret, Juan P; Jeschke, Marc G

2014-11-01

Keloids and hypertrophic scars occur anywhere from 30 to 90% of patients, and are characterized by pathologically excessive dermal fibrosis and aberrant wound healing. Both entities have different clinical and histochemical characteristics, and unfortunately still represent a great challenge for clinicians due to lack of efficacious treatments. Current advances in molecular biology and genetics reveal new preventive and therapeutical options which represent a hope to manage this highly prevalent, chronic and disabling problem, with long-term beneficial outcomes and improvement of quality of life. While we wait for these translational clinical products to be marketed, however, it is imperative to know the basics of the currently existing wide array of strategies to deal with excessive scars: from the classical corticotherapy, to the most recent botulinum toxin and lasers. The main aim of this review paper is to offer a useful up-to-date guideline to prevent and treat keloids and hypertrophic scars. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Treatment of keloids and hypertrophic scars with dermojet injections of bleomycin: a preliminary study.

PubMed

Saray, Yasemin; Güleç, A Tülin

2005-09-01

Numerous treatment modalities have been used to treat keloids and hypertrophic scars, but the optimal treatment has not been established. The aim of this study was to determine the efficacy and safety of intralesional jet injection of bleomycin as therapy for keloids and hypertrophic scars that are unresponsive to intralesional steroid injection. The study included 14 patients with 15 keloids or hypertrophic scars that had not responded to a minimum of three intralesional injections of triamcinolone acetonide. Multiple jet injections of 0.1 ml of bleomycin (1.5 IU/ml) were administered to each lesion, with injection sites spaced 0.5 mm apart. Injections were repeated each month. Scar height was measured, and scar pliability and erythema were scored at baseline and then monthly during the treatment and follow-up periods. Patients' self-assessments of subjective symptoms (pruritus and pain) were also scored. Clinical improvement was defined primarily on the basis of scar height reduction (percentage reduction from baseline), and was classified using the following scale: complete flattening (100%), highly significant flattening (> 90%), significant flattening (75-90%), moderate flattening (50-75%), and minimal flattening (< 50%). Pre- and post-treatment mean values for scar height, scar pliability, erythema, pruritus and pain were statistically compared. The number of sessions required to successfully treat the lesions ranged from two to six. Eleven lesions (73.3%) showed complete flattening, one (6.7%) showed highly significant flattening, two (13.3%) showed significant flattening, and one scar (6.7%) showed moderate flattening. The mean scar height was significantly lower, and the mean scores for scar pliability and erythema were significantly better at the end of treatment (P < 0.001, P < 0.001 and P < 0.001, respectively). The mean scores for pruritus and pain also improved significantly (P < 0.001 and P = 0.01, respectively). The observed side-effects were

Unilateral congenital corneal keloid with anterior segment mesenchymal dysgenesis and subluxated lens: case report and review of literature.

PubMed

Vanathi, M; Sen, Seema; Panda, Anita; Dada, Tanuj; Behera, Geeta; Khokhar, Sudharshan

2007-01-01

To report the unusual association of unilateral congenital corneal keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens. A 20-year old man presented with a mass lesion involving the left cornea. The corneal lesion had been present since birth. On biomicroscopic examination, a well-defined vascularized, grayish-white mass occupying the whole of the left cornea was seen. The right eye showed multiple peripheral corneal opacities with iridocorneal adhesions, a poorly defined supranasal limbus, and a subluxated lens. Excision biopsy of the mass was done for histopathologic examination. Histopathologic examination of the excised corneal mass showed features consistent with that of a corneal keloid: thickened keratinized epithelium, absent Bowman membrane layer, and fibrovascular hyperplasia composed of hyalinized collagen fibers with irregular orientation of the collagen lamellae. During penetrating keratoplasty of the left eye, an anomalous iris pattern with poorly defined angle and a supranasal subluxated lens was also observed. Extraction of the subluxated lens was also done. The graft failed subsequent to a nonhealing persistent epithelial defect. Our case report highlights the rare association of a unilateral congenital corneal keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens.

Bilinear approach to Kuperschmidt super-KdV type equations

NASA Astrophysics Data System (ADS)

Babalic, Corina N.; Carstea, A. S.

2018-06-01

Hirota bilinear form and soliton solutions for the super-KdV (Korteweg–de Vries) equation of Kuperschmidt (Kuper–KdV) are given. It is shown that even though the collision of supersolitons is more complicated than in the case of the supersymmetric KdV equation of Manin–Radul, the asymptotic effect of the interaction is simpler. As a physical application it is shown that the well-known FPU problem, having a phonon-mediated interaction of some internal degrees of freedom expressed through Grassmann fields, transforms to the Kuper–KdV equation in a multiple-scale approach.

Classification of Dark Modified KdV Equation

NASA Astrophysics Data System (ADS)

Xiong, Na; Lou, Sen-Yue; Li, Biao; Chen, Yong

2017-07-01

The dark Korteweg-de Vries (KdV) systems are defined and classified by Kupershmidt sixteen years ago. However, there is no other classifications for other kinds of nonlinear systems. In this paper, a complete scalar classification for dark modified KdV (MKdV) systems is obtained by requiring the existence of higher order differential polynomial symmetries. Different to the nine classes of the dark KdV case, there exist twelve independent classes of the dark MKdV equations. Furthermore, for the every class of dark MKdV system, there is a free parameter. Only for a fixed parameter, the dark MKdV can be related to dark KdV via suitable Miura transformation. The recursion operators of two classes of dark MKdV systems are also given. Supported by the Global Change Research Program of China under Grant No. 2015Cb953904, National Natural Science Foundation of China under Grant Nos. 11675054, 11435005, 11175092, and 11205092 and Shanghai Knowledge Service Platform for Trustworthy Internet of Things (No. ZF1213) and K. C. Wong Magna Fund in Ningbo University

Comparative effect of topical silicone gel and topical tretinoin cream for the prevention of hypertrophic scar and keloid formation and the improvement of scars.

PubMed

Kwon, S Y; Park, S D; Park, K

2014-08-01

Numerous modalities have been used to treat keloids and hypertrophic scars; however, optimal treatment has not yet been established. Therefore, prevention is the mainstay. Recently, silicone gel and tretinoin cream have been shown to be useful for the prevention of hypertrophic scars and keloids. However, there has been no comparative study of the two topical agents thus far. To determine and compare the effectiveness of silicone gel and tretinoin cream for the prevention of hypertrophic scars and keloids resulting from postoperative wounds and for scar improvement. This study included 26 patients with 44 different wounds. The postoperative wounds were divided into two treatment groups and one control group. The patients in the first and second treatment group applied silicone gel and tretinoin cream, respectively, twice a day on their wounds after their stitches were removed. In contrast, the control group patients did not apply anything. We used the Modified Vancouver Scar Scale to quantitatively examine the effectiveness of silicone gel and tretinoin cream just after stitches removal, and at 4, 8, 12 and 24 weeks after removal of the stitches. The silicone gel and tretinoin cream effectively prevented hypertrophic scars and keloids and improved scar effects in the two treatment groups compared with those in the control group. However, no significant difference was noted between the two treatment groups. To prevent hypertrophic scars and keloids and improve scars after surgery, application of a silicone gel or a tretinoin cream to the wounds is needed. © 2013 European Academy of Dermatology and Venereology.

Hamiltonian formulation of the KdV equation

NASA Astrophysics Data System (ADS)

Nutku, Y.

1984-06-01

We consider the canonical formulation of Whitham's variational principle for the KdV equation. This Lagrangian is degenerate and we have found it necessary to use Dirac's theory of constrained systems in constructing the Hamiltonian. Earlier discussions of the Hamiltonian structure of the KdV equation were based on various different decompositions of the field which is avoided by this new approach.

Decreasing Kd uncertainties through the application of thermodynamic sorption models.

PubMed

Domènech, Cristina; García, David; Pękala, Marek

2015-09-15

Radionuclide retardation processes during transport are expected to play an important role in the safety assessment of subsurface disposal facilities for radioactive waste. The linear distribution coefficient (Kd) is often used to represent radionuclide retention, because analytical solutions to the classic advection-diffusion-retardation equation under simple boundary conditions are readily obtainable, and because numerical implementation of this approach is relatively straightforward. For these reasons, the Kd approach lends itself to probabilistic calculations required by Performance Assessment (PA) calculations. However, it is widely recognised that Kd values derived from laboratory experiments generally have a narrow field of validity, and that the uncertainty of the Kd outside this field increases significantly. Mechanistic multicomponent geochemical simulators can be used to calculate Kd values under a wide range of conditions. This approach is powerful and flexible, but requires expert knowledge on the part of the user. The work presented in this paper aims to develop a simplified approach of estimating Kd values whose level of accuracy would be comparable with those obtained by fully-fledged geochemical simulators. The proposed approach consists of deriving simplified algebraic expressions by combining relevant mass action equations. This approach was applied to three distinct geochemical systems involving surface complexation and ion-exchange processes. Within bounds imposed by model simplifications, the presented approach allows radionuclide Kd values to be estimated as a function of key system-controlling parameters, such as the pH and mineralogy. This approach could be used by PA professionals to assess the impact of key geochemical parameters on the variability of radionuclide Kd values. Moreover, the presented approach could be relatively easily implemented in existing codes to represent the influence of temporal and spatial changes in geochemistry

Delayed allergic dermatitis presenting as a keloid-like reaction caused by sting from an Indo-Pacific Portuguese man-o'-war (Physalia utriculus).

PubMed

Guevara, B E K; Dayrit, J F; Haddad, V

2017-03-01

Cnidarian envenomations are common occurrences in the tropics that can affect holidaymakers. The cutaneous reactions are classified as immediate or delayed types. Delayed allergic reactions are persistently recurring dermatitis, which can occur within 1-4 weeks from the initial sting, and may last for several months. Hypertrophic scar-like or keloid-like reactions are rare, and are believed to be a type IV hypersensitivity reaction to sequestered antigens from stinging filaments. We report an unusual case of delayed allergic dermatitis with keloid-like presentation caused by Physalia utriculus. © 2017 British Association of Dermatologists.

The King-Devick (K-D) test of rapid eye movements: a bedside correlate of disability and quality of life in MS.

PubMed

Moster, Stephen; Wilson, James A; Galetta, Steven L; Balcer, Laura J

2014-08-15

We investigated the King-Devick (K-D) test of rapid number naming as a visual performance measure in a cohort of patients with multiple sclerosis (MS). In this cross-sectional study, 81 patients with MS and 20 disease-free controls from an ongoing study of visual outcomes underwent K-D testing. A test of rapid number naming, K-D requires saccadic eye movements as well as intact vision, attention and concentration. To perform the K-D test, participants are asked to read numbers aloud as quickly as possible from three test cards; the sum of the three test card times in seconds constitutes the summary score. High-contrast visual acuity (VA), low-contrast letter acuity (1.25% and 2.5% levels), retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT), MS Functional Composite (MSFC) and vision-specific quality of life (QOL) measures (25-Item NEI Visual Functioning Questionnaire [NEI-VFQ-25] and 10-Item Neuro-Ophthalmic Supplement) were also assessed. K-D time scores in the MS cohort (total time to read the three test cards) were significantly higher (worse) compared to those for disease-free controls (P=0.003, linear regression, accounting for age). Within the MS cohort, higher K-D scores were associated with worse scores for the NEI-VFQ-25 composite (P<0.001), 10-Item Neuro-Ophthalmic Supplement (P<0.001), binocular low-contrast acuity (2.5%, 1.25%, P<0.001, and high-contrast VA (P=0.003). Monocular low-contrast vision scores (P=0.001-0.009) and RNFL thickness (P=0.001) were also reduced in eyes of patients with worse K-D scores (GEE models accounting for age and within-patient, inter-eye correlations). Patients with a history of optic neuritis (ON) had increased (worse) K-D scores. Patients who classified their work disability status as disabled (receiving disability pension) did worse on K-D testing compared to those working full-time (P=0.001, accounting for age). The K-D test, a <2 minute bedside test of rapid number naming, is associated

7 CFR 29.1080 - Variegated dark red (KD).

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Variegated dark red (KD). 29.1080 Section 29.1080..., 13, 14 and Foreign Type 92) § 29.1080 Variegated dark red (KD). A dark brownish-red discoloration... over extended periods of time. Any leaf of which 20 percent or more of its surface is dark brownish-red...

7 CFR 29.1080 - Variegated dark red (KD).

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Variegated dark red (KD). 29.1080 Section 29.1080..., 13, 14 and Foreign Type 92) § 29.1080 Variegated dark red (KD). A dark brownish-red discoloration... over extended periods of time. Any leaf of which 20 percent or more of its surface is dark brownish-red...

7 CFR 29.1080 - Variegated dark red (KD).

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Variegated dark red (KD). 29.1080 Section 29.1080..., 13, 14 and Foreign Type 92) § 29.1080 Variegated dark red (KD). A dark brownish-red discoloration... over extended periods of time. Any leaf of which 20 percent or more of its surface is dark brownish-red...

7 CFR 29.1080 - Variegated dark red (KD).

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Variegated dark red (KD). 29.1080 Section 29.1080..., 13, 14 and Foreign Type 92) § 29.1080 Variegated dark red (KD). A dark brownish-red discoloration... over extended periods of time. Any leaf of which 20 percent or more of its surface is dark brownish-red...

High-Mobility Group Box 1 Mediates Fibroblast Activity via RAGE-MAPK and NF-κB Signaling in Keloid Scar Formation.

PubMed

Kim, Jihee; Park, Jong-Chul; Lee, Mi Hee; Yang, Chae Eun; Lee, Ju Hee; Lee, Won Jai

2017-12-28

Emerging studies have revealed the involvement of high-mobility group box 1 (HMGB1) in systemic fibrotic diseases, yet its role in the cutaneous scarring process has not yet been investigated. We hypothesized that HMGB1 may promote fibroblast activity to cause abnormal cutaneous scarring. In vitro wound healing assay with normal and keloid fibroblasts demonstrated that HMGB1 administration promoted the migration of both fibroblasts with increased speed and a greater traveling distance. Treatment of the HMGB1 inhibitor glycyrrhizic acid (GA) showed an opposing effect on both activities. To analyze the downstream mechanism, the protein levels of extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were measured by western blot analysis. HMGB1 increased the expression levels of ERK1/2, AKT, and NF-κB compared to the control, which was suppressed by GA. HMGB1 promoted both normal and keloid fibroblasts migration to a degree equivalent to that achieved with TGF-β. We concluded that HMGB1 activates fibroblasts via the receptor for advanced glycation end product (RAGE)-mitogen-activated protein kinases (MAPK) and NF-κB interaction signaling pathways. Further knowledge of the relationship of HMGB1 with skin fibrosis may lead to a promising clinical approach to manage abnormal scarring.

Noninvasive laser therapy in the treatment of keloid scar after injury caused by a jellyfish: a case report

NASA Astrophysics Data System (ADS)

Kymplova, Jaroslava; Navratil, Leos; Skopek, Jiri

2001-10-01

Keloid scars trouble the patients particularly for aesthetical reasons. They also frequency result in various functional disturbances, they are painful and the patient suffers for dysesthesia on touch. Low level laser is able to provide three principal effects: biostimulating, analgesic and antiinflammatory. Particularly thanks to the first two effects we are able, when adhering to the proper therapeutic procedure, to moderate or even remove the above mentioned problems. We complement the low level laser treatment by applications of ointments, cremes or silicone strips. Our communication is aimed at a case report concerning the treatment of keloid scars resulting from an injury by a jellyfish with the aim to familiarize the reader with wide therapeutic possibilities of non-invasive laser, even in indications which are not frequently encountered in central Europe.

Wound-healing and potential anti-keloidal properties of the latex of Calotropis procera (Aiton) Asclepiadaceae in rabbits.

PubMed

Aderounmu, A O; Omonisi, A E; Akingbasote, J A; Makanjuola, M; Bejide, R A; Orafidiya, L O; Adelusola, K A

2013-01-01

Calotropis Procera (CP) has been used in the management of toothache, fresh skin burns, gum bleeding as well as others to make it qualify as a medicinal plant. This study was designed to assess its wound-healing property in rabbits and its potentials for anti keloidal activity.Fresh latex of Calotropis were obtained and evaluated phytochemically. Fifteen male rabbits were used and four excisional wounds were created on each rabbit. The rabbits were divided into five groups of three each. Group 1 was the negative control and received no treatment. The wounds of group 2 animals were treated with 2mL of Calotropis latex; group 3 with 2mL honey; and group 4 with a mixture of 1ml honey and 1 mL of the latex. The animals in group 5 were given 2mg triamcinolone intramuscularly. All the groups had their wounds treated daily for 21 days. The wounds' diameters were measured on the day of wound creation, thereafter on days 7, 14 and 21 post wound creation. Biopsies of the wounds were taken on days 3 and 21 and viewed histologically. Phytochemical study of the latex revealed the presence of glycosides, tannins and alkaloids. The wounds were found to be significantly (p<0.05) reduced in groups treated with 50% latex in honey and triamcinolone, respectively, on day 7 post wound creation while there was a significant (p<0.05) reduction in wound surface area in all treated groups on days 14 and 21 post wound creation. Histological findings in untreated group showed thick bundle of collagen fibres some of which had broad based configurations, reminiscent of keloid. The group treated with 2mL of Calotropis latex revealed the presence of florid granulation tissues on day 3 while there was a marked reduction in quantity and size of collagen fibres on day 21 post wound creation which was comparable with what was seen for the triamcinolone-treated group.The general effect of Calotropis latex on wound-healing was noted. Likewise it's similarity to that of triamcinolone, an anti-keloidal

Vaccines and Kawasaki disease.

PubMed

Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

2016-01-01

The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

Self-adhesive silicone gel sheet: a treatment for hypertrophic scars and keloids.

PubMed

Chuangsuwanich, A; Osathalert, V; Muangsombut, S

2000-04-01

An open clinical trial was conducted to assess the effect of self-adhesive silicone gel sheet (SASGS) for the treatment of hypertrophic scars and keloids in Thai people. Patients were instructed to apply the SASGS to the scars as long as possible, but not less than 12 hours per day for at least 8 weeks. The subjective results of the treatment were evaluated by the patients. The scars were evaluated for color, height, weight before and after treatment at 4 and 8 weeks. Eighteen patients with 18 hypertrophic scars or keloids were recruited into the study. Their ages ranged from 6 to 33 years (mean 21 years). The average duration of the scars was 5.7 years. Twelve patients (66.67%) stated good results. All of the 18 patients wanted to continue the treatment with SASGS. Heights of the scars were reduced in 12 lesions (66.67%) after treatment for 8 weeks (P = 0.058). Weights of the lesions were decreased in 10 lesions (55.55%) but were not statistically different (P = 0.090). Seven lesions (36.84%) were improved in color. Two patients (11.11%) developed erythematous rash around the lesions which subsided after withdrawal of the treatment. The long term follow-up for the recurrence and the mechanism of action of this treatment should be studied further.

A novel noncommutative KdV-type equation, its recursion operator, and solitons

NASA Astrophysics Data System (ADS)

Carillo, Sandra; Lo Schiavo, Mauro; Porten, Egmont; Schiebold, Cornelia

2018-04-01

A noncommutative KdV-type equation is introduced extending the Bäcklund chart in Carillo et al. [Symmetry Integrability Geom.: Methods Appl. 12, 087 (2016)]. This equation, called meta-mKdV here, is linked by Cole-Hopf transformations to the two noncommutative versions of the mKdV equations listed in Olver and Sokolov [Commun. Math. Phys. 193, 245 (1998), Theorem 3.6]. For this meta-mKdV, and its mirror counterpart, recursion operators, hierarchies, and an explicit solution class are derived.

Tissue-specific expression of the gene coding for human Clara cell 10-kD protein, a phospholipase A2-inhibitory protein.

PubMed Central

Peri, A; Cordella-Miele, E; Miele, L; Mukherjee, A B

1993-01-01

Clara cell 10-kD protein (cc10kD), a secretory phospholipase A2 inhibitor, is suggested to be the human counterpart of rabbit uteroglobin (UG). Because cc10kD is expressed constitutively at a very high level in the human respiratory epithelium, the 5' region of its gene may be useful in achieving organ-specific expression of recombinant DNA in gene therapy of diseases such as cystic fibrosis. However, it is important to establish the tissue-specific expression of this gene before designing gene transfer experiments. Since the UG gene in the rabbit is expressed in many other organs besides the lung and the endometrium, we investigated the organ and tissue specificity of human cc10kD gene expression using polymerase chain reaction, nucleotide sequence analysis, immunofluorescence, and Northern blotting. Our results indicate that, in addition to the lung, cc10kD is expressed in several nonrespiratory organs, with a distribution pattern very similar, if not identical, to that of UG in the rabbit. These results underscore the necessity for more detailed analyses of the 5' region of the human cc10kD gene before its usefulness in gene therapy could be fully assessed. These data also suggest that cc10kD and UG may have similar physiological function(s). Images PMID:8227325

A Super mKdV Equation: Bosonization, Painlevé Property and Exact Solutions

NASA Astrophysics Data System (ADS)

Ren, Bo; Lou, Sen-Yue

2018-04-01

The symmetry of the fermionic field is obtained by means of the Lax pair of the mKdV equation. A new super mKdV equation is constructed by virtue of the symmetry of the fermionic form. The super mKdV system is changed to a system of coupled bosonic equations with the bosonization approach. The bosonized SmKdV (BSmKdV) equation admits Painlevé property by the standard singularity analysis. The traveling wave solutions of the BSmKdV system are presented by the mapping and deformation method. We also provide other ideas to construct new super integrable systems. Supported by the National Natural Science Foundation of China under Grant Nos. 11775146, 11435005, and 11472177, Shanghai Knowledge Service Platform for Trustworthy Internet of Things under Grant No. ZF1213 and K. C. Wong Magna Fund in Ningbo University

Efficient Delaunay Tessellation through K-D Tree Decomposition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morozov, Dmitriy; Peterka, Tom

Delaunay tessellations are fundamental data structures in computational geometry. They are important in data analysis, where they can represent the geometry of a point set or approximate its density. The algorithms for computing these tessellations at scale perform poorly when the input data is unbalanced. We investigate the use of k-d trees to evenly distribute points among processes and compare two strategies for picking split points between domain regions. Because resulting point distributions no longer satisfy the assumptions of existing parallel Delaunay algorithms, we develop a new parallel algorithm that adapts to its input and prove its correctness. We evaluatemore » the new algorithm using two late-stage cosmology datasets. The new running times are up to 50 times faster using k-d tree compared with regular grid decomposition. Moreover, in the unbalanced data sets, decomposing the domain into a k-d tree is up to five times faster than decomposing it into a regular grid.« less

Studying intense pulsed light method along with corticosteroid injection in treating keloid scars.

PubMed

Shamsi Meymandi, Simin; Rezazadeh, Azadeh; Ekhlasi, Ali

2014-02-01

Results of various studies suggest that the hypertrophic and keloid scars are highly prevalent in the general population and are irritating both physically and mentally. Considering the variety of existing therapies, intense pulsed light (IPL) method along with corticosteroid injection was evaluated in treating these scars. 86 subjects were included in this clinical trial. Eight sessions of therapeutic intervention were done with IPL along with corticosteroid intralesional injection using 450 to 1200 NM filter, Fluence 30-40 J/cm2, pulse duration of 2.1-10 ms and palsed delay 10-40 ms with an interval of three weeks. To specify the recovery consequences and complication rate and to determine features of the lesion, the criteria specified in the study of Eroll and Vancouver scar scale were used. The level of clinical improvement, color improvement and scar height was 89.1%, 88.8% and 89.1% respectively. The incidence of complications (1 telangiectasia case, 7 hyperpigmentation cases and 2 atrophy cases) following treatment with IPL was 11.6%. Moreover, the participants' satisfaction with IPL method was 88.8%. This study revealed that a combined therapy (intralesional corticosteroid injection + IPL) increases the recovery level of hypertrophic and keloid scars. It was also demonstrated that this method had no significant side effect and patients were highly satisfied with this method.

Studying Intense Pulsed Light Method Along With Corticosteroid Injection in Treating Keloid Scars

PubMed Central

Shamsi Meymandi, Simin; Rezazadeh, Azadeh; Ekhlasi, Ali

2014-01-01

Background: Results of various studies suggest that the hypertrophic and keloid scars are highly prevalent in the general population and are irritating both physically and mentally. Objective: Considering the variety of existing therapies, intense pulsed light (IPL) method along with corticosteroid injection was evaluated in treating these scars. Materials and Methods: 86 subjects were included in this clinical trial. Eight sessions of therapeutic intervention were done with IPL along with corticosteroid intralesional injection using 450 to 1200 NM filter, Fluence 30-40 J/cm2, pulse duration of 2.1-10 ms and palsed delay 10-40 ms with an interval of three weeks. To specify the recovery consequences and complication rate and to determine features of the lesion, the criteria specified in the study of Eroll and Vancouver scar scale were used. Results: The level of clinical improvement, color improvement and scar height was 89.1%, 88.8% and 89.1% respectively. The incidence of complications (1 telangiectasia case, 7 hyperpigmentation cases and 2 atrophy cases) following treatment with IPL was 11.6%. Moreover, the participants’ satisfaction with IPL method was 88.8%. Conclusions: This study revealed that a combined therapy (intralesional corticosteroid injection + IPL) increases the recovery level of hypertrophic and keloid scars. It was also demonstrated that this method had no significant side effect and patients were highly satisfied with this method. PMID:24719725

Recurrent Kawasaki disease: USA and Japan.

PubMed

Maddox, Ryan A; Holman, Robert C; Uehara, Ritei; Callinan, Laura S; Guest, Jodie L; Schonberger, Lawrence B; Nakamura, Yosikazu; Yashiro, Mayumi; Belay, Ermias D

2015-12-01

Descriptive epidemiologic studies of recurrent and non-recurrent Kawasaki disease (KD) may identify other potentially important differences between these illnesses. Data from the USA and Japan, the Centers for Disease Control and Prevention (CDC) national KD surveillance(1984-2008) and the 17th Japanese nationwide survey (2001-2002), respectively, were analyzed to examine recurrent KD patients <18 years of age meeting the CDC KD case or atypical KD case definition. These patients were compared with non-recurrent KD patients. Of the 5557 US KD patients <18 years of age during 1984-2008, 97 (1.7%) were identified as having had recurrent KD. Among the US Asian/Pacific Islander KD patients, 3.5% had recurrent KD, which was similar to the percentage identified among KD patients (3.5%) in the Japanese survey. Compared with non-recurrent KD patients, KD patients [with recurrent KD] were more likely to be older, fulfill the atypical KD case definition, and have coronary artery abnormalities (CAA) despite i.v. immunoglobulin (IVIG) treatment. Differences in the age, race, and frequency of CAA exist between recurrent and non-recurrent KD patients. The increased association of CAA with recurrent KD suggests that more aggressive treatment strategies in conjunction with IVIG may be indicated for the second episode of KD. © 2015 Japan Pediatric Society.

A new integrable equation combining the modified KdV equation with the negative-order modified KdV equation: multiple soliton solutions and a variety of solitonic solutions

NASA Astrophysics Data System (ADS)

Wazwaz, Abdul-Majid

2018-07-01

A new third-order integrable equation is constructed via combining the recursion operator of the modified KdV equation (MKdV) and its inverse recursion operator. The developed equation will be termed the modified KdV-negative order modified KdV equation (MKdV-nMKdV). The complete integrability of this equation is confirmed by showing that it nicely possesses the Painlevé property. We obtain multiple soliton solutions for the newly developed integrable equation. Moreover, this equation enjoys a variety of solutions which include solitons, peakons, cuspons, negaton, positon, complexiton and other solutions.

Lytic and Chemotactic Features of the Plaque-Forming Bacterium KD531 on Phaeodactylum tricornutum

PubMed Central

Chen, Zhangran; Zheng, Wei; Yang, Luxi; Boughner, Lisa A.; Tian, Yun; Zheng, Tianling; Xu, Hong

2017-01-01

Phaeodactylum tricornutum is a dominant bloom forming species and potential biofuel feedstock. To control P. tricornutum bloom or to release lipids from P. tricornutum, we previously screened and identified the lytic bacterium Labrenzia sp. KD531 toward P. tricornutum. In the present study, we evaluated the lytic activity of Labrenzia sp. KD531 on microalgae and investigated its lytic mechanism. The results indicated that the lytic activity of KD531 was temperature- and pH-dependent, but light-independent. In addition to P. tricornutum, KD531 also showed lytic activity against other algal species, especially green algae. A quantitative analysis of algal cellular protein, carbohydrate and lipid content together with measurements of dry weight after exposure to bacteria-infected algal lysate indicated that the bacterium KD531 influenced the algal biomass by disrupting the algal cells. Both chemotactic analysis and microscopic observations of subsamples from different regions of formed plaques showed that KD531 could move toward and then directly contact algal cells. Direct contact between P. tricornutum and KD531 cells was essential for the lytic process. PMID:29312256

Kawasaki disease: A brief history.

PubMed

Burns, J C; Kushner, H I; Bastian, J F; Shike, H; Shimizu, C; Matsubara, T; Turner, C L

2000-08-01

Tomisaku Kawasaki published the first English-language report of 50 patients with Kawasaki disease (KD) in 1974. Since that time, KD has become the leading cause of acquired heart disease among children in North America and Japan. Although an infectious agent is suspected, the cause remains unknown. However, significant progress has been made toward understanding the natural history of the disease and therapeutic interventions have been developed that halt the immune-mediated destruction of the arterial wall. We present a brief history of KD, review progress in research on the disease, and suggest avenues for future study. Kawasaki saw his first case of KD in January 1961 and published his first report in Japanese in 1967. Whether cases existed in Japan before that time is currently under study. The most significant controversy in the 1960s in Japan was whether the rash and fever sign/symptom complex described by Kawasaki was connected to subsequent cardiac complications in a number of cases. Pathologist Noboru Tanaka and pediatrician Takajiro Yamamoto disputed the early assertion of Kawasaki that KD was a self-limited illness with no sequelae. This controversy was resolved in 1970 when the first Japanese nationwide survey of KD documented 10 autopsy cases of sudden cardiac death after KD. By the time of the first English-language publication by Kawasaki in 1974, the link between KD and coronary artery vasculitis was well-established. KD was independently recognized as a new and distinct condition in the early 1970s by pediatricians Marian Melish and Raquel Hicks at the University of Hawaii. In 1973, at the same Hawaiian hospital, pathologist Eunice Larson, in consultation with Benjamin Landing at Los Angeles Children's Hospital, retrospectively diagnosed a 1971 autopsy case as KD. The similarity between KD and infantile periarteritis nodosa (IPN) was apparent to these pathologists, as it had been to Tanaka earlier. What remains unknown is the reason for the

Convective wave breaking in the KdV equation

NASA Astrophysics Data System (ADS)

Brun, Mats K.; Kalisch, Henrik

2018-03-01

The KdV equation is a model equation for waves at the surface of an inviscid incompressible fluid, and it is well known that the equation describes the evolution of unidirectional waves of small amplitude and long wavelength fairly accurately if the waves fall into the Boussinesq regime. The KdV equation allows a balance of nonlinear steepening effects and dispersive spreading which leads to the formation of steady wave profiles in the form of solitary waves and cnoidal waves. While these wave profiles are solutions of the KdV equation for any amplitude, it is shown here that there for both the solitary and the cnoidal waves, there are critical amplitudes for which the horizontal component of the particle velocity matches the phase velocity of the wave. Solitary or cnoidal solutions of the KdV equation which surpass these amplitudes feature incipient wave breaking as the particle velocity exceeds the phase velocity near the crest of the wave, and the model breaks down due to violation of the kinematic surface boundary condition. The condition for breaking can be conveniently formulated as a convective breaking criterion based on the local Froude number at the wave crest. This breaking criterion can also be applied to time-dependent situations, and one case of interest is the development of an undular bore created by an influx at a lateral boundary. It is shown that this boundary forcing leads to wave breaking in the leading wave behind the bore if a certain threshold is surpassed.

K&D Landscaping and Construction Information Sheet

EPA Pesticide Factsheets

K&D Landscaping and Construction (the Company) is located in Cazenovia, New York. The settlement involves renovation activities conducted at property constructed prior to 1978, located in Rochester, New York.

Comparison of single intra operative versus an intra operative and two post operative injections of the triamcinolone after wedge excision of keloids of helix.

PubMed

Bashir, Muhammad Mustehsan; Ahmad, Hazqeel; Yousaf, Nadeem; Khan, Farid Ahmad

2015-07-01

To compare single intra-operative versus an intra-operative and two post-operative injections of triamcinolone after wedge excision of keloids of helix. The randomised controlled trial was conducted at the King Edward Medical University, Lahore, from January, 2011, to March, 2014, and comprised female patients over 14 years of age presenting with post-piercing keloids of helix not treated previously by any means and amenable to wedge excision. The subjects were divided into Group A who were given a single intra-operative injection of triamcinolone, and Group B who had an intra-operative and two post-operative injections of triamcinolone. Extra-lesional wedge excision of keloids was done, followed by infiltration of flaps and wound base with 0.5-1cc of triamcinolone 40mg/cc. Group B patients were given additional injections of triamcinolone at 1st and 2nd monthly visits. Both groups were observed for the evidence of hypertrophy or complications. Development of hypertrophy within one year of completion of treatment was considered recurrence. The 70 patients in the study were divided into two equal groups of 35(50%) each. The mean age of Group A was 22.34±4.95 years and that of Group B was 22.88±4.22 years (p=0.624). The Mean size of the keloids was 2.54±0.516 cm(2) in Group A and 2.61±0.569 cm(2) in Group B (p=0.613). Recurrence rate in Group A was 3(8.5%) and 2(5.7%) in Group B (p= 0.64). The complication rate was 3(8.5%) in Group A and 8(22.8%) in Group B (p=0.10). Single injection of triamcinolone was as effective as three in reducing recurrence with less complication rate.

Rogue periodic waves of the modified KdV equation

NASA Astrophysics Data System (ADS)

Chen, Jinbing; Pelinovsky, Dmitry E.

2018-05-01

Rogue periodic waves stand for rogue waves on a periodic background. Two families of travelling periodic waves of the modified Korteweg–de Vries (mKdV) equation in the focusing case are expressed by the Jacobian elliptic functions dn and cn. By using one-fold and two-fold Darboux transformations of the travelling periodic waves, we construct new explicit solutions for the mKdV equation. Since the dn-periodic wave is modulationally stable with respect to long-wave perturbations, the new solution constructed from the dn-periodic wave is a nonlinear superposition of an algebraically decaying soliton and the dn-periodic wave. On the other hand, since the cn-periodic wave is modulationally unstable with respect to long-wave perturbations, the new solution constructed from the cn-periodic wave is a rogue wave on the cn-periodic background, which generalizes the classical rogue wave (the so-called Peregrine’s breather) of the nonlinear Schrödinger equation. We compute the magnification factor for the rogue cn-periodic wave of the mKdV equation and show that it remains constant for all amplitudes. As a by-product of our work, we find explicit expressions for the periodic eigenfunctions of the spectral problem associated with the dn and cn periodic waves of the mKdV equation.

Recurrent Kawasaki disease, United States and Japan

PubMed Central

Maddox, Ryan A.; Holman, Robert C.; Uehara, Ritei; Callinan, Laura S.; Guest, Jodie L.; Schonberger, Lawrence B.; Nakamura, Yosikazu; Yashiro, Mayumi; Belay, Ermias D.

2015-01-01

Background Descriptive epidemiologic studies of recurrent and non-recurrent Kawasaki disease (KD) may identify other potentially important differences between these illnesses. Methods Data from the United States and Japan, the Centers for Disease Control and Prevention (CDC) national KD surveillance (1984–2008) and the 17th Japanese nationwide survey (2001–2002), respectively, were analyzed to examine recurrent KD patients <18 years of age meeting the CDC KD case or atypical KD case definition. These patients were compared to non-recurrent KD patients. Results Of the 5557 US KD patients <18 years of age during 1984–2008, 97 (1.7%) were identified as having had recurrent KD. Among the US Asian/Pacific Islander KD patients, 3.5% had recurrent KD, which was similar to the percentage identified among KD patients (3.5%) in the Japanese survey. Compared to non-recurrent KD patients, KD patients experiencing a recurrent KD episode were more likely to be older, fulfill the atypical KD case definition, and have coronary artery abnormalities (CAA) despite IVIG treatment. Conclusions Differences in the age, race, and frequency of CAA exist between recurrent and non-recurrent KD patients. The increased association of CAA with recurrent KD suggests that more aggressive treatment strategies in conjunction with IVIG may be indicated for the second episode of KD. PMID:26096590

Predicting the characteristics of the aetiological agent for Kawasaki disease from other paediatric infectious diseases in Japan.

PubMed

Nagao, Y; Urabe, C; Nakamura, H; Hatano, N

2016-02-01

Although Kawasaki disease (KD), which was first reported in the 1960s, is assumed to be infectious, its aetiological agent(s) remains unknown. We compared the geographical distribution of the force of infection and the super-annual periodicity of KD and seven other paediatric infectious diseases in Japan. The geographical distribution of the force of infection, which was estimated as the inverse of the mean patient age, was similar in KD and other paediatric viral infections. This similarity was due to the fact that the force of infection was determined largely by the total fertility rate. This finding suggests that KD shares a transmission route, i.e. sibling-to-sibling infection, with other paediatric infections. The super-annual periodicity, which is positively associated with the sum of an infectious disease's incubation period and infectious period, was much longer for KD and exanthema subitum than other paediatric infectious diseases. The virus for exanthema subitum is known to persist across the host's lifespan, which suggests that the aetiological agent for KD may also be capable of persistent infection. Taken together, these findings suggest that the aetiological agent for KD is transmitted through close contact and persists asymptomatically in most hosts.

Direct Connection between the RII Chain and the Nonautonomous Discrete Modified KdV Lattice

NASA Astrophysics Data System (ADS)

Maeda, Kazuki; Tsujimoto, Satoshi

2013-11-01

The spectral transformation technique for symmetric RII polynomials is developed. Use of this technique reveals that the nonautonomous discrete modified KdV (nd-mKdV) lattice is directly connected with the RII chain. Hankel determinant solutions to the semi-infinite nd-mKdV lattice are also presented.

The King-Devick (K-D) test and concussion diagnosis in semi-professional rugby union players.

PubMed

Molloy, John H; Murphy, Ian; Gissane, Conor

2017-08-01

To determine the utility of the King-Devick (K-D) test in identifying sports-related concussion in semi-professional rugby players. Descriptive cohort study. 176 male players were recruited from a semi-professional rugby union competition in New Zealand (NZ). Baseline K-D scores were obtained in the pre-season. Post-match K-D and Pitch Side Concussion Assessment Version 2 (PSCA2) scores were obtained in those with suspected concussion. Post-match K-D scores were also administered to selected control players. 19 concussions in 18 players were analysed. In addition, 33 controls were used for analysis. A positive K-D test was identified in 53% of players with concussion post-match. Conversely, a positive test was identified in 33% of controls. The sensitivity and specificity of the K-D test was calculated as 53% and 69% respectively. The positive predictive value and negative predictive value was 48% and 73% respectively. The PSCA2 correctly identified 74% of concussions. The K-D test identified 3 cases not identified by the PSCA2. When the PSCA2 and K-D were combined, 89% of concussions were correctly identified. The K-D test does not appear to be effective if used as a stand-alone test for the diagnosis of concussion. However, if used alongside current side-line cognitive and balance tests, it may assist in more accurately diagnosing sports-related concussion. Further research should look to utilise the K-D test in in-match protocols to establish if this improves the diagnostic accuracy of in-match protocols for sports-related concussion. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Prevention of hypertrophic scars and keloids by the prophylactic use of topical silicone gel sheets following a surgical procedure in an office setting.

PubMed

Gold, M H; Foster, T D; Adair, M A; Burlison, K; Lewis, T

2001-07-01

Topical silicone gel sheeting has been used for more than 20 years to help reduce the size of hypertrophic scars and keloids. Its clinical efficacy and safety is well established. To determine whether topical silicone gel sheeting can be used to prevent hypertrophic scars and keloids from forming following dermatologic skin surgery. Patients undergoing skin surgery were stratified into two groups: those with no history of abnormal scarring (low-risk group) and those with a history of abnormal scarring (high-risk group). Following the procedure, patients within each group were randomized to receive either routine postoperative care or topical silicone gel sheeting (48 hours after surgery). Patients were followed for 6 months. In the low-risk group, there were no statistical differences between individuals using routine postoperative care or using topical silicone gel sheets. In the high-risk group, there was a statistical difference (39% versus 71%) between patients who did not develop abnormal scars and used topical silicone gel sheeting and patients who developed abnormal scars after routine postoperative treatment. Those individuals having a scar revision procedure also showed a statistical difference if topical silicone gel sheeting was used following surgery. Topical silicone gel sheeting, with a 20-year history of satisfaction in dermatology, now appears to be useful in the prevention of hypertrophic scars and keloids in patients undergoing scar revision.

Association of Kawasaki disease with tropospheric wind patterns.

PubMed

Rodó, Xavier; Ballester, Joan; Cayan, Dan; Melish, Marian E; Nakamura, Yoshikazu; Uehara, Ritei; Burns, Jane C

2011-01-01

The causal agent of Kawasaki disease (KD) remains unknown after more than 40 years of intensive research. The number of cases continues to rise in many parts of the world and KD is the most common cause of acquired heart disease in childhood in developed countries. Analyses of the three major KD epidemics in Japan, major non-epidemic interannual fluctuations of KD cases in Japan and San Diego, and the seasonal variation of KD in Japan, Hawaii, and San Diego, reveals a consistent pattern wherein KD cases are often linked to large-scale wind currents originating in central Asia and traversing the north Pacific. Results suggest that the environmental trigger for KD could be wind-borne. Efforts to isolate the causative agent of KD should focus on the microbiology of aerosols.

Association of Kawasaki disease with tropospheric wind patterns

PubMed Central

Rodó, Xavier; Ballester, Joan; Cayan, Dan; Melish, Marian E.; Nakamura, Yoshikazu; Uehara, Ritei; Burns, Jane C.

2011-01-01

The causal agent of Kawasaki disease (KD) remains unknown after more than 40 years of intensive research. The number of cases continues to rise in many parts of the world and KD is the most common cause of acquired heart disease in childhood in developed countries. Analyses of the three major KD epidemics in Japan, major non-epidemic interannual fluctuations of KD cases in Japan and San Diego, and the seasonal variation of KD in Japan, Hawaii, and San Diego, reveals a consistent pattern wherein KD cases are often linked to large-scale wind currents originating in central Asia and traversing the north Pacific. Results suggest that the environmental trigger for KD could be wind-borne. Efforts to isolate the causative agent of KD should focus on the microbiology of aerosols. PMID:22355668

The association between individual counselling and health behaviour change: the See Kidney Disease (SeeKD) targeted screening programme for chronic kidney disease.

PubMed

Galbraith, Lauren; Hemmelgarn, Brenda; Manns, Braden; Samuel, Susan; Kappel, Joanne; Valk, Nadine; Ronksley, Paul

2016-01-01

Health behaviour change is an important component of management for patients with chronic kidney disease (CKD); however, the optimal method to promote health behaviour change for self-management of CKD is unknown. The See Kidney Disease (SeeKD) targeted screening programme screened Canadians at risk for CKD and promoted health behaviour change through individual counselling and goal setting. The objectives of this study are to determine the effectiveness of individual counselling sessions for eliciting behaviour change and to describe participant characteristics associated with behaviour change. This is a cross-sectional, descriptive study. The study setting is the National SeeKD targeted screening programme. The participants are all 'at risk' patients who were screened for CKD and returned a follow-up health behaviour survey (n = 1129). Health behaviour change was defined as a self-reported change in lifestyle, including dietary changes or medication adherence. An individual counselling session was provided to participants by allied healthcare professionals to promote health behaviour change. A survey was mailed to all participants at risk of CKD within 2-4 weeks following the screening event to determine if behaviour changes had been initiated. Descriptive statistics were used to describe respondent characteristics and self-reported behaviour change following screening events. Results were stratified by estimated glomerular filtration rate (eGFR) (< 60 and ≥ 60 mL/min/1.73 m(2)). Log binomial regression analysis was used to determine the predictors of behaviour change. Of the 1129 respondents, the majority (89.8 %) reported making a health behaviour change after the screening event. Respondents who were overweight (body mass index [BMI] 25-29.9 kg/m(2)) or obese (BMI ≥ 30.0 kg/m(2)) were more likely to report a behaviour change (prevalence rate ratio (PRR) 0.66, 95 % confidence interval (CI) 0.44-0.99 and PRR 0.49, 95 % CI 0

Distribution coefficients (Kd's) for use in risk assessment models of the Kara Sea.

PubMed

Carroll, J; Boisson, F; Teyssie, J L; King, S E; Krosshavn, M; Carroll, M L; Fowler, S W; Povinec, P P; Baxter, M S

1999-07-01

As a prerequisite for most evaluations of radionuclide transport pathways in marine systems, it is necessary to obtain basic information on the sorption potential of contaminants onto particulate matter. Kd values for use in modeling radionuclide dispersion in the Kara Sea have been determined as part of several international programs addressing the problem of radioactive debris residing in Arctic Seas. Field and laboratory Kd experiments were conducted for the following radionuclides associated with nuclear waste: americium, europium, plutonium, cobalt, cesium and strontium. Emphasis has been placed on two regions in the Kara Sea: (i) the Novaya Zemlya Trough (NZT) and (ii) the mixing zones of the Ob and Yenisey Rivers (RMZ). Short-term batch Kd experiments were performed at-sea on ambient water column samples and on samples prepared both at-sea and in the laboratory by mixing filtered bottom water with small amounts of surficial bottom sediments (particle concentrations in samples = 1-30 mg/l). Within both regions, Kd values for individual radionuclides vary over two to three orders of magnitude. The relative particle affinities for radionuclides in the two regions are americium approximately equal to europium > plutonium > cobalt > cesium > strontium. The values determined in this study agree with minimum values given in the IAEA Technical Report [IAEA, 1985. Sediment Kd's and Concentration Factors for Radionuclides in the Marine Environment. Technical Report No. 247. International Atomic Energy Agency, Vienna.]. Given the importance of Kd's in assessments of critical transport pathways for radionuclide contaminants, we recommend that Kd ranges of values for specific elements rather than single mean values be incorporated into model simulations of radionuclide dispersion.

Lie Symmetry Analysis and Explicit Solutions of the Time Fractional Fifth-Order KdV Equation

PubMed Central

Wang, Gang wei; Xu, Tian zhou; Feng, Tao

2014-01-01

In this paper, using the Lie group analysis method, we study the invariance properties of the time fractional fifth-order KdV equation. A systematic research to derive Lie point symmetries to time fractional fifth-order KdV equation is performed. In the sense of point symmetry, all of the vector fields and the symmetry reductions of the fractional fifth-order KdV equation are obtained. At last, by virtue of the sub-equation method, some exact solutions to the fractional fifth-order KdV equation are provided. PMID:24523885

New analytical exact solutions of time fractional KdV-KZK equation by Kudryashov methods

NASA Astrophysics Data System (ADS)

S Saha, Ray

2016-04-01

In this paper, new exact solutions of the time fractional KdV-Khokhlov-Zabolotskaya-Kuznetsov (KdV-KZK) equation are obtained by the classical Kudryashov method and modified Kudryashov method respectively. For this purpose, the modified Riemann-Liouville derivative is used to convert the nonlinear time fractional KdV-KZK equation into the nonlinear ordinary differential equation. In the present analysis, the classical Kudryashov method and modified Kudryashov method are both used successively to compute the analytical solutions of the time fractional KdV-KZK equation. As a result, new exact solutions involving the symmetrical Fibonacci function, hyperbolic function and exponential function are obtained for the first time. The methods under consideration are reliable and efficient, and can be used as an alternative to establish new exact solutions of different types of fractional differential equations arising from mathematical physics. The obtained results are exhibited graphically in order to demonstrate the efficiencies and applicabilities of these proposed methods of solving the nonlinear time fractional KdV-KZK equation.

Evaluation of genistein ability to modulate CTGF mRNA/protein expression, genes expression of TGFβ isoforms and expression of selected genes regulating cell cycle in keloid fibroblasts in vitro.

PubMed

Jurzak, Magdalena; Adamczyk, Katarzyna; Antończak, Paweł; Garncarczyk, Agnieszka; Kuśmierz, Dariusz; Latocha, Małgorzata

2014-01-01

Keloids are characterized by overgrowth of connective tissue in the skin that arises as a consequence of abnormal wound healing. Normal wound healing is regulated by a complex set of interactions within a network of profibrotic and antifibrotic cytokines that regulate new extracellular matrix (ECM) synthesis and remodeling. These proteins include transforming growth factor β (TGFβ) isoforms and connective tissue growth factor (CTGF). TGFβ1 stimulates fibroblasts to synthesize and contract ECM and acts as a central mediator of profibrotic response. CTGF is induced by TGFβ1 and is considered a downstream mediator of TGFβ1action in fibroblasts. CTGF plays a crucial role in keloid pathogenesis by promoting prolonged collagen synthesis and deposition and as a consequence sustained fibrotic response. During keloids formation, besides imbalanced ECM synthesis and degradation, fibroblast proliferation and it's resistance to apoptosis is observed. Key genes that may play a role in keloid formation and growth involve: suppressor gene p53.,cyclin-depend- ent kinase inhibitor CDKN1A (p21) and BCL2 family genes: antiapoptotic BCL-2 and proapoptotic BAX. Genistein (4',5,7-trihydroxyisoflavone) exhibits multidirectional biological action. The concentration of genistein is relatively high in soybean. Genistein has been shown as effective antioxidant and chemopreventive agent. Genistein can bind to estrogen receptors (ERs) and modulate estrogen action due to its structure similarity to human estrogens. Genistein also inhibits transcription factors NFκB. Akt and AP-l signaling pathways, that are important for cytokines expression and cell proliferation, differentiation, survival and apoptosis. The aim of the study was to investigate genistein as a potential inhibitor of CTGF and TGFβ1, β2 and β3 isoforms expression and a potential regulator of p53. CDKN1A(p21), BAX and BCL-2 expression in normal fibroblasts and fibroblasts derived from keloids cultured in vitro. Real time

Use of synthetic peptide libraries for the H-2Kd binding motif identification.

PubMed

Quesnel, A; Casrouge, A; Kourilsky, P; Abastado, J P; Trudelle, Y

1995-01-01

To identify Kd-binding peptides, an approach based on small peptide libraries has been developed. These peptide libraries correspond to all possible single-amino acid variants of a particular Kd-binding peptide, SYIPSAEYI, an analog of the Plasmodium berghei 252-260 antigenic peptide SYIPSAEKI. In the parent sequence, each position is replaced by all the genetically encoded amino acids (except cysteine). The multiple analog syntheses are performed either by the Divide Couple and Recombine method or by the Single Resin method and generate mixtures containing 19 peptides. The present report deals with the synthesis, the purification, the chemical characterization by amino acid analysis and electrospray mass spectrometry (ES-MS), and the application of such mixtures in binding tests with a soluble, functionally empty, single-chain H-2Kd molecule denoted SC-Kd. For each mixture, bound peptides were eluted and analyzed by sequencing. Since the binding tests were realized in noncompetitive conditions, our results show that a much broader set of peptides bind to Kd than expected from previous studies. This may be of practical importance when looking for low affinity peptides such as tumor peptides capable of eliciting protective immune response.

Kawasaki disease and ENSO-driven wind circulation

NASA Astrophysics Data System (ADS)

Ballester, Joan; Burns, Jane C.; Cayan, Dan; Nakamura, Yosikazu; Uehara, Ritei; Rodó, Xavier

2013-05-01

disease (KD) is the most common cause of acquired heart disease in children worldwide. Recently, a climatological study suggested that KD may be triggered by a windborne agent traveling across the north Pacific through the westerly wind flow prevailing at midlatitudes. Here we use KD records to describe the association between enhanced disease activity on opposite sides of the basin and different phases of the El Niño-Southern Oscillation (ENSO) phenomenon, via the linkage to these tropospheric winds. Results show that years with higher-than-normal KD cases in Japan preferentially occur during either El Niño Modoki or La Niña conditions, while in San Diego during the mature phase of El Niño or La Niña events. Given that ENSO offers a degree of predictability at lead times of 6 months, these modulations suggest that seasonal predictions of KD could be used to alert clinicians to periods of increased disease activity.

A method for estimating the diffuse attenuation coefficient (KdPAR)from paired temperature sensors

USGS Publications Warehouse

Read, Jordan S.; Rose, Kevin C.; Winslow, Luke A.; Read, Emily K.

2015-01-01

A new method for estimating the diffuse attenuation coefficient for photosynthetically active radiation (KdPAR) from paired temperature sensors was derived. We show that during cases where the attenuation of penetrating shortwave solar radiation is the dominant source of temperature changes, time series measurements of water temperatures at multiple depths (z1 and z2) are related to one another by a linear scaling factor (a). KdPAR can then be estimated by the simple equation KdPAR ln(a)/(z2/z1). A suggested workflow is presented that outlines procedures for calculating KdPAR according to this paired temperature sensor (PTS) method. This method is best suited for conditions when radiative temperature gains are large relative to physical noise. These conditions occur frequently on water bodies with low wind and/or high KdPARs but can be used for other types of lakes during time periods of low wind and/or where spatially redundant measurements of temperatures are available. The optimal vertical placement of temperature sensors according to a priori knowledge of KdPAR is also described. This information can be used to inform the design of future sensor deployments using the PTS method or for campaigns where characterizing sub-daily changes in temperatures is important. The PTS method provides a novel method to characterize light attenuation in aquatic ecosystems without expensive radiometric equipment or the user subjectivity inherent in Secchi depth measurements. This method also can enable the estimation of KdPAR at higher frequencies than many manual monitoring programs allow.

Combined effects of long-pulsed neodymium-yttrium-aluminum-garnet laser, diprospan and 5-fluorouracil in the treatment of keloid scars.

PubMed

Chen, Xiao-E; Liu, Juan; Bin Jameel, Afzaal Ahmed; Valeska, Maya; Zhang, Jia-An; Xu, Yang; Liu, Xing-Wu; Zhou, Hong; Luo, Dan; Zhou, Bing-Rong

2017-06-01

Keloids are benign tumors that originate from scar tissues, but they usually overgrow beyond the original wounds. In a three-month single-center clinical trial, 69 patients were randomly divided into three groups. Patients in group 1 were treated with intralesional injection of diprospan (2 mg betamethasone disodium phosphate and 5 mg betamethasone dipropionate in 1 ml) with one-month intervals for three months. Patients in groups 2 and 3 were injected with a combination of 0.5 ml 5-fluorouracil (5-FU; 25 mg/ml) and diprospan as above for three months also. Prior to each injection, the keloids of patients in group 3 were additionally irradiated by a 1,064-nm neodymium-yttrium-aluminum-garnet (Nd:YAG) laser with a single pulse at an energy density of 90-100 J/cm 2 and a pulse width of 12 msec. Clinical responses were evaluated by patient self-assessment and overall assessment by an observer according to the clinical signs of erythema, pruritus and pliability. A total of sixty-two patients completed the tests of the present study. At 2 and 3 months, the patients in all treatment groups showed an acceptable improvement in nearly all measurements. At the end of the study, the erythema and toughness score was significantly reduced and itch reduction was significantly greater in the diprospan + 5-FU + Nd:YAG group when compared to those in the other groups (P<0.05 for all indexes). The acceptable responses (good to excellent improvements) reported by blinded observers were as follows: 12% in the diprospan group, 48% in the diprospan + 5-FU group and 69% in the diprospan + 5-FU + Nd:YAG group. All of the results indicated that the combination of diprospan + 5-FU + Nd:YAG was the most efficacious therapy for keloid scars.

Combined effects of long-pulsed neodymium-yttrium-aluminum-garnet laser, diprospan and 5-fluorouracil in the treatment of keloid scars

PubMed Central

Chen, Xiao-E; Liu, Juan; Bin Jameel, Afzaal Ahmed; Valeska, Maya; Zhang, Jia-An; Xu, Yang; Liu, Xing-Wu; Zhou, Hong; Luo, Dan; Zhou, Bing-Rong

2017-01-01

Keloids are benign tumors that originate from scar tissues, but they usually overgrow beyond the original wounds. In a three-month single-center clinical trial, 69 patients were randomly divided into three groups. Patients in group 1 were treated with intralesional injection of diprospan (2 mg betamethasone disodium phosphate and 5 mg betamethasone dipropionate in 1 ml) with one-month intervals for three months. Patients in groups 2 and 3 were injected with a combination of 0.5 ml 5-fluorouracil (5-FU; 25 mg/ml) and diprospan as above for three months also. Prior to each injection, the keloids of patients in group 3 were additionally irradiated by a 1,064-nm neodymium-yttrium-aluminum-garnet (Nd:YAG) laser with a single pulse at an energy density of 90–100 J/cm2 and a pulse width of 12 msec. Clinical responses were evaluated by patient self-assessment and overall assessment by an observer according to the clinical signs of erythema, pruritus and pliability. A total of sixty-two patients completed the tests of the present study. At 2 and 3 months, the patients in all treatment groups showed an acceptable improvement in nearly all measurements. At the end of the study, the erythema and toughness score was significantly reduced and itch reduction was significantly greater in the diprospan + 5-FU + Nd:YAG group when compared to those in the other groups (P<0.05 for all indexes). The acceptable responses (good to excellent improvements) reported by blinded observers were as follows: 12% in the diprospan group, 48% in the diprospan + 5-FU group and 69% in the diprospan + 5-FU + Nd:YAG group. All of the results indicated that the combination of diprospan + 5-FU + Nd:YAG was the most efficacious therapy for keloid scars. PMID:28588688

Efficacy of IPL device combined with intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with regards to the recovery of skin barrier function: A pilot study.

PubMed

Kim, Dong Young; Park, Hyun Sun; Yoon, Hyun-Sun; Cho, Soyun

2015-10-01

Keloids and hypertrophic scars are prevalent and psychologically distressful dermatologic conditions. Various treatment modalities have been tried but without complete success by any one method. We evaluated the efficacy of a combination of intense pulsed light (IPL) device and intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with respect to the recovery of skin barrier function. Totally 52 Korean patients were treated by the combined treatment at 4-8-week intervals. Using digital photographs, changes in scar appearance were assessed with modified Vancouver Scar Scale (MVSS), physicians' global assessment (PGA) and patient's satisfaction score. In 12 patients, the stratum corneum (SC) barrier function was assessed by measuring transepidermal water loss (TEWL) and SC capacitance. Most scars demonstrated significant clinical improvement in MVSS, PGA and patient's satisfaction score after the combined therapy. A significant decrease of TEWL and elevation of SC capacitance were also documented after the treatment. The combination therapy (IPL + corticosteroid injection) not only improves the appearance of keloids and hypertrophic scars but also increases the recovery level of skin hydration status in terms of the skin barrier function.

15kD Granulysin for Monocyte Differentiation: A New Immunotherapeutic for Both in vivo and ex vivo Applications | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a method of enhancing immune response in patients by using 15 kD granulysin. Granulysin, a proinflammatory molecule, is broadly applicable for the treatment of several diseases.

Participant acceptability of exercise in kidney disease (PACE-KD): a feasibility study protocol in renal transplant recipients

PubMed Central

Bishop, Nicolette C; Billany, Roseanne; Smith, Alice C

2017-01-01

Introduction Cardiovascular disease (CVD) is a major cause of mortality in renal transplant recipients (RTRs). General population risk scores for CVD underestimate the risk in patients with chronic kidney disease (CKD) suggesting additional non-traditional factors. Renal transplant recipients also exhibit elevated inflammation and impaired immune function. Exercise has a positive impact on these factors in patients with CKD but there is a lack of rigorous research in RTRs, particularly surrounding the feasibility and acceptability of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) in this population. This study aims to explore the feasibility of three different supervised aerobic exercise programmes in RTRs to guide the design of future large-scale efficacy studies. Methods and analysis Renal transplant recipients will be randomised to HIIT A (16 min interval training with 4, 2 and 1 min intervals at 80%–90% of peak oxygen uptake (VO2 peak)), HIIT B (4×4 min interval training at 80%–90% VO2peak) or MICT (~40 min cycling at 50%–60% VO2peak) where they will undertake 24 supervised sessions (approximately thrice weekly over 8 weeks). Assessment visits will be at baseline, midtraining, immediate post-training and 3 months post-training. The study will evaluate the feasibility of recruitment, randomisation, retention, assessment procedures and the implementation of the interventions. A further qualitative sub-study QPACE-KD (Qualitative Participant Acceptability of Exercise in Kidney Disease) will explore patient experiences and perspectives through semistructured interviews and focus groups. Ethics and dissemination All required ethical and regulatory approvals have been obtained. Findings will be disseminated through conference presentations, public platforms and academic publications. Trial registration number Prospectively registered; ISRCTN17122775. PMID:28947458

Participant acceptability of exercise in kidney disease (PACE-KD): a feasibility study protocol in renal transplant recipients.

PubMed

Bishop, Nicolette C; Billany, Roseanne; Smith, Alice C

2017-09-24

Cardiovascular disease (CVD) is a major cause of mortality in renal transplant recipients (RTRs). General population risk scores for CVD underestimate the risk in patients with chronic kidney disease (CKD) suggesting additional non-traditional factors. Renal transplant recipients also exhibit elevated inflammation and impaired immune function. Exercise has a positive impact on these factors in patients with CKD but there is a lack of rigorous research in RTRs, particularly surrounding the feasibility and acceptability of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) in this population. This study aims to explore the feasibility of three different supervised aerobic exercise programmes in RTRs to guide the design of future large-scale efficacy studies. Renal transplant recipients will be randomised to HIIT A (16 min interval training with 4, 2 and 1 min intervals at 80%-90% of peak oxygen uptake (VO 2 peak )), HIIT B (4×4 min interval training at 80%-90% VO 2peak ) or MICT (~40 min cycling at 50%-60% VO 2peak ) where they will undertake 24 supervised sessions (approximately thrice weekly over 8 weeks). Assessment visits will be at baseline, midtraining, immediate post-training and 3 months post-training. The study will evaluate the feasibility of recruitment, randomisation, retention, assessment procedures and the implementation of the interventions. A further qualitative sub-study QPACE-KD (Qualitative Participant Acceptability of Exercise in Kidney Disease) will explore patient experiences and perspectives through semistructured interviews and focus groups. All required ethical and regulatory approvals have been obtained. Findings will be disseminated through conference presentations, public platforms and academic publications. Prospectively registered; ISRCTN17122775. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is

Kawasaki Disease Increases the Incidence of Myopia.

PubMed

Kung, Yung-Jen; Wei, Chang-Ching; Chen, Liuh An; Chen, Jiin Yi; Chang, Ching-Yao; Lin, Chao-Jen; Lim, Yun-Ping; Tien, Peng-Tai; Chen, Hsuan-Ju; Huang, Yong-San; Lin, Hui-Ju; Wan, Lei

2017-01-01

The prevalence of myopia has rapidly increased in recent decades and has led to a considerable global public health concern. In this study, we elucidate the relationship between Kawasaki disease (KD) and the incidence of myopia. We used Taiwan's National Health Insurance Research Database to conduct a population-based cohort study. We identified patients diagnosed with KD and individuals without KD who were selected by frequency matched based on sex, age, and the index year. The Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence intervals for the comparison of the 2 cohorts. The log-rank test was used to test the incidence of myopia in the 2 cohorts. A total of 532 patients were included in the KD cohort and 2128 in the non-KD cohort. The risk of myopia (hazard ratio, 1.31; 95% confidence interval, 1.08-1.58; P < 0.01) was higher among patients with KD than among those in the non-KD cohort. The Cox proportional hazards regression model showed that irrespective of age, gender, and urbanization, Kawasaki disease was an independent risk factor for myopia. Patients with Kawasaki disease exhibited a substantially higher risk for developing myopia.

The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome II, and its polymorphisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, M.B.; Itoh, Kazuko; Fujisaku, Atsushi

1993-01-01

Autoantibodies to the ribonucleoprotein Ro/SSA occur in nearly half of the patients with systemic lupus erythematosus and are associated with lymphopenia, photosensitive dermatitis, and pulmonary and renal disease, which suggests that they have an immunopathologic role. The majority of Ro/SSA precipitin-positive patients produce serum antibodies that bind to the 60-kD and 52-kD Ro/SSA proteins. The authors previously isolated and determined the nucleotide sequence of a cDNA clone that encodes the 52-kD form of the human Ro/SSA protein. In the present study, they have determined the chromosomal location of the gene by in situ hybridization to the end of the shortmore » arm of chromosome 11. Hybridization of portions of the cDNA probe to restriction enzyme-digested DNA indicated the gene is composed of at least three exons. The exon encoding the putative zinc fingers of this protein was found to be distinct from that which encodes the leucine zipper. An RFLP of this gene was identified and is associated with the presence of lupus, primarily in black Americans. 60 refs., 3 figs., 3 tabs.« less

Can single use negative pressure wound therapy be an alternative method to manage keloid scarring? A preliminary report of a clinical and ultrasound/colour-power-doppler study.

PubMed

Fraccalvieri, Marco; Sarno, Antonino; Gasperini, Stefano; Zingarelli, Enrico; Fava, Raffaella; Salomone, Marco; Bruschi, Stefano

2013-06-01

Keloid scarring represents a pathological healing where primary healing phenomenon is deviated from normal. Pico is a single use negative pressure wound therapy system originally introduced to manage open or just closed wounds. Pico dressing is made of silicone, and distributes an 80 mmHg negative pressure across wound bed. Combination of silicon layer and continuous compression could be a valid method to manage keloid scarring. Since November 2011, three patients were enrolled and evaluated before negative pressure treatment, at end of treatment (1 month) and 2 months later, through Vancouver Scar Scale (VSS), Visual Analog Scale (VAS) and a scoring system for itching. Ultrasound (US) and colour-power-doppler (CPD) examination was performed to evaluate thickness and vascularisation of the scar. One patient was discharged from study after 1 week. In last two patients, VSS, VAS and itching significantly improved after 1 month therapy and the results were stable after 2 months without any therapy. At end of therapy, the 'appearance of palisade vessels' disappeared in both cases at CPD exam; US showed a thickness reduction (average 43·8%). We propose a well-tolerated, non invasive treatment to manage keloid scarring. Prospective studies are necessary to investigate whether these preliminary observations are confirmed. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Kawasaki disease in Sicily: clinical description and markers of disease severity.

PubMed

Maggio, Maria Cristina; Corsello, Giovanni; Prinzi, Eugenia; Cimaz, Rolando

2016-11-02

Kawasaki disease (KD) is an acute systemic vasculitis of small and middle size arteries; 15-25 % of untreated patients and 5 % of patients treated with intravenous immunoglobulin (IVIG) develop coronary artery lesions (CAL). Many studies tried to find the most effective treatment in the management of resistant KD and to select the risk factors for CAL. Our data are assessed on children from west Sicily, characterized by a genetic heterogeneity. We studied the clinical data of 70 KD Sicilian children (36 males: 51 %; 34 females: 49 %), analysed retrospectively, including: demographic and laboratory parameters; echocardiographic findings at diagnosis, at 2, 6 and 8 weeks, and at 1 year after the onset of the illness. Forty-seven had Typical KD, three Atypical KD and twenty Incomplete KD. Age at the disease onset ranged from 0.1 to 8.9 years. IVIG were administered 5 ± 2 days after the fever started. Defervescence occurred 39 ± 26 hours after the first IVIG infusion. Fifty-six patients (80 %) received 1 dose of IVIG (responders); 14 patients (20 %) had a resistant KD, with persistent fever after the first IVIG dose (non responders). Ten (14 %) non responders responded to the second dose, 4 (5 %) responded to three doses; one needed treatment with high doses of steroids and Infliximab. Cardiac involvement was documented in twenty-two cases (eighteen with transient dilatation/ectasia, fifteen with aneurysms). Pericardial effusion, documented in eleven, was associated with coronaritis and aneurysms, and was present earlier than coronary involvement in seven. Hypoalbuminemia, D-dimer pre-IVIG, gamma-GT pre-IVIG showed a statistically significant direct correlation with IVIG doses, highlighting the role of these parameters as predictor markers of refractory disease. The persistence of elevated CRP, AST, ALT levels, a persistent hyponatremia and hypoalbuminemia after IVIG therapy, also had a statistical significant correlation with IVIG doses. Non responders

Pathophysiologic insights into motor axonal function in Kennedy disease.

PubMed

Vucic, Steve; Kiernan, Matthew C

2007-11-06

Kennedy disease (KD), or spinobulbomuscular atrophy, is a slowly progressive inherited neurodegenerative disorder, marked by prominent fasciculations that typically precede the development of other symptoms. Although the genetic basis of KD relates to triplet (CAG) repeat expansion in the androgen receptor (AR) gene on the X chromosome, the mechanisms underlying the clinical presentation in KD have yet to be established. Consequently, the present study applied axonal excitability techniques to investigate the pathophysiologic mechanisms associated with KD. Peripheral nerve excitability studies were undertaken in 7 patients with KD with compound muscle action potentials (CMAP) recorded from the right abductor pollicis brevis. Strength-duration time constant (KD 0.54 +/- 0.03 msec; controls, 0.41 +/- 0.02 msec, p < 0.01) and the hyperpolarizing current/threshold gradient (KD 0.42 +/- 0.01; controls, 0.37 +/- 0.01, p < 0.05) were significantly increased in KD. Strength-duration time constant correlated with the CMAP amplitude (R = 0.68) and the fasciculation frequency (R = 0.62). Threshold electrotonus revealed greater changes in response to subthreshold depolarizing (KD TEd [90 to 100 msec], 50.75 +/- 1.98%; controls TEd [90 to 100 msec], 45.67 +/- 0.67%, p < 0.01) and hyperpolarizing (KD TEh [90 to 100 msec], 128.5 +/- 6.9%; controls TEh [90 to 100 msec], 120.5 +/- 2.4%) conditioning pulses. Measurements of refractoriness, superexcitability, and late subexcitability changed appropriately for axonal hyperpolarization, perhaps reflecting the effects of increased ectopic activity. In total, the increase in the strength-duration time constant may be the primary event, occurring early in course of the disease, contributing to the development of axonal hyperexcitability in Kennedy disease, and thereby to the generation of fasciculations, a characteristic hallmark of the disease.

Characterization of the protective capacity and immunogenicity of the 69-kD outer membrane protein of Bordetella pertussis

PubMed Central

1990-01-01

Immunization with the 69-kD outer membrane protein (OMP) of Bordetella pertussis protected neonatal mice against lethal respiratory challenge with B. pertussis 18323. Active immunization elicited a serum IgG anti- 69-kD OMP response at the time of challenge, with IgG anti-69-kD OMP antibodies detected in bronchoalveolar lavage fluid after challenge. Intravenous administration of BPE8, a monoclonal IgG1 anti-69-kD OMP, also protected young mice against B. pertussis challenge. Intravenously injected BPE8 was detected in the lungs of mice at the time of aerosol challenge, suggesting that the presence of specific antibody in the lungs may mediate protection. Thus the 69-kD OMP of B. pertussis is a protective antigen in mice that elicits specific serum antibody that can transude to the lung. The 69-kD OMP was detected in a preparation of a Takeda acellular vaccine by immunoblot analysis and a serum antibody response to the 69-kD OMP was observed in 18-mo-old children boosted with this preparation of Japanese acellular vaccine. Our results demonstrate that the B. pertussis 69-kD OMP is a protective antigen in animals, is immunogenic in humans, and is present in a preparation of acellular pertussis vaccine that is widely used in Japan. These findings indicate that the 69-kD OMP should be seriously considered as a candidate for inclusion in new formulations of antigenically defined acellular pertussis vaccines. PMID:2295882

Sociodemographic profile of children with Kawasaki disease in North India.

PubMed

Prakash, Jeya; Singh, Surjit; Gupta, Anju; Bharti, Bhavneet; Bhalla, A K

2016-03-01

Kawasaki disease (KD) is now the commonest cause of acquired heart disease in children in developed countries. KD occurs all over the world, including developing countries. The present study steps out to explore our hypothesis, driven by clinical observation over the last 18 years, whether children with KD in North India are of a higher socioeconomic status than children with other rheumatologic diseases. One hundred consecutive children with KD, registered in Pediatric Rheumatology Clinic before January 2011, were enrolled as cases. Children with other rheumatologic diseases were taken as controls. Assessment of socioeconomic status was done by administering the Aggarwal scale. Data were collected through interview. Statistical analysis was done using SPSS package version 16. On univariate analysis, male sex, higher educational status of parents, urban residence, immunization status being complete, and higher scores on Aggarwal scale were found to be significantly associated with KD. On multivariate analysis, only male sex and urban residence were found to be significantly associated with KD (p < 0.001). Families of children with KD tend to have a better sociodemographic profile when compared with other pediatric rheumatologic disorders in North India. These results, however, need to be replicated in a multicentric study for any firm conclusions to be drawn.

Establishment of Kawasaki disease database based on metadata standard.

PubMed

Park, Yu Rang; Kim, Jae-Jung; Yoon, Young Jo; Yoon, Young-Kwang; Koo, Ha Yeong; Hong, Young Mi; Jang, Gi Young; Shin, Soo-Yong; Lee, Jong-Keuk

2016-07-01

Kawasaki disease (KD) is a rare disease that occurs predominantly in infants and young children. To identify KD susceptibility genes and to develop a diagnostic test, a specific therapy, or prevention method, collecting KD patients' clinical and genomic data is one of the major issues. For this purpose, Kawasaki Disease Database (KDD) was developed based on the efforts of Korean Kawasaki Disease Genetics Consortium (KKDGC). KDD is a collection of 1292 clinical data and genomic samples of 1283 patients from 13 KKDGC-participating hospitals. Each sample contains the relevant clinical data, genomic DNA and plasma samples isolated from patients' blood, omics data and KD-associated genotype data. Clinical data was collected and saved using the common data elements based on the ISO/IEC 11179 metadata standard. Two genome-wide association study data of total 482 samples and whole exome sequencing data of 12 samples were also collected. In addition, KDD includes the rare cases of KD (16 cases with family history, 46 cases with recurrence, 119 cases with intravenous immunoglobulin non-responsiveness, and 52 cases with coronary artery aneurysm). As the first public database for KD, KDD can significantly facilitate KD studies. All data in KDD can be searchable and downloadable. KDD was implemented in PHP, MySQL and Apache, with all major browsers supported.Database URL: http://www.kawasakidisease.kr. © The Author(s) 2016. Published by Oxford University Press.

Management of Kawasaki disease

PubMed Central

Eleftheriou, D; Levin, M; Shingadia, D; Tulloh, R; Klein, NJ; Brogan, PA

2014-01-01

Kawasaki disease (KD) is an acute self-limiting inflammatory disorder, associated with vasculitis, affecting predominantly medium-sized arteries, particularly the coronary arteries. In developed countries KD is the commonest cause of acquired heart disease in childhood. The aetiology of KD remains unknown, and it is currently believed that one or more as yet unidentified infectious agents induce an intense inflammatory host response in genetically susceptible individuals. Genetic studies have identified several susceptibility genes for KD and its sequelae in different ethnic populations, including FCGR2A, CD40, ITPKC, FAM167A-BLK and CASP3, as well as genes influencing response to intravenous immunoglobulin (IVIG) and aneurysm formation such as FCGR3B, and transforming growth factor (TGF) β pathway genes. IVIG and aspirin are effective therapeutically, but recent clinical trials and meta-analyses have demonstrated that the addition of corticosteroids to IVIG is beneficial for the prevention of coronary artery aneurysms (CAA) in severe cases with highest risk of IVIG resistance. Outside of Japan, however, clinical scores to predict IVIG resistance perform suboptimally. Furthermore, the evidence base does not provide clear guidance on which corticosteroid regimen is most effective. Other therapies, including anti-TNFα, could also have a role for IVIG-resistant KD. Irrespective of these caveats, it is clear that therapy that reduces inflammation in acute KD, improves outcome. This paper summarises recent advances in the understanding of KD pathogenesis and therapeutics, and provides an approach for managing KD patients in the UK in the light of these advances. PMID:24162006

Cardiac Complications, Earlier Treatment, and Initial Disease Severity in Kawasaki Disease.

PubMed

Abrams, Joseph Y; Belay, Ermias D; Uehara, Ritei; Maddox, Ryan A; Schonberger, Lawrence B; Nakamura, Yosikazu

2017-09-01

To assess if observed higher observed risks of cardiac complications for patients with Kawasaki disease (KD) treated earlier may reflect bias due to confounding from initial disease severity, as opposed to any negative effect of earlier treatment. We used data from Japanese nationwide KD surveys from 1997 to 2004. Receipt of additional intravenous immunoglobulin (IVIG) (data available all years) or any additional treatment (available for 2003-2004) were assessed as proxies for initial disease severity. We determined associations between earlier or later IVIG treatment (defined as receipt of IVIG on days 1-4 vs days 5-10 of illness) and cardiac complications by stratifying by receipt of additional treatment or by using logistic modeling to control for the effect of receiving additional treatment. A total of 48 310 patients with KD were included in the analysis. In unadjusted analysis, earlier IVIG treatment was associated with a higher risk for 4 categories of cardiac complications, including all major cardiac complications (risk ratio, 1.10; 95% CI, 1.06-1.15). Stratifying by receipt of additional treatment removed this association, and earlier IVIG treatment became protective against all major cardiac complications when controlling for any additional treatment in logistic regressions (OR, 0.90; 95% CI, 0.80-1.00). Observed higher risks of cardiac complications among patients with KD receiving IVIG treatment on days 1-4 of the illness are most likely due to underlying higher initial disease severity, and patients with KD should continue to be treated with IVIG as early as possible. Published by Elsevier Inc.

Dissipative behavior of some fully non-linear KdV-type equations

NASA Astrophysics Data System (ADS)

Brenier, Yann; Levy, Doron

2000-03-01

The KdV equation can be considered as a special case of the general equation u t+f(u) x-δg(u xx) x=0, δ>0, where f is non-linear and g is linear, namely f( u)= u2/2 and g( v)= v. As the parameter δ tends to 0, the dispersive behavior of the KdV equation has been throughly investigated (see, e.g., [P.G. Drazin, Solitons, London Math. Soc. Lect. Note Ser. 85, Cambridge University Press, Cambridge, 1983; P.D. Lax, C.D. Levermore, The small dispersion limit of the Korteweg-de Vries equation, III, Commun. Pure Appl. Math. 36 (1983) 809-829; G.B. Whitham, Linear and Nonlinear Waves, Wiley/Interscience, New York, 1974] and the references therein). We show through numerical evidence that a completely different, dissipative behavior occurs when g is non-linear, namely when g is an even concave function such as g( v)=-∣ v∣ or g( v)=- v2. In particular, our numerical results hint that as δ→0 the solutions strongly converge to the unique entropy solution of the formal limit equation, in total contrast with the solutions of the KdV equation.

Suppressed plasmablast responses in febrile infants, including children with Kawasaki disease

PubMed Central

Martin, Meghan; Wrotniak, Brian H.

2018-01-01

Background Kawasaki disease (KD), the leading cause of acquired heart disease in children, primarily affects infants and toddlers. Investigations on immune responses during KD are hampered by a limited understanding of normal immune responses in these ages. It’s well known that Infants have poorer vaccine responses and difficulty with maintaining prolonged serum immunity, but there are few studies on human infants detailing immune deficiencies. Limited studies propose an inability to maintain life-long bone marrow plasma cells. Plasmablasts are a transitional cell form of B cells that lead to long-term Plasma cells. Plasmablasts levels rise in the peripheral blood after exposure to a foreign antigen. In adult studies, these responses are both temporally and functionally well characterized. To date, there have been few studies on plasmablasts in the predominant age range of KD. Methods Children presenting to an urban pediatric emergency room undergoing laboratory evaluation, who had concern of KD or had fever and symptoms overlapping those of KD, were recruited. Peripheral blood mononuclear cells were isolated and evaluated utilizing flow cytometry with specific B cell markers from 18 KD subjects and 69 febrile controls. Results Plasmablast numbers and temporal formation are similar between infectious disease controls and KD subjects. In both groups, infants have diminished plasmablast responses compared to older children. Conclusion In this single-time point survey, infants have a blunted peripheral plasmablast response. Overall, similar plasmablast responses in KD and controls support an infectious disease relationship to KD. Future time-course studies of plasmablasts in infants are warranted as this phenomenon may contribute to observed immune responses in this age group. PMID:29579044

Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells.

PubMed

Diep, Duy Trong Vien; Hong, Kyungki; Khun, Triyeng; Zheng, Mei; Ul-Haq, Asad; Jun, Hee-Sook; Kim, Young-Bum; Chun, Kwang-Hoon

2018-02-06

Adipose tissue is a specialized organ that synthesizes and stores fat. During adipogenesis, Rho and Rho-associated kinase (ROCK) 2 are inactivated, which enhances the expression of pro-adipogenic genes and induces the loss of actin stress fibers. Furthermore, pan ROCK inhibitors enhance adipogenesis in 3T3-L1 cells. Here, we show that KD025 (formerly known as SLx-2119), a ROCK2-specific inhibitor, suppresses adipogenesis in 3T3-L1 cells partially through a ROCK2-independent mechanism. KD025 downregulated the expression of key adipogenic transcription factors PPARγ and C/EBPα during adipogenesis in addition to lipogenic factors FABP4 and Glut4. Interestingly, adipogenesis was blocked by KD025 during days 1~3 of differentiation; after differentiation terminated, lipid accumulation was unaffected. Clonal expansion occurred normally in KD025-treated cells. These results suggest that KD025 could function during the intermediate stage after clonal expansion. Data from depletion of ROCKs showed that KD025 suppressed cell differentiation partially independent of ROCK's activity. Furthermore, no further loss of actin stress fibers emerged in KD025-treated cells during and after differentiation compared to control cells. These results indicate that in contrast to the pro-adipogenic effect of pan-inhibitors, KD025 suppresses adipogenesis in 3T3-L1 cells by regulating key pro-adipogenic factors. This outcome further implies that KD025 could be a potential anti-adipogenic/obesity agent.

Diagnosis of systemic-onset juvenile idiopathic arthritis after treatment for presumed Kawasaki disease.

PubMed

Dong, Siwen; Bout-Tabaku, Sharon; Texter, Karen; Jaggi, Preeti

2015-05-01

To estimate the incidence of systemic-onset juvenile idiopathic arthritis (SoJIA) within 6 months after treatment for presumed Kawasaki disease (KD) (presumed patients with KD with subsequent diagnosis of SoJIA [pKD/SoJIA]) and describe presentation differences from sole KD. We identified patients treated for KD at Nationwide Children's Hospital and from the Pediatric Health Information System from 2009-2013. We then identified the subset of children, pKD/SoJIA, who received an International Classification of Diseases, Ninth Revision code for SoJIA and had it listed at least once 3 months after and within 6 months after KD diagnosis. Demographic characteristics, readmission rates, treatments, and complications were noted. A literature review was also performed to identify clinical, laboratory, and echocardiographic data of previously documented patients with KD later diagnosed with SoJIA. There were 6745 total treated patients with KD in the Pediatric Health Information System database during the study period; 10 patients were identified to have pKD/SoJIA (0.2% of cohort). Those with pKD/SoJIA were predominantly Caucasian compared with patients with KD (90% and 46.8%, respectively; P=.003). Macrophage activation syndrome was more common in patients with pKD/SoJIA than in sole patients with KD (30% and 0.30%, respectively; P<.001). Fifteen cases of pKD/SoJIA were identified by literature and chart review, 12 of whom were initially diagnosed with incomplete KD. We reported a 0.2% incidence of pKD/SoJIA, which was associated with Caucasian race, macrophage activation syndrome, and an incomplete KD phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

Exact Solutions, Symmetry Reductions, Painlevé Test and Bäcklund Transformations of A Coupled KdV Equation

NASA Astrophysics Data System (ADS)

Min-Hui, XU; Man, JIA

2017-10-01

A coupled KdV equation is studied in this manuscript. The exact solutions, such as the periodic wave solutions and solitary wave solutions by means of the deformation and mapping approach from the solutions of the nonlinear ϕ 4 model are given. Using the symmetry theory, the Lie point symmetries and symmetry reductions of the coupled KdV equation are presented. The results show that the coupled KdV equation possesses infinitely many symmetries and may be considered as an integrable system. Also, the Painlevé test shows the coupled KdV equation possesses Painlevé property. The Bäcklund transformations of the coupled KdV equation related to Painlevé property and residual symmetry are shown. Supported by the National Natural Science Foundation of China under Grant Nos. 11675084 and 11435005, Ningbo Natural Science Foundation under Grant No. 2015A610159 and granted by the Opening Project of Zhejiang Provincial Top Key Discipline of Physics Sciences in Ningbo University under Grant No. xkzwl1502, and the authors are sponsored by K. C. Wong Magna Fund in Ningbo University

The 193-Kd Vault Protein, Vparp, Is a Novel Poly(Adp-Ribose) Polymerase

PubMed Central

Kickhoefer, Valerie A.; Siva, Amara C.; Kedersha, Nancy L.; Inman, Elisabeth M.; Ruland, Cristina; Streuli, Michel; Rome, Leonard H.

1999-01-01

Mammalian vaults are ribonucleoprotein (RNP) complexes, composed of a small ribonucleic acid and three proteins of 100, 193, and 240 kD in size. The 100-kD major vault protein (MVP) accounts for >70% of the particle mass. We have identified the 193-kD vault protein by its interaction with the MVP in a yeast two-hybrid screen and confirmed its identity by peptide sequence analysis. Analysis of the protein sequence revealed a region of ∼350 amino acids that shares 28% identity with the catalytic domain of poly(ADP-ribose) polymerase (PARP). PARP is a nuclear protein that catalyzes the formation of ADP-ribose polymers in response to DNA damage. The catalytic domain of p193 was expressed and purified from bacterial extracts. Like PARP, this domain is capable of catalyzing a poly(ADP-ribosyl)ation reaction; thus, the 193-kD protein is a new PARP. Purified vaults also contain the poly(ADP-ribosyl)ation activity, indicating that the assembled particle retains enzymatic activity. Furthermore, we show that one substrate for this vault-associated PARP activity is the MVP. Immunofluorescence and biochemical data reveal that p193 protein is not entirely associated with the vault particle, suggesting that it may interact with other protein(s). A portion of p193 is nuclear and localizes to the mitotic spindle. PMID:10477748

Localization of the human 64kD autoantigen D1 to myofibrils in a subset of extraocular muscle fibers

NASA Technical Reports Server (NTRS)

Conley, C. A.; Fowler, V. M.

1999-01-01

PURPOSE. To evaluate the tissue-specific expression pattern of the 64kD human autoantigen D1, a tropomodulin-related protein that may be involved in thyroid-associated ophthalmopathy. METHODS. Recombinant 64kD human autoantigen D1 was generated in a bacterial expression system and used to immunize rabbits. Specific antibodies were affinity-purified and used for Western blots on normal and hyperthyroid rat and rabbit tissue, and immunofluorescence localization on cryosections of rat tissue. RESULTS. Anti-64kD human autoantigen D1 antibodies recognize specifically a approximately 70kD polypeptide in western blots of extraocular muscle, sternothyroid muscle, and smooth muscle. Immunofluorescence staining demonstrates that the 64kD human autoantigen D1 localizes to myofibrils in slow fibers from rat extraocular and sternothyroid muscle. The level of this protein is not altered in extraocular muscles from hyperthyroid rabbits. CONCLUSIONS. The 64kD human autoantigen D1 is expressed in slow fibers of extraocular and sternothyroid muscles as a component of myofibrils, and is not upregulated in conditions of hyperthyroidism.

Lasers and ancillary treatments for scar management Part 2: Keloid, hypertrophic, pigmented and acne scars

PubMed Central

McGoldrick, Rory Boyd; Theodorakopoulou, Evgenia; Azzopardi, Ernest Anthony; Murison, Maxwell

2017-01-01

The formation of a wide range of excessive scars following various skin injuries is a natural consequence of healing. Scars resulting from surgery or trauma affect approximately 100 million people per annum in the developed world and can have profound physical, aesthetic, psychological and social consequences. Thus, scar treatment is a priority for patient and physician alike. Laser treatment plays an important role in scar management with additional support from ancillary modalities. Subsequent to part 1: Burns scars, part 2 focuses on our strategies and literature review of treatment of keloid, hypertrophic, pigmented and acne scars where lasers are used in conjunction with other measures, and illustrated with case studies. PMID:29799579

Amyloid Precursor-like Protein 2 Increases the Endocytosis, Instability, and Turnover of the H2-Kd MHC Class I Molecule1

PubMed Central

Tuli, Amit; Sharma, Mahak; McIlhaney, Mary M.; Talmadge, James E.; Naslavsky, Naava; Caplan, Steve; Solheim, Joyce C.

2008-01-01

The defense against the invasion of viruses and tumors relies on the presentation of viral and tumor-derived peptides to cytotoxic T lymphocytes by cell surface major histocompatibility complex (MHC) class I molecules. Previously, we showed that the ubiquitously expressed protein amyloid precursor-like protein 2 (APLP2) associates with the folded form of the MHC class I molecule Kd. In the current study, APLP2 was found to associate with folded Kd molecules following their endocytosis and to increase the amount of endocytosed Kd. In addition, increased expression of APLP2 was shown to decrease Kd surface expression and thermostability. Correspondingly, Kd thermostability and surface expression were increased by down-regulation of APLP2 expression. Overall, these data suggest that APLP2 modulates the stability and endocytosis of Kd molecules. PMID:18641335

The University Münster Model Surgery System for Orthognathic Surgery. Part II -- KD-MMS.

PubMed

Ehmer, Ulrike; Joos, Ulrich; Ziebura, Thomas; Flieger, Stefanie; Wiechmann, Dirk

2013-01-04

Model surgery is an integral part of the planning procedure in orthognathic surgery. Most concepts comprise cutting the dental cast off its socket. The standardized spacer plates of the KD-MMS provide for a non-destructive, reversible and reproducible means of maxillary and/or mandibular plaster cast separation. In the course of development of the system various articulator types were evaluated with regard to their capability to provide a means of realizing the concepts comprised of the KD-MMS. Special attention was dedicated to the ability to perform three-dimensional displacements without cutting of plaster casts. Various utilities were developed to facilitate maxillary displacement in accordance to the planning. Objectives of this development comprised the ability to implement the values established in the course of two-dimensional ceph planning. The system - KD-MMS comprises a set of hardware components as well as a defined procedure. Essential hardware components are red spacer and blue mounting plates. The blue mounting plates replace the standard yellow SAM mounting elements. The red spacers provide for a defined leeway of 8 mm for three-dimensional movements. The non-destructive approach of the KD-MMS makes it possible to conduct different model surgeries with the same plaster casts as well as to restore the initial, pre-surgical situation at any time. Thereby, surgical protocol generation and gnathologic splint construction are facilitated. The KD-MMS hardware components in conjunction with the defined procedures are capable of increasing efficiency and accuracy of model surgery and splint construction. In cases where different surgical approaches need to be evaluated in the course of model surgery, a significant reduction of chair time may be achieved.

Numerical simulation of KdV equation by finite difference method

NASA Astrophysics Data System (ADS)

Yokus, A.; Bulut, H.

2018-05-01

In this study, the numerical solutions to the KdV equation with dual power nonlinearity by using the finite difference method are obtained. Discretize equation is presented in the form of finite difference operators. The numerical solutions are secured via the analytical solution to the KdV equation with dual power nonlinearity which is present in the literature. Through the Fourier-Von Neumann technique and linear stable, we have seen that the FDM is stable. Accuracy of the method is analyzed via the L2 and L_{∞} norm errors. The numerical, exact approximations and absolute error are presented in tables. We compare the numerical solutions with the exact solutions and this comparison is supported with the graphic plots. Under the choice of suitable values of parameters, the 2D and 3D surfaces for the used analytical solution are plotted.

Septated pericarditis associated with Kawasaki disease: a brief case report.

PubMed

Sonçaği, Arzu; Devrim, Ilker; Karagöz, Tevfik; Dilber, Embiya; Celiker, Alpay; Ozen, Seza; Seçmeer, Gülten

2007-01-01

Kawasaki disease (KD) is primarily the systemic vasculitis of childhood that affects mainly the medium-sized arteries, such as the coronary arteries. KD is the leading cause of acquired heart disease, whereas the incidence of rheumatic fever has declined. The most serious complication is coronary artery involvement. Among the children with KD who developed cardiac complications, pericarditis is a rare complication, with an incidence of 0.07%. We report our experience in a 5.5-year-old child with KD complicated with aneurysm of the left anterior descendant coronary artery and septated pericardial effusion, which has not been reported in the literature. The pericardial effusion disappeared very dramatically with intravenous immunoglobulin (IVIG) therapy. We would like to point out that septated pericardial effusion in cases of KD do not need any further therapy other than IVIG and high-dose acetylsalicylic acid.

The 14.6 kd rubber elongation factor (Hev b 1) and 24 kd (Hev b 3) rubber particle proteins are recognized by IgE from patients with spina bifida and latex allergy.

PubMed

Yeang, H Y; Cheong, K F; Sunderasan, E; Hamzah, S; Chew, N P; Hamid, S; Hamilton, R G; Cardosa, M J

1996-09-01

Two major water-insoluble proteins are located on the surface of rubber particles in Hevea brasiliensis latex. A 14.6 kd protein (Hev b 1), found mainly on large rubber particles (> 350 mm in diameter), and a 24 kd protein (Hev b 3), found mainly on small rubber particles (average diameter, 70 nm), are recognized by IgE from patients with spina bifida and latex allergy. Although Hev b 1 (also called the rubber elongation factor [REF]) has previously been reported as a major latex allergen, this conclusion has been disputed on the basis of results from other studies. The allergenicity of Hev b 1 is verified in this study by testing the recombinant protein generated from its gene. Because allergenicity is confined to patients with spina bifida and not observed in adults sensitive to latex, it is not a major latex allergen. The identification of Hev b 3 as another allergen originating from rubber particles is confirmed by immunogold labeling and electron microscopy. Observations with the monoclonal antibody USM/RC2 developed against Hev b 3 show that the protein has a tendency to fragment into several polypeptides of lower molecular weight (from 24 kd to about 5 kd) when stored at -20 degrees C. There is also indication of protein aggregation from the appearance of proteins with molecular weights greater than 24 kd. Fragmentation of Hev b 3 is induced immediately on he addition of latex B-serum, which is normally compartmentalized in the lutoids in fresh latex. In the preparation of ammoniated latex (used for the manufacture of latex products), the lutoids are ruptured, and the released B-serum reacts with Hev b 3 on the rubber particles to give rise to an array of low molecular weight polypeptides that are allergenic to patients with spina bifida.

Modified KdV equation for trapped ions in polarized dusty plasma

NASA Astrophysics Data System (ADS)

Singh, K.; Kaur, N.; Sethi, P.; Saini, N. S.

2018-01-01

In this investigation, the effect of polarization force on dust acoustic solitary waves (DASWs) has been presented in a dusty plasma composed of Maxwellian electrons, vortex-like (trapped) ions, and negatively charged mobile dust grains. It has been found that from the Maxwellian ions distribution to a vortex-like one, the dynamics of small but finite amplitude DA solitary waves is governed by a nonlinear equation of modified Korteweg-de Vries (mKdV) type instead of KdV. The combined effect of trapped ions and polarization force strongly influence the characteristics of DASWs. Only rarefactive solitary structures are formed under the influence of ions trapping and polarization force. The implications of our results are useful in real astrophysical situations of space and laboratory dusty plasmas.

Newborn Screening for Krabbe’s Disease

PubMed Central

Orsini, Joseph J.; Saavedra-Matiz, Carlos A.; Gelb, Michael H.; Caggana, Michele

2017-01-01

Live newborn screening for Krabbe’s disease (KD) was initiated in New York on August 7, 2006, and started in Missouri in August, 2012. As of August 7, 2015, nearly 2.5 million infants had been screened, and 443 (0.018%) infants had been referred for followup clinical evaluation; only five infants had been determined to have KD. As of August, 2015, the combined incidence of infantile KD in New York and Missouri is ~1 per 500,000; however, patients who develop later-onset forms of KD may still emerge. This Review provides an overview of the processes used to develop the screening and followup algorithms. It also includes updated results from screening and discussion of observations, lessons learned, and suggested areas for improvement that will reduce referral rates and the number of infants defined as at risk for later-onset forms of KD. Although current treatment options for infants with early-infantile Krabbe’s disease are not curative, over time treatment options should improve; in the meantime, it is essential to evaluate the lessons learned and to ensure that screening is completed in the best possible manner until these improvements can be realized. PMID:27638592

Comparison of in situ uranium KD values with a laboratory determined surface complexation model

USGS Publications Warehouse

Curtis, G.P.; Fox, P.; Kohler, M.; Davis, J.A.

2004-01-01

Reactive solute transport simulations in groundwater require a large number of parameters to describe hydrologic and chemical reaction processes. Appropriate methods for determining chemical reaction parameters required for reactive solute transport simulations are still under investigation. This work compares U(VI) distribution coefficients (i.e. KD values) measured under field conditions with KD values calculated from a surface complexation model developed in the laboratory. Field studies were conducted in an alluvial aquifer at a former U mill tailings site near the town of Naturita, CO, USA, by suspending approximately 10 g samples of Naturita aquifer background sediments (NABS) in 17-5.1-cm diameter wells for periods of 3 to 15 months. Adsorbed U(VI) on these samples was determined by extraction with a pH 9.45 NaHCO3/Na2CO3 solution. In wells where the chemical conditions in groundwater were nearly constant, adsorbed U concentrations for samples taken after 3 months of exposure to groundwater were indistinguishable from samples taken after 15 months. Measured in situ K D values calculated from the measurements of adsorbed and dissolved U(VI) ranged from 0.50 to 10.6 mL/g and the KD values decreased with increasing groundwater alkalinity, consistent with increased formation of soluble U(VI)-carbonate complexes at higher alkalinities. The in situ K D values were compared with KD values predicted from a surface complexation model (SCM) developed under laboratory conditions in a separate study. A good agreement between the predicted and measured in situ KD values was observed. The demonstration that the laboratory derived SCM can predict U(VI) adsorption in the field provides a critical independent test of a submodel used in a reactive transport model. ?? 2004 Elsevier Ltd. All rights reserved.

KdV-like equations for fluid dynamics

NASA Astrophysics Data System (ADS)

Ruggieri, M.; Speciale, M. P.

2014-12-01

Main goal of the authors is to consider the generalized system of KdV equations ut+uxxx+2uux+2e1vvx+e2(uxv+uvx)+e3vxxx = 0 c1vt+vxxx+2vvx+c2vx+c3(e1(uxv+uvx)+2e2uux+e3uxxx) = 0 (1), and to construct the optimal system of one dimensional subalgebras. The reduction of the above system to ODEs through the optimal systems is performed and finally an application is shown.

Characterization of a monoclonal antibody (P40) against the 68 kD major allergen of Penicillium notatum.

PubMed

Shen, H D; Choo, K B; Chen, J H; Lin, W L; Chang, Z N; Han, S H

1992-04-01

A monoclonal antibody (MoAb P40) against the 68 kD major allergen of Penicillium notatum (P. notatum) was obtained by immunizing the mouse with a crude extract of P. notatum. Analysed by two-dimensional gel electrophoresis and immunoblotting, P40 reacted with two different isoforms of the 68 kD component of P. notatum with pIs of 5.4 and 5.5. In addition to P. notatum, P40 showed positive ELISA activity to Aspergillus fumigatus (A. fumigatus) but not to components of six other fungi including Alternaria porri, Cladosporium cladosporoides, Aureobasidium pullulans, Fusarium solani, Rhizopus arrhizus and Candida albicans. Analysed by ELISA, MoAb P40 also showed positive activity to two (P. frequentans and P. roseopurpureum) of the 10 other Penicillium species and two (A. terreus and A. flavus) of the four other Aspergillus species tested. SDS-PAGE and immunoblotting studies demonstrated P40 positive reactivity to components with MW of about 67 kD in all these Penicillium and Aspergillus species with positive ELISA activity to P40. Furthermore, immunoblotting activity of MoAb P40 to the 67 kD component of A. niger was also observed. The epitope of the 68 kD allergen of P. notatum recognized by MoAb P40 was resistant to treatment of periodate oxidation with concentration of NaIO4 up to 20 mM. This MoAb may thus be useful in the characterization and purification of the 68 kD allergen from crude extracts, and in the molecular cloning of allergen genes.

FAST TRACK COMMUNICATION Solving the ultradiscrete KdV equation

NASA Astrophysics Data System (ADS)

Willox, Ralph; Nakata, Yoichi; Satsuma, Junkichi; Ramani, Alfred; Grammaticos, Basile

2010-12-01

We show that a generalized cellular automaton, exhibiting solitonic interactions, can be explicitly solved by means of techniques first introduced in the context of the scattering problem for the KdV equation. We apply this method to calculate the phase-shifts caused by interactions between the solitonic and non-solitonic parts into which arbitrary initial states separate in time.

Clinical association between Kikuchi׳s disease and systemic lupus erythematosus: A systematic literature review.

PubMed

Sopeña, Bernardo; Rivera, Alberto; Chamorro, Antonio; Freire, Mayka; Alende, Vanessa; Seco, Elena; González-Gay, Miguel A; González-Quintela, Arturo

2017-08-01

To perform a systematic review of all cases of the association between Kikuchi's disease (KD) and systemic lupus erythematosus (SLE), and to ascertain the clinical and laboratory characteristics of this association (KD-SLE). We conducted a systematic search of the scientific literature until 31 January 2016. For study purposes, only patients aged >14 years, with histologically proven KD, definite SLE and adequate clinical data were included. To compare KD-SLE against isolated KD and SLE, we selected 2 large series of patients with KD and 4 series of SLE patients. The search found 158 adults with proven KD-SLE. Of these, 113 with sufficient clinical information were included; 86 were women (female:male ratio = 5.0); mean age at diagnosis was 34 years (range: 14-56 years); and an ethnic distribution of 50.5% Asian, 34% Caucasian, and 15% other. KD-SLE patients differed significantly from patients with isolated KD, presenting with a higher frequency of high fever (90%), severe KD (88%), and extranodal manifestations. When compared to patients with SLE, those with KD-SLE presented with a higher frequency of fever and systemic symptoms and a lower frequency of lupus nephritis (22%). SLE had been diagnosed before KD in 18% of cases, simultaneously in 51%, and after KD in 31%. No significant differences were found in terms of time of diagnosis. While KD-SLE patients share many clinical and laboratory manifestations with SLE, they differ in a lower frequency of lupus nephritis. The relative time of diagnosis of each disease did not affect the clinical expression of KD-SLE. Copyright © 2017 Elsevier Inc. All rights reserved.

[Kawasaki disease in children and adolescents].

PubMed

Neudorf, U

2011-12-01

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The diagnostic criteria are fulfilled with fever of unknown origin and 4 of the following 5 criteria: bilateral conjunctival injection, cervical lymphadenopathy, polymorphous rash, oral mucous membrane changes (injected lips, strawberry tongue) and peripheral extremity changes (erythema, edema, desquamation). If less than 4 criteria are found incomplete KD can be diagnosed. The therapy is 2 g/kg body weight single dose intravenous immunoglobulin and acetylsalicylic acid (ASS). In the long-term follow-up the main focus is on the coronary arteries because coronary changes play a key role in the intensity of long-term management. There is some evidence that KD is a risk factor for cardiovascular diseases in adults.

A systematic review of the etiopathogenesis of Kienböck's disease and a critical appraisal of its recognition as an occupational disease related to hand-arm vibration

PubMed Central

2012-01-01

Background We systematically reviewed etiological factors of Kienböck’s disease (osteonecrosis of the lunate) discussed in the literature in order to examine the justification for including Kienböck’s disease (KD) in the European Listing of Occupational Diseases. Methods We searched the Ovid/Medline and the Cochrane Library for articles discussing the etiology of osteonecrosis of the lunate published since the first description of KD in 1910 and up until July 2012 in English, French or German. Literature was classified by the level of evidence presented, the etiopathological hypothesis discussed, and the author's conclusion about the role of the etiopathological hypothesis. The causal relationship between KD and hand-arm vibration was elucidated by the Bradford Hill criteria. Results A total of 220 references was found. Of the included 152 articles, 140 (92%) reached the evidence level IV (case series). The four most frequently discussed factors were negative ulnar variance (n=72; 47%), primary arterial ischemia of the lunate (n=63; 41%), trauma (n=63; 41%) and hand-arm vibration (n=53; 35%). The quality of the cohort studies on hand-arm vibration did not permit a meta-analysis to evaluate the strength of an association to KD. Evidence for the lack of consistency, plausibility and coherence of the 4 most frequently discussed etiopathologies was found. No evidence was found to support any of the nine Bradford Hill criteria for a causal relationship between KD and hand-arm vibration. Conclusions A systematic review of 220 articles on the etiopathology of KD and the application of the Bradford Hill criteria does not provide sufficient scientific evidence to confirm or refute a causal relationship between KD and hand-arm vibration. This currently suggests that, KD does not comply with the criteria of the International Labour Organization determining occupational diseases. However, research with a higher level of evidence is required to further determine if hand

A systematic review of the etiopathogenesis of Kienböck's disease and a critical appraisal of its recognition as an occupational disease related to hand-arm vibration.

PubMed

Stahl, Stéphane; Stahl, Adelana Santos; Meisner, Christoph; Rahmanian-Schwarz, Afshin; Schaller, Hans-Eberhard; Lotter, Oliver

2012-11-21

We systematically reviewed etiological factors of Kienböck's disease (osteonecrosis of the lunate) discussed in the literature in order to examine the justification for including Kienböck's disease (KD) in the European Listing of Occupational Diseases. We searched the Ovid/Medline and the Cochrane Library for articles discussing the etiology of osteonecrosis of the lunate published since the first description of KD in 1910 and up until July 2012 in English, French or German. Literature was classified by the level of evidence presented, the etiopathological hypothesis discussed, and the author's conclusion about the role of the etiopathological hypothesis. The causal relationship between KD and hand-arm vibration was elucidated by the Bradford Hill criteria. A total of 220 references was found. Of the included 152 articles, 140 (92%) reached the evidence level IV (case series). The four most frequently discussed factors were negative ulnar variance (n=72; 47%), primary arterial ischemia of the lunate (n=63; 41%), trauma (n=63; 41%) and hand-arm vibration (n=53; 35%). The quality of the cohort studies on hand-arm vibration did not permit a meta-analysis to evaluate the strength of an association to KD. Evidence for the lack of consistency, plausibility and coherence of the 4 most frequently discussed etiopathologies was found. No evidence was found to support any of the nine Bradford Hill criteria for a causal relationship between KD and hand-arm vibration. A systematic review of 220 articles on the etiopathology of KD and the application of the Bradford Hill criteria does not provide sufficient scientific evidence to confirm or refute a causal relationship between KD and hand-arm vibration. This currently suggests that, KD does not comply with the criteria of the International Labour Organization determining occupational diseases. However, research with a higher level of evidence is required to further determine if hand-arm vibration is a risk factor for KD.

A Case of Infantile Kyrle-Flegel Disease in a 6-Year-Old Yemeni Girl.

PubMed

Alshami, Mohammad Ali; Mohana, Mona Jameel

2016-01-01

Kyrle disease (KD) and Flegel disease (FD) are rare variants of primary perforating dermatoses, characterized by transepidermal elimination of abnormal endogenous materials. We describe a 6-year-old Yemeni girl with a 2-year history of generalized asymptomatic, small, reddish-brown keratotic papules with a lenticular central keratotic plug. Although these features are synonymous with FD, the histology of a punch biopsy was consistent with KD. The patient was otherwise healthy, and no family members had a history of similar diseases. The patient was diagnosed with KD-FD, owing to the manifestation of features associated with both diseases.

A Case of Infantile Kyrle-Flegel Disease in a 6-Year-Old Yemeni Girl

PubMed Central

Alshami, Mohammad Ali; Mohana, Mona Jameel

2016-01-01

Kyrle disease (KD) and Flegel disease (FD) are rare variants of primary perforating dermatoses, characterized by transepidermal elimination of abnormal endogenous materials. We describe a 6-year-old Yemeni girl with a 2-year history of generalized asymptomatic, small, reddish-brown keratotic papules with a lenticular central keratotic plug. Although these features are synonymous with FD, the histology of a punch biopsy was consistent with KD. The patient was otherwise healthy, and no family members had a history of similar diseases. The patient was diagnosed with KD-FD, owing to the manifestation of features associated with both diseases. PMID:26933407

Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis

PubMed Central

Kimura, Yayoi; Yanagimachi, Masakatsu; Ino, Yoko; Aketagawa, Mao; Matsuo, Michie; Okayama, Akiko; Shimizu, Hiroyuki; Oba, Kunihiro; Morioka, Ichiro; Imagawa, Tomoyuki; Kaneko, Tetsuji; Yokota, Shumpei; Hirano, Hisashi; Mori, Masaaki

2017-01-01

Kawasaki disease (KD) is a systemic vasculitis and childhood febrile disease that can lead to cardiovascular complications. The diagnosis of KD depends on its clinical features, and thus it is sometimes difficult to make a definitive diagnosis. In order to identify diagnostic serum biomarkers for KD, we explored serum KD-related proteins, which differentially expressed during the acute and recovery phases of two patients by mass spectrometry (MS). We identified a total of 1,879 proteins by MS-based proteomic analysis. The levels of three of these proteins, namely lipopolysaccharide-binding protein (LBP), leucine-rich alpha-2-glycoprotein (LRG1), and angiotensinogen (AGT), were higher in acute phase patients. In contrast, the level of retinol-binding protein 4 (RBP4) was decreased. To confirm the usefulness of these proteins as biomarkers, we analyzed a total of 270 samples, including those collected from 55 patients with acute phase KD, by using western blot analysis and microarray enzyme-linked immunosorbent assays (ELISAs). Over the course of this experiment, we determined that the expression level of these proteins changes specifically in the acute phase of KD, rather than the recovery phase of KD or other febrile illness. Thus, LRG1 could be used as biomarkers to facilitate KD diagnosis based on clinical features. PMID:28262744

Screening Utility of the King-Devick Test in Mild Cognitive Impairment and Alzheimer Disease Dementia.

PubMed

Galetta, Kristin M; Chapman, Kimberly R; Essis, Maritza D; Alosco, Michael L; Gillard, Danielle; Steinberg, Eric; Dixon, Diane; Martin, Brett; Chaisson, Christine E; Kowall, Neil W; Tripodis, Yorghos; Balcer, Laura J; Stern, Robert A

2017-01-01

The King-Devick (K-D) test is a 1 to 2 minute, rapid number naming test, often used to assist with detection of concussion, but also has clinical utility in other neurological conditions (eg, Parkinson disease). The K-D involves saccadic eye and other eye movements, and abnormalities thereof may be an early indicator of Alzheimer disease (AD)-associated cognitive impairment. No study has tested the utility of the K-D in AD and we sought to do so. The sample included 206 [135 controls, 39 mild cognitive impairment (MCI), and 32 AD dementia] consecutive subjects from the Boston University Alzheimer's Disease Center registry undergoing their initial annual evaluation between March 2013 and July 2015. The K-D was administered during this period. Areas under the receiver operating characteristic curves generated from logistic regression models revealed the K-D test distinguished controls from subjects with cognitive impairment (MCI and AD dementia) [area under the curve (AUC)=0.72], MCI (AUC=0.71) and AD dementia (AUC=0.74). K-D time scores between 48 and 52 seconds were associated with high sensitivity (>90.0%) and negative predictive values (>85.0%) for each diagnostic group. The K-D correlated strongly with validated attention, processing speed, and visual scanning tests. The K-D test may be a rapid and simple effective screening tool to detect cognitive impairment associated with AD.

Lack of association between miR-218 rs11134527 A>G and Kawasaki disease susceptibility.

PubMed

Pi, Lei; Fu, Lanyan; Xu, Yufen; Che, Di; Deng, Qiulian; Huang, Xijing; Li, Meiai; Zhang, Li; Huang, Ping; Gu, Xiaoqiong

2018-05-01

Abstract Kawasaki disease (KD) is a type of disease that includes the development of a fever that lasts at least five days and involves the clinical manifestation of multicellular vasculitis. KD has become one of the most common pediatric cardiovascular diseases. Previous studies have reported that miR-218 rs11134527 A>G is associated with susceptibility to various cancer risks. However, there is a lack of evidence regarding the relationship between this polymorphism and KD risk. This study explored the correlation between the miR-218 rs11134527 A>G polymorphism and the risk of KD. We recruited 532 patients with KD and 623 controls to genotype the miR-218 rs11134527 A>G polymorphism with a TaqMan allelic discrimination assay. Our results illustrated that the miR-218 rs11134527 A>G polymorphism was not associated with KD risk. In an analysis stratified by age, sex, and coronary artery lesions, we found only that the risk of KD was significantly decreased for children older than 5 years (GG vs. AA/AG: adjusted OR=0.26, 95% CI=0.07-0.94, P =0.041). This study demonstrated that the miR-218 rs1113452 A>G polymorphism may have an age-related relationship with KD susceptibility that has not previously been revealed. ©2018 The Author(s).

Structural basis of clade-specific HIV-1 neutralization by humanized anti-V3 monoclonal antibody KD-247.

PubMed

Kirby, Karen A; Ong, Yee Tsuey; Hachiya, Atsuko; Laughlin, Thomas G; Chiang, Leslie A; Pan, Yun; Moran, Jennifer L; Marchand, Bruno; Singh, Kamalendra; Gallazzi, Fabio; Quinn, Thomas P; Yoshimura, Kazuhisa; Murakami, Toshio; Matsushita, Shuzo; Sarafianos, Stefan G

2015-01-01

Humanized monoclonal antibody KD-247 targets the Gly(312)-Pro(313)-Gly(314)-Arg(315) arch of the third hypervariable (V3) loop of the HIV-1 surface glycoprotein. It potently neutralizes many HIV-1 clade B isolates, but not of other clades. To understand the molecular basis of this specificity, we solved a high-resolution (1.55 Å) crystal structure of the KD-247 antigen binding fragment and examined the potential interactions with various V3 loop targets. Unlike most antibodies, KD-247 appears to interact with its target primarily through light chain residues. Several of these interactions involve Arg(315) of the V3 loop. To evaluate the role of light chain residues in the recognition of the V3 loop, we generated 20 variants of KD-247 single-chain variable fragments with mutations in the antigen-binding site. Purified proteins were assessed for V3 loop binding using AlphaScreen technology and for HIV-1 neutralization. Our data revealed that recognition of the clade-specificity defining residue Arg(315) of the V3 loop is based on a network of interactions that involve Tyr(L32), Tyr(L92), and Asn(L27d) that directly interact with Arg(315), thus elucidating the molecular interactions of KD-247 with its V3 loop target. © FASEB.

Transforming Growth Factor-β Signaling Pathway in Patients with Kawasaki Disease

PubMed Central

Shimizu, Chisato; Jain, Sonia; Lin, Kevin O.; Molkara, Delaram; Frazer, Jeffrey R.; Sun, Shelly; Baker, Annette L.; Newburger, Jane W.; Rowley, Anne H.; Shulman, Stanford T.; Davila, Sonia; Hibberd, Martin L.; Burgner, David; Breunis, Willemijn B.; Kuijpers, Taco W.; Wright, Victoria J.; Levin, Michael; Eleftherohorinou, Hariklia; Coin, Lachlan; Popper, Stephen J.; Relman, David A.; Fury, Wen; Lin, Calvin; Mellis, Scott; Tremoulet, Adriana H.; Burns, Jane C.

2011-01-01

Background Transforming growth factor (TGF)-β is a multifunctional peptide that is important in T-cell activation and cardiovascular remodeling, both of which are important features of Kawasaki disease (KD). We postulated that variation in TGF-β signaling might be important in KD susceptibility and disease outcome. Methods and Results We investigated genetic variation in 15 genes belonging to the TGF-β pathway in a total 771 KD subjects of mainly European descendent from the US, UK, Australia and the Netherlands. We analyzed transcript abundance patterns using microarray and RT-PCR for these same genes and measured TGF-β2 protein levels in plasma. Genetic variants in TGFB2, TGFBR2 and SMAD3 and their haplotypes were consistently and reproducibly associated with KD susceptibility, coronary artery aneurysm formation, aortic root dilatation, and intravenous immunoglobulin treatment response in different cohorts. A SMAD3 haplotype associated with KD susceptibility replicated in two independent cohorts and an intronic SNP in a separate haplotype block was also strongly associated (A/G, rs4776338) (p=0.000022, OR 1.50, 95% CI 1.25-1.81). Pathway analysis using all 15 genes further confirmed the importance of the TGF-β pathway in KD pathogenesis. Whole blood transcript abundance for these genes and TGF-β2 plasma protein levels changed dynamically over the course of the illness. Conclusions These studies suggest that genetic variation in the TGF-β pathway influences KD susceptibility, disease outcome, and response to therapy and that aortic root and coronary artery Z scores can be used for phenotype/genotype analyses. Analysis of transcript abundance and protein levels further support the importance of this pathway in KD pathogenesis. PMID:21127203

Increased Kawasaki Disease Incidence Associated With Higher Precipitation and Lower Temperatures, Japan, 1991-2004.

PubMed

Abrams, Joseph Y; Blase, Jennifer L; Belay, Ermias D; Uehara, Ritei; Maddox, Ryan A; Schonberger, Lawrence B; Nakamura, Yosikazu

2018-06-01

Kawasaki disease (KD) is an acute febrile vasculitis, which primarily affects children. The etiology of KD is unknown; while certain characteristics of the disease suggest an infectious origin, genetic or environmental factors may also be important. Seasonal patterns of KD incidence are well documented, but it is unclear whether these patterns are caused by changes in climate or by other unknown seasonal effects. The relationship between KD incidence and deviations from expected temperature and precipitation were analyzed using KD incidence data from Japanese nationwide epidemiologic surveys (1991-2004) and climate data from 136 weather stations of the Japan Meteorological Agency. Seven separate Poisson-distributed generalized linear regression models were run to examine the effects of temperature and precipitation on KD incidence in the same month as KD onset and the previous 1, 2, 3, 4, 5 and 6 months, controlling for geography as well as seasonal and long-term trends in KD incidence. KD incidence was negatively associated with temperature in the previous 2, 3, 4 and 5 months and positively associated with precipitation in the previous 1 and 2 months. The model that best predicted variations in KD incidence used climate data from the previous 2 months. An increase in total monthly precipitation by 100 mm was associated with increased KD incidence (rate ratio [RR] 1.012, 95% confidence interval [CI]: 1.005-1.019), and an increase of monthly mean temperature by 1°C was associated with decreased KD incidence (RR 0.984, 95% CI: 0.978-0.990). KD incidence was significantly affected by temperature and precipitation in previous months independent of other unknown seasonal factors. Climate data from the previous 2 months best predicted the variations in KD incidence. Although fairly minor, the effect of temperature and precipitation independent of season may provide additional clues to the etiology of KD.

On the exact solutions of high order wave equations of KdV type (I)

NASA Astrophysics Data System (ADS)

Bulut, Hasan; Pandir, Yusuf; Baskonus, Haci Mehmet

2014-12-01

In this paper, by means of a proper transformation and symbolic computation, we study high order wave equations of KdV type (I). We obtained classification of exact solutions that contain soliton, rational, trigonometric and elliptic function solutions by using the extended trial equation method. As a result, the motivation of this paper is to utilize the extended trial equation method to explore new solutions of high order wave equation of KdV type (I). This method is confirmed by applying it to this kind of selected nonlinear equations.

Multi-hump bright solitons in a Schrödinger-mKdV system

NASA Astrophysics Data System (ADS)

Cisneros-Ake, Luis A.; Parra Prado, Hugo; López Villatoro, Diego Joselito; Carretero-González, R.

2018-03-01

We consider the problem of energy transport in a Davydov model along an anharmonic crystal medium obeying quartic longitudinal interactions corresponding to rigid interacting particles. The Zabusky and Kruskal unidirectional continuum limit of the original discrete equations reduces, in the long wave approximation, to a coupled system between the linear Schrödinger (LS) equation and the modified Korteweg-de Vries (mKdV) equation. Single- and two-hump bright soliton solutions for this LS-mKdV system are predicted to exist by variational means and numerically confirmed. The one-hump bright solitons are found to be the anharmonic supersonic analogue of the Davydov's solitons while the two-hump (in both components) bright solitons are found to be a novel type of soliton consisting of a two-soliton solution of mKdV trapped by the wave function associated to the LS equation. This two-hump soliton solution, as a two component solution, represents a new class of polaron solution to be contrasted with the two-soliton interaction phenomena from soliton theory, as revealed by a variational approach and direct numerical results for the two-soliton solution.

An Algebraic Construction of the First Integrals of the Stationary KdV Hierarchy

NASA Astrophysics Data System (ADS)

Matsushima, Masatomo; Ohmiya, Mayumi

2009-09-01

The stationary KdV hierarchy is constructed using a kind of recursion operator called Λ-operator. The notion of the maximal solution of the n-th stationary KdV equation is introduced. Using this maximal solution, a specific differential polynomial with the auxiliary spectral parameter called the spectral M-function is constructed as the quadratic form of the fundamental system of the eigenvalue problem for the 2-nd order linear ordinary differential equation which is related to the linearizing operator of the hierarchy. By calculating a perfect square condition of the quadratic form by an elementary algebraic method, the complete set of first integrals of this hierarchy is constructed.

Characterization of T cell repertoire changes in acute Kawasaki disease

PubMed Central

1993-01-01

Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that is associated with marked activation of T cells and monocyte/macrophages. Using a quantitative polymerase chain reaction (PCR) technique, we recently found that the acute phase of KD is associated with the expansion of T cells expressing the V beta 2 and V beta 8.1 gene segments. In the present work, we used a newly developed anti-V beta 2 monoclonal antibody (mAb) and studied a new group of KD patients to extend our previous PCR results. Immunofluorescence analysis confirmed that V beta 2-bearing T cells are selectively increased in patients with acute KD. The increase occurred primarily in the CD4 T cell subset. The percentages of V beta 2+ T cells as determined by mAb reactivity and flow cytometry correlated linearly with V beta expression as quantitated by PCR. However, T cells from acute KD patients appeared to express proportionately higher levels of V beta 2 transcripts per cell as compared with healthy controls or convalescent KD patients. Sequence analysis of T cell receptor beta chain genes of V beta 2 and V beta 8.1 expressing T cells from acute KD patients showed extensive junctional region diversity. These data showing polyclonal expansion of V beta 2+ and V beta 8+ T cells in acute KD provide additional insight into the immunopathogenesis of this disease. PMID:8094737

Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease.

PubMed

Jaggi, Preeti; Mejias, Asuncion; Xu, Zhaohui; Yin, Han; Moore-Clingenpeel, Melissa; Smith, Bennett; Burns, Jane C; Tremoulet, Adriana H; Jordan-Villegas, Alejandro; Chaussabel, Damien; Texter, Karen; Pascual, Virginia; Ramilo, Octavio

2018-01-01

Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4-6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG.

Seasonality of Kawasaki Disease: A Global Perspective

PubMed Central

Burns, Jane C.; Herzog, Lauren; Fabri, Olivia; Tremoulet, Adriana H.; Rodó, Xavier; Uehara, Ritei; Burgner, David; Bainto, Emelia; Pierce, David; Tyree, Mary; Cayan, Daniel

2013-01-01

Background Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. Methods Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. Results A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. Conclusion Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter

Seasonality of Kawasaki disease: a global perspective.

PubMed

Burns, Jane C; Herzog, Lauren; Fabri, Olivia; Tremoulet, Adriana H; Rodó, Xavier; Uehara, Ritei; Burgner, David; Bainto, Emelia; Pierce, David; Tyree, Mary; Cayan, Daniel

2013-01-01

Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter months in the Northern Hemisphere extra-tropics.

Uranium partition coefficients (Kd) in forest surface soil reveal long equilibrium times and vary by site and soil size fraction.

PubMed

Whicker, Jeffrey J; Pinder, John E; Ibrahim, Shawki A; Stone, James M; Breshears, David D; Baker, Kristine N

2007-07-01

The environmental mobility of newly deposited radionuclides in surface soil is driven by complex biogeochemical relationships, which have significant impacts on transport pathways. The partition coefficient (Kd) is useful for characterizing the soil-solution exchange kinetics and is an important factor for predicting relative amounts of a radionuclide transported to groundwater compared to that remaining on soil surfaces and thus available for transport through erosion processes. Measurements of Kd for 238U are particularly useful because of the extensive use of 238U in military applications and associated testing, such as done at Los Alamos National Laboratory (LANL). Site-specific measurements of Kd for 238U are needed because Kd is highly dependent on local soil conditions and also on the fine soil fraction because 238U concentrates onto smaller soil particles, such as clays and soil organic material, which are most susceptible to wind erosion and contribute to inhalation exposure in off-site populations. We measured Kd for uranium in soils from two neighboring semiarid forest sites at LANL using a U.S. Environmental Protection Agency (EPA)-based protocol for both whole soil and the fine soil fraction (diameters<45 microm). The 7-d Kd values, which are those specified in the EPA protocol, ranged from 276-508 mL g-1 for whole soil and from 615-2249 mL g-1 for the fine soil fraction. Unexpectedly, the 30-d Kd values, measured to test for soil-solution exchange equilibrium, were more than two times the 7-d values. Rates of adsorption of 238U to soil from solution were derived using a 2-component (FAST and SLOW) exponential model. We found significant differences in Kd values among LANL sampling sites, between whole and fine soils, and between 7-d and 30-d Kd measurements. The significant variation in soil-solution exchange kinetics among the soils and soil sizes promotes the use of site-specific data for estimates of environmental transport rates and suggests

Epidemiologic survey of Kawasaki disease in Inner Mongolia, China, between 2001 and 2013

PubMed Central

Zhang, Xiaomei; Liang, Yanyan; Feng, Wanyu; Su, Xuewen; Zhu, Hua

2016-01-01

The epidemiologic features of Kawasaki disease (KD) in the Inner Mongolia Autonomous Region of China has not been previously determined, to the best of our knowledge. Therefore, the aim of the present study was to investigate the epidemiology of KD in Inner Mongolia. Clinical data from 518 patients treated for KD in Inner Mongolia between January 2001 and December 2013 were analyzed. The results indicated that the mean annual incidence rate was 3.55±2.96 per 100,000 children under the age of 5 years between 2001 and 2013. The age at diagnosis ranged between 49 days and 14 years, while the disease occurred more frequently in the spring and summer. In addition, the incidence of coronary artery lesion (CAL) was reported to be 40.2% in the present survey. KD patients in the Han Chinese ethnic group were more likely to be complicated by CAL, whereas patients with incidence of KD in July were less likely to be complicated by CAL. In conclusion, the incidence of KD was observed to be increasing in Inner Mongolia, while the ethnic group and month of onset may be associated with the incidence of CAL in KD patients. PMID:27446347

The epidemiology of Kawasaki disease: a global update.

PubMed

Singh, Surjit; Vignesh, Pandiarajan; Burgner, David

2015-11-01

Kawasaki disease (KD) is a childhood vasculitis and the most frequent cause of paediatric acquired heart disease in North America, Europe and Japan. It is increasingly recognised in rapidly industrialising countries such as China and India where it may replace rheumatic heart disease as the most common cause of acquired heart disease in children. We review the current global epidemiology of KD and discuss some public health implications. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Bimodal pair f-KdV dynamics in star-forming clouds

NASA Astrophysics Data System (ADS)

Karmakar, Pralay Kumar; Haloi, Archana; Roy, Supriya

2018-04-01

A theoretical formalism for investigating the bimodal conjugational mode dynamics of hybrid source, dictated by a unique pair of forced Korteweg-de Vries (f-KdV) equations in a complex turbo-magnetized star-forming cloud, is reported. It uses a standard multi-scale analysis executed over the cloud-governing equations in a closure form to derive the conjugated pair f-KdV system. We numerically see the structural features of two distinctive classes of eigenmode patterns stemming from the conjoint gravito-electrostatic interplay. The electrostatic compressive monotonic aperiodic shock-like patterns and gravitational compressive non-monotonic oscillatory shock-like structures are excitable. It is specifically revealed that the constitutive grain-charge (grain-mass) acts as electrostatic stabilizer (gravitational destabilizer) against the global cloud collapse dynamics. The basic features of the nonlinear coherent structures are confirmed in systematic phase-plane landscapes, indicating electrostatic irregular non-homoclinic open trajectories and gravitational atypical non-chaotic homoclinic fixed-point attractors. The relevance in the real astro-cosmic scenarios of the early phases of structure formation via wave-driven fluid-accretive transport processes is summarily emphasized.

Soy isoflavone intake is associated with risk of Kawasaki disease

PubMed Central

Portman, Michael A.; Navarro, Sandi L.; Bruce, Margaret E.; Lampe, Johanna W.

2016-01-01

Kawasaki disease (KD) is an acute vasculitis affecting children. Incidence of KD varies according to ethnicity and is highest in Asian populations. Although genetic differences may explain this variation, dietary or environmental factors could also be responsible. The objectives of this study were to determine dietary soy and isoflavone consumption in a cohort of KD children just before disease onset and their mothers' intake during pregnancy and nursing. We tested the hypothesis that soy isoflavone consumption is associated with risk of KD in US children, potentially explaining some of the ethnic-cultural variation in incidence. We evaluated soy food intake and isoflavone consumption in nearly 200 US KD cases and 200 age-matched controls using a food frequency questionnaire for children and in their mothers. We used a logistic regression model to test the association of isoflavones and KD. Maternal surveys on soy intake during pregnancy and nursing showed no significant differences in isoflavone consumption between groups. However, we identified significantly increased KD risk in children for total isoflavone (odds ratio [OR], 2.33; 95%confidence interval [CI], 1.37–3.96) and genistein (OR, 2.46; 95% CI, 1.46–4.16) intakes, when comparing high soy consumers vs nonconsumers. In addition, significantly increased KD risk occurred in Asian-American children with the highest consumption (total isoflavones: OR, 7.29; 95% CI, 1.73–30.75; genistein: OR, 8.33; 95% CI, 1.92–36.24) compared to whites. These findings indicate that childhood dietary isoflavone consumption, but not maternal isoflavone intake during pregnancy and nursing, relates to KD risk in an ethnically diverse US population. PMID:27440537

Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease

PubMed Central

Xu, Zhaohui; Yin, Han; Moore-Clingenpeel, Melissa; Smith, Bennett; Burns, Jane C.; Tremoulet, Adriana H.; Jordan-Villegas, Alejandro; Chaussabel, Damien; Texter, Karen; Pascual, Virginia; Ramilo, Octavio

2018-01-01

Background Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Methods Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4–6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. Results We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. Conclusion A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG. PMID:29813106

The k-d Tree: A Hierarchical Model for Human Cognition.

ERIC Educational Resources Information Center

Vandendorpe, Mary M.

This paper discusses a model of information storage and retrieval, the k-d tree (Bentley, 1975), a binary, hierarchical tree with multiple associate terms, which has been explored in computer research, and it is suggested that this model could be useful for describing human cognition. Included are two models of human long-term memory--networks and…

An auto-Bäcklund transformation and exact solutions for Wick-type stochastic generalized KdV equations

NASA Astrophysics Data System (ADS)

Xie, Yingchao

2004-05-01

Wick-type stochastic generalized KdV equations are researched. By using the homogeneous balance, an auto-Bäcklund transformation to the Wick-type stochastic generalized KdV equations is derived. And stochastic single soliton and stochastic multi-soliton solutions are shown by using the Hermite transform. Research supported by the National Natural Science Foundation of China (19971072) and the Natural Science Foundation of Education Committee of Jiangsu Province of China (03KJB110135).

Slower saccadic reading in Parkinson's disease.

PubMed

Jehangir, Naz; Yu, Caroline Yizhu; Song, Jeehey; Shariati, Mohammad Ali; Binder, Steven; Beyer, Jill; Santini, Veronica; Poston, Kathleen; Liao, Yaping Joyce

2018-01-01

Idiopathic Parkinson's Disease (PD) is characterized by degeneration of dopaminergic and other neurons, leading to motor and non-motor deficits. Abnormal eye movements in PD, including fixations, saccades, and convergence, are well described. However, saccadic reading, which requires serial and alternating saccades and fixations, is not well studied, despite its obvious impact on the quality of life. In this study, we assessed saccadic reading using variations of the King-Devick (KD) test, a rapid single digit number naming test, as a way to assess the ability to make serial left-to-right ocular motor movements necessary for reading. We recruited 42 treated PD patients and 80 age-matched controls and compared their reading times with a variety of measures, including age, duration of disease, Unified Parkinson's Disease Rating Scale (UPDRS), the National Eye Institute 25-Item Visual Functioning Questionnaire 25 (VFQ-25), and Montreal Cognitive assessment (MoCA) test. The subjects performed 4 trials of reading 120 single digit numbers aloud as fast as possible without making errors. In each trial, they read 3 pages (KD1, KD2, and KD3), and each page contained 40 numbers per page in 8 lines with 5 numbers/line. We found that PD patients read about 20% slower than controls on all tests (KD1, 2, and 3 tests) (p < 0.02), and both groups read irregularly spaced numbers slower than regularly spaced numbers. Having lines between numbers to guide reading (KD1 tests) did not impact reading time in both PD and controls, but increased visual crowding as a result of decreased spacing between numbers (KD3 tests) was associated with significantly slower reading times in both PD and control groups. Our study revealed that saccadic reading is slower in PD, but controls and PD patients are both impacted by visuospatial planning challenges posed by increased visual crowding and irregularity of number spacing. Reading time did not correlate with UPDRS or MoCA scores in PD patients but

GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease

PubMed Central

McKenzie, Brent S.

2016-01-01

Kawasaki disease (KD) is the leading cause of pediatric heart disease in developed countries. KD patients develop cardiac inflammation, characterized by an early infiltrate of neutrophils and monocytes that precipitates coronary arteritis. Although the early inflammatory processes are linked to cardiac pathology, the factors that regulate cardiac inflammation and immune cell recruitment to the heart remain obscure. In this study, using a mouse model of KD (induced by a cell wall Candida albicans water-soluble fraction [CAWS]), we identify an essential role for granulocyte/macrophage colony-stimulating factor (GM-CSF) in orchestrating these events. GM-CSF is rapidly produced by cardiac fibroblasts after CAWS challenge, precipitating cardiac inflammation. Mechanistically, GM-CSF acts upon the local macrophage compartment, driving the expression of inflammatory cytokines and chemokines, whereas therapeutically, GM-CSF blockade markedly reduces cardiac disease. Our findings describe a novel role for GM-CSF as an essential initiating cytokine in cardiac inflammation and implicate GM-CSF as a potential target for therapeutic intervention in KD. PMID:27595596

Technetium, Iodine, and Chromium Adsorption/Desorption Kd Values for Vadose Zone Pore Water, ILAW Glass, and Cast Stone Leachates Contacting an IDF Sand Sequence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Last, George V.; Snyder, Michelle M.V.; Um, Wooyong

Performance and risk assessments of immobilized low-activity waste (ILAW) at the Integrated Disposal Facility (IDF) have shown that risks to groundwater are quite sensitive to adsorption-desorption interactions occurring in the near- and far-field environment. These interactions between the underlying sediments and the contaminants present in the leachates that descend from the buried glass, secondary waste grouts, and potentially Cast Stone low-activity waste packages have been represented in these assessments using the contaminant distribution coefficient (Kd) construct. Some contaminants (99Tc, 129I, and Cr) present in significant quantities in these wastes have low Kd values and tend to drive risk to publicmore » health and the environment. Relatively small changes in the Kd value can cause relatively large changes in the retardation factor. Thus, even relatively small uncertainty in the Kd value can result in a relatively large uncertainty in the risk determined through performance assessment modeling. The purpose of this study is to further reduce the uncertainty in Kd values for 99Tc, iodine (iodide and iodate), and Cr (chromate; CrO42-) by conducting systematic adsorption-desorption experiments using actual sand-dominated Hanford formation sediments from beneath the IDF and solutions that closely mimic Hanford vadose zone pore water and leachates from Cast Stone and ILAW glass waste forms. Twenty-four batch and 21 flow-through column experiments were conducted, yielding 261 Kd measurements for these key contaminants, and contributing to our understanding for predicting transport from wastes disposed to the IDF. While the batch Kd methodology is not well-suited for measuring Kd values for non-sorbing species (as noted by the U.S. Environmental Protection Agency), the batch Kd results presented here are not wholly inconsistent with the column Kd results, and could be used for sensitivity purposes. Results from the column experiments are consistent with the

A Pilot Study Evaluating Cerebral Vasculitis in Kawasaki's Disease.

PubMed

Yeom, Jung Sook; Cho, Young Hye; Koo, Chung Mo; Jun, Jin Su; Park, Ji Sook; Park, Eun Sil; Seo, Ji-Hyun; Lim, Jae-Young; Woo, Hyang-Ok; Youn, Hee-Shang

2018-06-18

Cerebral vasculitis is thought to be a possible underlying mechanism of severe neurological complications of Kawasaki's disease (KD), such as cerebral infarct or aneurysm rupture. To evaluate the intracranial inflammatory response in patients with acute-stage KD, we measured the levels of cytokines (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) and pentraxin-3 (PTX3) in the cerebrospinal fluid of patients with KD ( n  = 7) and compared the levels to those of the age- and sex-matched febrile control patients (bacterial meningitis [ n  = 5], enteroviral meningitis [ n  = 10], nonspecific viral illness without central nervous system involvement [ n  = 10]). PTX3 and TNF-α were rarely detected and only in trace concentration in KD, and the levels of IL-6 were not different from those of nonspecific viral illnesses. These mediators are not established biomarkers for cerebral vasculitis but might reflect vascular inflammation in various diseases including KD. Therefore, intracranial inflammation including vasculitis seems to be insignificant in our patients with KD. However, our results might be attributed to the fact that these patients lacked any clinical signs of cerebral or coronary vessel involvement. None of them underwent brain imaging. To clarify this issue, further studies involving patients with neurologic symptoms and proven involvement of cerebral vessels are needed. Georg Thieme Verlag KG Stuttgart · New York.

The biophysical properties of the aorta are altered following Kawasaki disease.

PubMed

Vaujois, Laurence; Dallaire, Frédéric; Maurice, Roch L; Fournier, Anne; Houde, Christine; Thérien, Johanne; Cartwright, Daniel; Dahdah, Nagib

2013-12-01

The long-term sequelae of Kawasaki disease (KD) are based on the coronary complications. Because KD causes generalized vasculitis, with documented aneurysms in the femoral, iliac, renal, axillary, and brachial arteries, the aim of this study was to assess the biophysical properties of the aorta (BPA) after KD. The BPA are biometric measurements representing vascular structural and dynamic changes in response to cardiac work. Anthropometric and echocardiographic measurements of the aorta in a series of patients with KD were compared with those of healthy subjects. The BPA were calculated noninvasively by extrapolating previously validated equations that were conceived for invasive measurements. Because BPA vary with body habitus, control subjects were used to normalize BPA parameters for height to compute BPA Z-score equations. Between June 2007 and February 2010, BPA were recorded in 57 patients with KD >1 year after the onset of the disease, 45 without and 12 with coronary artery sequelae. The mean intervals between the acute onset of KD and enrollment were 10.0 ± 5.0 and 5.8 ± 4.5 years for patients with and without coronary artery sequelae, respectively (P = .008). Patients with KD with coronary artery sequelae had significantly altered Z scores of aortic diameter modulation, Peterson's elastic modulus, and β stiffness index (P = .001-.016). Patients with KD without coronary artery sequelae also exhibited altered elasticity, stiffness, and pulse-wave velocity (P = .001-.026). Altered BPA after KD are detectible despite apparent resolution of acute vasculitis. Future directions toward determining multilevel and multilayer vascular impact, including vascular autonomous homeostasis, require thorough investigation. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Lymphocyte and neuronal antigens in neuropsychiatric lupus: presence of an elutable, immunoprecipitable lymphocyte/neuronal 52 kd reactivity.

PubMed Central

Denburg, J A; Behmann, S A

1994-01-01

OBJECTIVE--To examine specific lymphocyte or neuronal antigens immuno-precipitated by systemic lupus erythematosus (SLE) sera. METHOD--SLE sera were screened for the presence of antibodies binding to surface antigens of CD4(+) HUT-78 or SK-N-SH and IMR-6 neuroblastoma cells using Western blotting or radioimmunoprecipitation. RESULTS--IgG eluates from both lymphocytes and neuroblastoma cells recognised a 52 kd band in HUT 78 cell lysates. Eight sera studied further using radioimmunoprecipitation also demonstrated binding to a 52 kd antigen (4/8 on HUT-78, 8/8 on SK-N-SH cells), partially depleted by absorption with viable HUT-78. CONCLUSION--A 52 kd antigen recognised by SLE sera on lymphocytes and neuronal cells may play a role in the pathogenesis of neuropsychiatric-SLE. Images PMID:8017983

Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease.

PubMed

Konno, Yuuki; Takahashi, Ikuko; Narita, Ayuko; Takeda, Osamu; Koizumi, Hiromi; Tamura, Masamichi; Kikuchi, Wataru; Komatsu, Akira; Tamura, Hiroaki; Tsuchida, Satoko; Noguchi, Atsuko; Takahashi, Tsutomu

2015-10-01

Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD.

Whole genome sequencing of an African American family highlights toll like receptor 6 variants in Kawasaki disease susceptibility.

PubMed

Kim, Jihoon; Shimizu, Chisato; Kingsmore, Stephen F; Veeraraghavan, Narayanan; Levy, Eric; Ribeiro Dos Santos, Andre M; Yang, Hai; Flatley, Jay; Hoang, Long Truong; Hibberd, Martin L; Tremoulet, Adriana H; Harismendy, Olivier; Ohno-Machado, Lucila; Burns, Jane C

2017-01-01

Kawasaki disease (KD) is the most common acquired pediatric heart disease. We analyzed Whole Genome Sequences (WGS) from a 6-member African American family in which KD affected two of four children. We sought rare, potentially causative genotypes by sequentially applying the following WGS filters: sequence quality scores, inheritance model (recessive homozygous and compound heterozygous), predicted deleteriousness, allele frequency, genes in KD-associated pathways or with significant associations in published KD genome-wide association studies (GWAS), and with differential expression in KD blood transcriptomes. Biologically plausible genotypes were identified in twelve variants in six genes in the two affected children. The affected siblings were compound heterozygous for the rare variants p.Leu194Pro and p.Arg247Lys in Toll-like receptor 6 (TLR6), which affect TLR6 signaling. The affected children were also homozygous for three common, linked (r2 = 1) intronic single nucleotide variants (SNVs) in TLR6 (rs56245262, rs56083757 and rs7669329), that have previously shown association with KD in cohorts of European descent. Using transcriptome data from pre-treatment whole blood of KD subjects (n = 146), expression quantitative trait loci (eQTL) analyses were performed. Subjects homozygous for the intronic risk allele (A allele of TLR6 rs56245262) had differential expression of Interleukin-6 (IL-6) as a function of genotype (p = 0.0007) and a higher erythrocyte sedimentation rate at diagnosis. TLR6 plays an important role in pathogen-associated molecular pattern recognition, and sequence variations may affect binding affinities that in turn influence KD susceptibility. This integrative genomic approach illustrates how the analysis of WGS in multiplex families with a complex genetic disease allows examination of both the common disease-common variant and common disease-rare variant hypotheses.

Can a systems biology approach unlock the mysteries of Kawasaki disease?

PubMed

Rowley, Anne H

2013-01-01

Kawasaki disease (KD) is a systemic inflammatory illness of childhood that particularly affects the coronary arteries. It can lead to coronary artery aneurysms, myocardial infarction, and sudden death. Clinical and epidemiologic data support an infectious cause, and the etiology remains unknown, but recent data support infection with a 'new' virus. Genetic factors influence KD susceptibility; the incidence is 10-fold higher in children of Asian when compared with Caucasian ethnicity. Recent research has identified genes affecting immune response that are associated with KD susceptibility and outcome. A re-examination of the pathologic features of KD has yielded a three process model of KD vasculopathy, providing a framework for understanding the KD arterial immune response and the damage it inflicts and for identifying new therapeutic targets for KD patients with coronary artery abnormalities. The researcher is faced with many challenges in determining the pathogenesis of KD. A systems biology approach incorporating genomics, proteomics, transcriptomics, and microbial bioinformatics analysis of high-throughput sequence data from KD tissues could provide the keys to unlocking the mysteries of this potentially fatal illness of childhood. Copyright © 2013 Wiley Periodicals, Inc.

Slower saccadic reading in Parkinson’s disease

PubMed Central

Jehangir, Naz; Yu, Caroline Yizhu; Song, Jeehey; Shariati, Mohammad Ali; Binder, Steven; Beyer, Jill; Santini, Veronica; Poston, Kathleen

2018-01-01

Idiopathic Parkinson’s Disease (PD) is characterized by degeneration of dopaminergic and other neurons, leading to motor and non-motor deficits. Abnormal eye movements in PD, including fixations, saccades, and convergence, are well described. However, saccadic reading, which requires serial and alternating saccades and fixations, is not well studied, despite its obvious impact on the quality of life. In this study, we assessed saccadic reading using variations of the King-Devick (KD) test, a rapid single digit number naming test, as a way to assess the ability to make serial left-to-right ocular motor movements necessary for reading. We recruited 42 treated PD patients and 80 age-matched controls and compared their reading times with a variety of measures, including age, duration of disease, Unified Parkinson’s Disease Rating Scale (UPDRS), the National Eye Institute 25-Item Visual Functioning Questionnaire 25 (VFQ-25), and Montreal Cognitive assessment (MoCA) test. The subjects performed 4 trials of reading 120 single digit numbers aloud as fast as possible without making errors. In each trial, they read 3 pages (KD1, KD2, and KD3), and each page contained 40 numbers per page in 8 lines with 5 numbers/line. We found that PD patients read about 20% slower than controls on all tests (KD1, 2, and 3 tests) (p < 0.02), and both groups read irregularly spaced numbers slower than regularly spaced numbers. Having lines between numbers to guide reading (KD1 tests) did not impact reading time in both PD and controls, but increased visual crowding as a result of decreased spacing between numbers (KD3 tests) was associated with significantly slower reading times in both PD and control groups. Our study revealed that saccadic reading is slower in PD, but controls and PD patients are both impacted by visuospatial planning challenges posed by increased visual crowding and irregularity of number spacing. Reading time did not correlate with UPDRS or MoCA scores in PD patients

Revisiting the role of environmental and climate factors on the epidemiology of Kawasaki disease.

PubMed

Rodó, Xavier; Ballester, Joan; Curcoll, Roger; Boyard-Micheau, Joseph; Borràs, Sílvia; Morguí, Josep-Anton

2016-10-01

Can environmental factors, such as air-transported preformed toxins, be of key relevance to the health outcomes of poorly understood human ailments (e.g., rheumatic diseases such as vasculitides, some inflammatory diseases, or even severe childhood acquired heart diseases)? Can the physical, chemical, or biological features of air masses be linked to the emergence of diseases such as Kawasaki disease (KD), Henoch-Schönlein purpura, Takayasu's aortitis, and ANCA-associated vasculitis? These diseases surprisingly share some common epidemiological features. For example, they tend to appear as clusters of cases grouped geographically and temporarily progress in nonrandom sequences that repeat every year in a similar way. They also show concurrent trend changes within regions in countries and among different world regions. In this paper, we revisit transdisciplinary research on the role of environmental and climate factors in the epidemiology of KD as a paradigmatic example of this group of diseases. Early-warning systems based on environmental alerts, if successful, could be implemented as a way to better inform patients who are predisposed to, or at risk for, developing KD. Further research on the etiology of KD could facilitate the development of vaccines and specific medical therapies. © 2016 New York Academy of Sciences.

Recruitment of Yoruba families from Nigeria for genetic research: experience from a multisite keloid study

PubMed Central

2014-01-01

Background More involvement of sub-Saharan African countries in biomedical studies, specifically in genetic research, is needed to advance individualized medicine that will benefit non-European populations. Missing infrastructure, cultural and religious beliefs as well as lack of understanding of research benefits can pose a challenge to recruitment. Here we describe recruitment efforts for a large genetic study requiring three-generation pedigrees within the Yoruba homelands of Nigeria. The aim of the study was to identify genes responsible for keloids, a wound healing disorder. We also discuss ethical and logistical considerations that we encountered in preparation for this research endeavor. Methods Protocols for this bi-national intercultural study were approved by the Institutional Review Board (IRB) in the US and the ethics committees of the Nigerian institutions for consideration of cultural differences. Principles of community based participatory research were employed throughout the recruitment process. Keloid patients (patient advisors), community leaders, kings/chiefs and medical directors were engaged to assist the research teams with recruitment strategies. Community meetings, church forums, and media outlets (study flyers, radio and TV announcements) were utilized to promote the study in Nigeria. Recruitment of research participants was conducted by trained staff from the local communities. Pedigree structures were re-analyzed on a regular basis as new family members were recruited and recruitment challenges were documented. Results Total recruitment surpassed 4200 study participants over a 7-year period including 79 families with complete three-generation pedigrees. In 9 families more than 20 family members participated, however, in 5 of these families, we encountered issues with pedigree structure as members from different branches presented inconsistent family histories. These issues were due to the traditional open family structure amongst the

Recruitment of Yoruba families from Nigeria for genetic research: experience from a multisite keloid study.

PubMed

Olaitan, Peter B; Odesina, Victoria; Ademola, Samuel; Fadiora, Solomon O; Oluwatosin, Odunayo M; Reichenberger, Ernst J

2014-09-02

More involvement of sub-Saharan African countries in biomedical studies, specifically in genetic research, is needed to advance individualized medicine that will benefit non-European populations. Missing infrastructure, cultural and religious beliefs as well as lack of understanding of research benefits can pose a challenge to recruitment. Here we describe recruitment efforts for a large genetic study requiring three-generation pedigrees within the Yoruba homelands of Nigeria. The aim of the study was to identify genes responsible for keloids, a wound healing disorder. We also discuss ethical and logistical considerations that we encountered in preparation for this research endeavor. Protocols for this bi-national intercultural study were approved by the Institutional Review Board (IRB) in the US and the ethics committees of the Nigerian institutions for consideration of cultural differences. Principles of community based participatory research were employed throughout the recruitment process. Keloid patients (patient advisors), community leaders, kings/chiefs and medical directors were engaged to assist the research teams with recruitment strategies. Community meetings, church forums, and media outlets (study flyers, radio and TV announcements) were utilized to promote the study in Nigeria. Recruitment of research participants was conducted by trained staff from the local communities. Pedigree structures were re-analyzed on a regular basis as new family members were recruited and recruitment challenges were documented. Total recruitment surpassed 4200 study participants over a 7-year period including 79 families with complete three-generation pedigrees. In 9 families more than 20 family members participated, however, in 5 of these families, we encountered issues with pedigree structure as members from different branches presented inconsistent family histories. These issues were due to the traditional open family structure amongst the Yoruba and by beliefs in

Kd Values for Agricultural and Surface Soils for Use in Hanford Site Farm, Residential, and River Shoreline Scenarios

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serne, R. Jeffrey

This report provides best estimate Kd values and a minimum and maximum range of Kd values to be used for agricultural soils and Columbia River bank sediments that exist today or would exist in the future when portions of the Hanford Site are released for farming, residential, and recreational use after the U. S. Department of Energy (DOE) completes clean up of defense waste on the site. The Kd values should be used to determine the fate and transport rates of contaminants and their availability for plant and animal uptake in selected non-groundwater scenarios included in Hanford Site environmental impactmore » statements, risk assessments and specific facility performance assessments. This report describes scenarios such as a small farm where drilling of a well inadvertently goes through buried waste and brings waste to the surface, allowing the tailings to become available for direct human exposure or incorporation into garden crops and farm animals used for food by the farm family. The Kd values recommended in this report can also be used to calculate sediment-water partitioning factors used to predict plant and animal uptake from interaction with the contaminated soil.« less

Exact periodic cross-kink wave solutions for the new (2+1)-dimensional KdV equation in fluid flows and plasma physics.

PubMed

Liu, Jian-Guo; Du, Jian-Qiang; Zeng, Zhi-Fang; Ai, Guo-Ping

2016-10-01

The Korteweg-de Vries (KdV)-type models have been shown to describe many important physical situations such as fluid flows, plasma physics, and solid state physics. In this paper, a new (2 + 1)-dimensional KdV equation is discussed. Based on the Hirota's bilinear form and a generalized three-wave approach, we obtain new exact solutions for the new (2 + 1)-dimensional KdV equation. With the help of symbolic computation, the properties for some new solutions are presented with some figures.

State-of-the-art acute phase management of Kawasaki disease after 2017 scientific statement from the American Heart Association.

PubMed

Liu, Yi-Ching; Lin, Ming-Tai; Wang, Jou-Kou; Wu, Mei-Hwan

2018-03-30

Kawasaki disease (KD) has become the most common form of pediatric systemic vasculitis. Although patients with KD received intravenous immunoglobulin (IVIG) therapy, coronary arterial lesions (CALs) still occurred in 5%-10% of these patients during the acute stage. CALs may persist and even progress to stenosis or obstruction. Therefore, CALs following KD are currently the leading cause of acquired heart diseases in children. The etiology of CALs remains unknown despite more than four decades of research. Two unsolved problems are IVIG unresponsiveness and the diagnosis of incomplete KD. The two subgroups of KD patients with these problems have a high risk of CAL. In April 2017, the American Heart Association (AHA) updated the guidelines for the diagnosis, treatment, and long-term management of KD. Compared with the previous KD guidelines published in 2004, the new guidelines provide solutions to the aforementioned two problems and emphasize risk stratification by using coronary artery Z score systems, as well as coronary severity-based management and long-term follow-up. Therefore, in this study, we merged the AHA Scientific Statement in 2017 with recent findings for Taiwanese KD patients to provide potential future care directions for Taiwanese patients with KD. Copyright © 2018. Published by Elsevier B.V.

Usefulness of Age-Stratified N-Terminal Prohormone of Brain Natriuretic Peptide for Diagnosing Kawasaki Disease

PubMed Central

Lee, Sang Hoon; Yoon, Somy; Hong, Seunghee; Yang, Eun Mi; Eom, Gwang Hyeon

2017-01-01

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was recently reported as a biomarker for diagnosing Kawasaki disease (KD). The basal NT-proBNP level, however, gradually decreases with age. We investigated the usefulness of an age-stratified cutoff value of NT-proBNP for diagnosing KD. All the patients enrolled in this study visited Chonnam National University Hospital between December 2007 and March 2016. The KD groups consisted of 214 patients with complete KD and 129 patients with incomplete KD. The control group included 62 children with simple febrile illness but without heart disease. Laboratory data including NT-proBNP level were evaluated. Each group was divided into subgroups according to patient age (<6 months, 6–12 months, 12–24 months, and >24 months), and different cutoff values of NT-proBNP were calculated. The cutoff values of NT-proBNP used to diagnose total KD and incomplete KD were 762 and 762 pg/mL (<6 months), 310 and 310 pg/mL (6–12 months), 326 and 326 pg/mL (12–24 months), and 208 and 137 pg/mL (>24 months), respectively. In conclusion, age-stratified NT-proBNP is a useful biomarker for the differential diagnosis of KD in patients with a simple febrile illness. PMID:29358841

Structure of the Λ (1405 ) and the K-d →π Σ n reaction

NASA Astrophysics Data System (ADS)

Ohnishi, Shota; Ikeda, Yoichi; Hyodo, Tetsuo; Weise, Wolfram

2016-02-01

The Λ (1405 ) resonance production reaction is investigated within the framework of the coupled-channels Alt-Grassberger-Sandhas (AGS) equations. We perform full three-body calculations for the K ¯N N -π Y N amplitudes on the physical real energy axis and investigate how the signature of the Λ (1405 ) appears in the cross sections of the K-d →π Σ n reactions, also in view of the planned E31 experiment at J-PARC. Two types of meson-baryon interaction models are considered: an energy-dependent interaction based on chiral S U (3 ) effective field theory, and an energy-independent version that has been used repeatedly in phenomenological approaches. These two models have different off-shell properties that imply correspondingly different behavior in the three-body system. We investigate how these features show up in differential cross sections of K-d →π Σ n reactions. Characteristic patterns distinguishing between the two models are found in the invariant mass spectrum of the final π Σ state. The K-d →π Σ n reaction, with different (π±Σ∓ and π0Σ0 ) charge combinations in the final state, is thus demonstrated to be a useful tool for investigating the subthreshold behavior of the K ¯N interaction.

Psoriasiform Eruptions During Kawasaki Disease: A Distinct Phenotype

PubMed Central

Haddock, Ellen S.; Calame, Antoanella; Shimizu, Chisato; Tremoulet, Adriana H.; Burns, Jane C.; Tom, Wynnis L.

2016-01-01

Background A psoriasis-like eruption develops in a subset of patients with Kawasaki disease (KD). Objective To systematically compare KD-associated psoriasiform eruptions with classic psoriasis and the outcomes of KD in children with and without this rash. Methods This was a retrospective study of 11 KD cases with a psoriasiform eruption matched 1:2 by age, gender, and ethnicity with psoriasis-only and KD-only controls. Genotyping was performed in 10 cases for a deletion of two late cornified envelope (LCE) genes, LCE3C_LCE3B-del, associated with increased risk for pediatric-onset psoriasis. Results Similar to classic psoriasis, KD-associated eruptions were characterized clinically by well-demarcated, scaly pink plaques and histopathologically by intraepidermal neutrophils, suprabasilar keratin 16 expression, and increased Ki-67 expression. They showed less frequent diaper area involvement, more crust and serous exudate, and an enduring remission (91% vs. 23% with confirmed resolution; p < 0.001). Frequency of LCE3C_LCE3B-del and major KD outcomes were similar between cases and controls. Limitations The study was limited by the small number of cases, treatment variation, and availability of skin biopsy specimens. Conclusions Although the overall clinical and histopathologic findings were similar to conventional psoriasis, this appears to be a distinct phenotype with significantly greater propensity for remission. No adverse effect on KD outcomes was noted. PMID:26946987

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease-Associated Abdominal Aortic Aneurysm.

PubMed

Wakita, Daiko; Kurashima, Yosuke; Crother, Timothy R; Noval Rivas, Magali; Lee, Youngho; Chen, Shuang; Fury, Wen; Bai, Yu; Wagner, Shawn; Li, Debiao; Lehman, Thomas; Fishbein, Michael C; Hoffman, Hal M; Shah, Prediman K; Shimada, Kenichi; Arditi, Moshe

2016-05-01

Kawasaki disease (KD) is the most common cause of acquired cardiac disease in US children. In addition to coronary artery abnormalities and aneurysms, it can be associated with systemic arterial aneurysms. We evaluated the development of systemic arterial dilatation and aneurysms, including abdominal aortic aneurysm (AAA) in the Lactobacillus casei cell-wall extract (LCWE)-induced KD vasculitis mouse model. We discovered that in addition to aortitis, coronary arteritis and myocarditis, the LCWE-induced KD mouse model is also associated with abdominal aorta dilatation and AAA, as well as renal and iliac artery aneurysms. AAA induced in KD mice was exclusively infrarenal, both fusiform and saccular, with intimal proliferation, myofibroblastic proliferation, break in the elastin layer, vascular smooth muscle cell loss, and inflammatory cell accumulation in the media and adventitia. Il1r(-/-), Il1a(-/-), and Il1b(-/-) mice were protected from KD associated AAA. Infiltrating CD11c(+) macrophages produced active caspase-1, and caspase-1 or NLRP3 deficiency inhibited AAA formation. Treatment with interleukin (IL)-1R antagonist (Anakinra), anti-IL-1α, or anti-IL-1β mAb blocked LCWE-induced AAA formation. Similar to clinical KD, the LCWE-induced KD vasculitis mouse model can also be accompanied by AAA formation. Both IL-1α and IL-1β play a key role, and use of an IL-1R blocking agent that inhibits both pathways may be a promising therapeutic target not only for KD coronary arteritis, but also for the other systemic arterial aneurysms including AAA that maybe seen in severe cases of KD. The LCWE-induced vasculitis model may also represent an alternative model for AAA disease. © 2016 American Heart Association, Inc.

Comparative efficacy of intralesional verapamil hydrochloride and triamcinolone acetonide in hypertrophic scars and keloids.

PubMed

Ahuja, Rajeev B; Chatterjee, Pallab

2014-06-01

There is not much level 1 evidence based literature to guide management of hypertrophic scars and keloids despite an array of therapeutic modalities at disposal. Intralesional (i/l) triamcinolone injections have remained a gold standard in non surgical management. Sporadic reports on use of i/l verapamil suggest its efficacy. Since verapamil has not found sufficient mention as an effective alternative modality, it was decided to undertake a randomized study which could also address some additional clinical parameters. A randomized, parallel group and observer blinded comparison with 40 patients (48 scars) was carried out to compare the effects of i/l triamcinolone (T) (22 scars) and verapamil injections (V) (26 scars). 1.5 ml was the maximum indicative volume decided in the study protocol for both the drugs (triamcinolone @40 mg/ml and verapamil @ 2.5 mg/ml). Patients included were aged between 15-60 years with scars ranging between 0.5-5 cm (but total area roughly <6 cm(2)), and scars under 2 years duration. Patients with keloidal diathesis were excluded. Injections were scheduled every three weeks until complete flattening of the scar or eight sessions, which ever came earlier. No concomitant therapies like massage, silicone gel or pressure garments were used. Scar evaluation at each stage was done by serial photographic records as well as by Vancouver Scar Scale (VSS). Comparative survival analysis between the two drugs was done using Kaplan Meier curves, and VSS scores were analyzed using Wilcoxon test and log rank test. Mean zero VSS scores were achieved with treatments in respect of scar height (T-12 weeks, V-21 weeks), vascularity (T-15 weeks, V-18 weeks) and pliability (T-15 weeks, V-21 weeks). The improvement in scar vascularity and pliability kept pace with decrease in scar height, in both the groups. There was not much difference in the rate of change of scar pigmentation with either drug but almost 60% patients in both the groups regained normal

Comparing Two Methods of Cryotherapy and Intense Pulsed Light with Triamcinolone Injection in the Treatment of Keloid and Hypertrophic Scars: A Clinical Trial.

PubMed

Meymandi, Simin Shamsi; Moosazadeh, Mahmood; Rezazadeh, Azadeh

2016-10-01

Keloid and hypertrophic scars are abnormal manifestations of wounds that occur following skin injuries in the form of local proliferation of fibroblasts and increased production of collagen. There are several ways to cure these scars; treatment must be selected based on the nature of the scars. In this clinical trial, two methods-cryotherapy and intense pulsed light (IPL)-are compared in the treatment of scars, and the results are presented in terms of improvement level, complications, and patient satisfaction. This clinical trial was conducted in southeastern Iran. The intervention group included scars that underwent the IPL method and the control group, which consisted of scars that were subjected to cryotherapy. In both methods, intralesional corticosteroid injection was administered. To select samples, the easy sampling method was used. To determine the expected outcomes, the criteria determined in the Vancouver scar scale were used. Data were analyzed using the Mix Model, chi-square test, and t test. In this study, 166 samples of keloid and hypertrophic scars were cured using two methods (Cryotherapy, 83; IPL, 83). The recovery rate was higher in the Cryotherapy group than in the IPL group ( p  > 0.05), and the incidence of complications was also higher in the Cryotherapy group (14.5% vs. 12%). Moreover, patients were more satisfied, although not significantly so, with the cryotherapy method ( p  = 0.09). Both methods were highly successful in curing scars; participants were totally satisfied with both methods.

On the Restricted Toda and c-KdV Flows of Neumann Type

NASA Astrophysics Data System (ADS)

Zhou, RuGuang; Qiao, ZhiJun

2000-09-01

It is proven that on a symplectic submanifold the restricted c-KdV flow is just the interpolating Hamiltonian flow of invariant for the restricted Toda flow, which is an integrable symplectic map of Neumann type. They share the common Lax matrix, dynamical r-matrix and system of involutive conserved integrals. Furthermore, the procedure of separation of variables is considered for the restricted c-KdV flow of Neumann type. The project supported by the Chinese National Basic Research Project "Nonlinear Science" and the Doctoral Programme Foundation of Institution of High Education of China. The first author also thanks the National Natural Science Foundation of China (19801031) and "Qinglan Project" of Jiangsu Province of China; and the second author also thanks the Alexander von Humboldt Fellowships, Deutschland, the Special Grant of Excellent Ph. D Thesis of China, the Science & Technology Foundation (Youth Talent Foundation) and the Science Research Foundation of Education Committee of Liaoning Province of China.

Comparative Analysis of the 15.5kD Box C/D snoRNP Core Protein in the Primitive Eukaryote Giardia lamblia Reveals Unique Structural and Functional Features

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biswas, Shyamasri; Buhrman, Greg; Gagnon, Keith

2012-07-11

Box C/D ribonucleoproteins (RNP) guide the 2'-O-methylation of targeted nucleotides in archaeal and eukaryotic rRNAs. The archaeal L7Ae and eukaryotic 15.5kD box C/D RNP core protein homologues initiate RNP assembly by recognizing kink-turn (K-turn) motifs. The crystal structure of the 15.5kD core protein from the primitive eukaryote Giardia lamblia is described here to a resolution of 1.8 {angstrom}. The Giardia 15.5kD protein exhibits the typical {alpha}-{beta}-{alpha} sandwich fold exhibited by both archaeal L7Ae and eukaryotic 15.5kD proteins. Characteristic of eukaryotic homologues, the Giardia 15.5kD protein binds the K-turn motif but not the variant K-loop motif. The highly conserved residues ofmore » loop 9, critical for RNA binding, also exhibit conformations similar to those of the human 15.5kD protein when bound to the K-turn motif. However, comparative sequence analysis indicated a distinct evolutionary position between Archaea and Eukarya. Indeed, assessment of the Giardia 15.5kD protein in denaturing experiments demonstrated an intermediate stability in protein structure when compared with that of the eukaryotic mouse 15.5kD and archaeal Methanocaldococcus jannaschii L7Ae proteins. Most notable was the ability of the Giardia 15.5kD protein to assemble in vitro a catalytically active chimeric box C/D RNP utilizing the archaeal M. jannaschii Nop56/58 and fibrillarin core proteins. In contrast, a catalytically competent chimeric RNP could not be assembled using the mouse 15.5kD protein. Collectively, these analyses suggest that the G. lamblia 15.5kD protein occupies a unique position in the evolution of this box C/D RNP core protein retaining structural and functional features characteristic of both archaeal L7Ae and higher eukaryotic 15.5kD homologues.« less

Ambient air pollution, temperature and kawasaki disease in Shanghai, China.

PubMed

Lin, Zhijing; Meng, Xia; Chen, Renjie; Huang, Guoying; Ma, Xiaojing; Chen, Jingjing; Huang, Min; Huang, Meirong; Gui, Yonghao; Chu, Chen; Liu, Fang; Kan, Haidong

2017-11-01

Kawasaki disease (KD) is a kind of pediatric vasculitis of unknown etiology which mainly affects the development of coronary artery aneurysms. Few studies have explored the potential environmental risk factors on KD incidence. We performed a time-series analysis to investigate the associations between air pollution and temperature and KD in Shanghai, China. We collected daily-hospitalized KD patients that were admitted in major pediatric specialty hospitals located in the urban areas of Shanghai from 2001 to 2010. The over-dispersed generalized additive model was used to estimate the effects of air pollutants on KD incidence on each day. Then, this model was combined with a distributed lag non-linear model to estimate the cumulative effects of temperature over a week. There were positive but statistically insignificant associations between three major air pollutants and KD incidence. The association between daily mean temperature and KD was generally J-shaped with higher risks on hot days. The cumulative relative risk of KD at extreme hot temperature (99th percentile, 32.4 °C) over a week was 1.91 [95% confidence interval (CI): 1.13, 3.23], compared with the referent temperature (10.0 °C). This study suggested that a short-term exposure to high temperature may significantly increase the incidence of KD, and the evidence linking air pollution and KD incidence was limited. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel PRNP Y218N mutation in Gerstmann-Sträussler-Scheinker disease with neurofibrillary degeneration.

PubMed

Alzualde, Ainhoa; Indakoetxea, Begoña; Ferrer, Isidre; Moreno, Fermin; Barandiaran, Myriam; Gorostidi, Ana; Estanga, Ainara; Ruiz, Irune; Calero, Miguel; van Leeuwen, Fred W; Atares, Begoña; Juste, Ramón; Rodriguez-Martínez, Ana Belén; López de Munain, Adolfo

2010-08-01

Gerstmann-Sträussler-Scheinker (GSS) disease is a prion disease associated with prion protein gene (PRNP) mutations. We report a novel PRNP mutation (Y218N) associated with GSS disease in a pathologically confirmed case and in two other affected family members. The clinical features of these cases met criteria for possible Alzheimer disease and possible frontotemporal dementia. Neuropathologic analysis revealed deposition of proteinase K-resistant prion protein (PrP(res)), widespread hyperphosphorylated tau pathology, abnormal accumulation of mitochondria in the vicinity of PrP deposits, and expression of mutant ubiquitin (UBB(+1)) in neurofibrillary tangles and dystrophic neurites. Prion protein immunoblotting using 3F4 and 1E4 antibodies disclosed multiple bands ranging from approximately 20 kd to 80 kd and lower bands of 15 kd and approximately 10 kd, the latter only seen after a long incubation. These bands were partially resistant to proteinase K pretreatment. This pattern differs from those seen in Creutzfeldt-Jakob disease andresembles those reported in other GSS cases. The approximately 10kd band was recognized with anti-PrP C-terminus antibodies but not with anti-N terminus antibodies, suggesting PrP truncation at the N terminal. This new mutation extends the list of known mutations responsible for GSS disease and reinforces its clinical heterogeneity. Genetic examination of the PRNP gene should be included in the workup of patients with poorly classifiable dementia.

Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.

PubMed

Chang, Chia-Jung; Kuo, Ho-Chang; Chang, Jeng-Sheng; Lee, Jong-Keuk; Tsai, Fuu-Jen; Khor, Chiea Chuen; Chang, Li-Ching; Chen, Shih-Ping; Ko, Tai-Ming; Liu, Yi-Min; Chen, Ying-Ju; Hong, Young Mi; Jang, Gi Young; Hibberd, Martin L; Kuijpers, Taco; Burgner, David; Levin, Michael; Burns, Jane C; Davila, Sonia; Chen, Yuan-Tsong; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Lee, Yi-Ching

2013-01-01

The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD ) comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls) providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354-1.657; P = 4.74×10(-31)). We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC) population and the expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD.

Exact PsTd invariant and PsTd symmetric breaking solutions, symmetry reductions and Bäcklund transformations for an AB-KdV system

NASA Astrophysics Data System (ADS)

Jia, Man; Lou, Sen Yue

2018-05-01

In natural and social science, many events happened at different space-times may be closely correlated. Two events, A (Alice) and B (Bob) are defined as correlated if one event is determined by another, say, B = f ˆ A for suitable f ˆ operators. A nonlocal AB-KdV system with shifted-parity (Ps, parity with a shift), delayed time reversal (Td, time reversal with a delay) symmetry where B =Ps ˆ Td ˆ A is constructed directly from the normal KdV equation to describe two-area physical event. The exact solutions of the AB-KdV system, including PsTd invariant and PsTd symmetric breaking solutions are shown by different methods. The PsTd invariant solution show that the event happened at A will happen also at B. These solutions, such as single soliton solutions, infinitely many singular soliton solutions, soliton-cnoidal wave interaction solutions, and symmetry reduction solutions etc., show the AB-KdV system possesses rich structures. Also, a special Bäcklund transformation related to residual symmetry is presented via the localization of the residual symmetry to find interaction solutions between the solitons and other types of the AB-KdV system.

Lie symmetry analysis, conservation laws and exact solutions of the time-fractional generalized Hirota-Satsuma coupled KdV system

NASA Astrophysics Data System (ADS)

Saberi, Elaheh; Reza Hejazi, S.

2018-02-01

In the present paper, Lie point symmetries of the time-fractional generalized Hirota-Satsuma coupled KdV (HS-cKdV) system based on the Riemann-Liouville derivative are obtained. Using the derived Lie point symmetries, we obtain similarity reductions and conservation laws of the considered system. Finally, some analytic solutions are furnished by means of the invariant subspace method in the Caputo sense.

Primary Coenzyme Q Deficiency in Pdss2 Mutant Mice Causes Isolated Renal Disease

PubMed Central

Haase, Volker H.; King, Rhonda; Polyak, Erzsebet; Selak, Mary; Yudkoff, Marc; Hancock, Wayne W.; Meade, Ray; Saiki, Ryoichi; Lunceford, Adam L.; Clarke, Catherine F.; Gasser, David L.

2008-01-01

Coenzyme Q (CoQ) is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 deficiency. We now show that a presumed autoimmune kidney disease in mice with the missense Pdss2kd/kd genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2kd/kd mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2loxP/loxP knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Liver-conditional B6.Alb/cre,Pdss2loxP/loxP knockout mice have no overt disease despite demonstration that their livers have undetectable CoQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism as evidenced by transcriptional profiling and amino acid quantitation. These data suggest that disease manifestations of CoQ deficiency relate to tissue-specific respiratory capacity thresholds, with glomerular podocytes displaying the greatest sensitivity to Pdss2 impairment. PMID:18437205

An outline of cellular automaton universe via cosmological KdV equation

NASA Astrophysics Data System (ADS)

Christianto, V.; Smarandache, F.; Umniyati, Y.

2018-03-01

It has been known for long time that the cosmic sound wave was there since the early epoch of the Universe. Signatures of its existence are abound. However, such a sound wave model of cosmology is rarely developed fully into a complete framework. This paper can be considered as our second attempt towards such a complete description of the Universe based on soliton wave solution of cosmological KdV equation. Then we advance further this KdV equation by virtue of Cellular Automaton method to solve the PDEs. We submit wholeheartedly Robert Kuruczs hypothesis that Big Bang should be replaced with a finite cellular automaton universe with no expansion [4][5]. Nonetheless, we are fully aware that our model is far from being complete, but it appears the proposed cellular automaton model of the Universe is very close in spirit to what Konrad Zuse envisaged long time ago. It is our hope that the new proposed method can be verified with observation data. But we admit that our model is still in its infancy, more researches are needed to fill all the missing details.

Purification and partial characterization ofa 67-kD cross-react ive allergen from Imperata cylindrica pollen extract.

PubMed

Verma, J; Singh, B P; Gangal, S V; Arora, N; Sridhara, S

2000-08-01

Grass pollens are known to induce type I allergic reactions in a large number of genetically predisposed individuals. Earlier studies have recognized Imperata cylindrica (Ic) pollen as an important source of aeroallergen which contained 7 IgE binding proteins in the MW range of 85-16 kD. To isolate, purify and characterize a cross-reactive allergenic protein from Ic pollen extract for diagnosis and therapy of grass pollen allergy. Ic pollen extract was fractionated using DEAE Sephadex A-50, Sephadex G-200 and Mono Q column. Allergenic activity of the fractions was checked by ELISA, skin tests, ELISA inhibition and immunoblot using sera of Ic-sensitive patients. A 67-kD protein was purified to homogeneity from Ic-VIII. The allergenic determinants of this protein were identified by SDS-PAGE and immunoblot after CNBr treatment. Among Ic fractions, Ic-VIII was highly potent by ELISA, skin tests and showed cross-reactivity with 4 other tropical grasses by immunoblot and ELISA inhibition. The subfraction Ic-VIIIe1 of Ic-VIII showed a band at 67 kD on SDS-PAGE. On CNBr treatment, it gave 7 peptides, 3 of which were found to be allergenic. A 67-kD protein (Ic-VIIIe1) was isolated, purified to homogeneity and partially characterized. It showed cross-reactivity with tropical grasses tested and contained at least three allergenic determinants. Copyright 2000 S. Karger AG, Basel.

Dynamic Load Balancing Based on Constrained K-D Tree Decomposition for Parallel Particle Tracing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jiang; Guo, Hanqi; Yuan, Xiaoru

Particle tracing is a fundamental technique in flow field data visualization. In this work, we present a novel dynamic load balancing method for parallel particle tracing. Specifically, we employ a constrained k-d tree decomposition approach to dynamically redistribute tasks among processes. Each process is initially assigned a regularly partitioned block along with duplicated ghost layer under the memory limit. During particle tracing, the k-d tree decomposition is dynamically performed by constraining the cutting planes in the overlap range of duplicated data. This ensures that each process is reassigned particles as even as possible, and on the other hand the newmore » assigned particles for a process always locate in its block. Result shows good load balance and high efficiency of our method.« less

Ethnic Kawasaki Disease Risk Associated with Blood Mercury and Cadmium in U.S. Children

PubMed Central

Yeter, Deniz; Portman, Michael A.; Aschner, Michael; Farina, Marcelo; Chan, Wen-Ching; Hsieh, Kai-Sheng; Kuo, Ho-Chang

2016-01-01

Kawasaki disease (KD) primarily affects children <5 years of age (75%–80%) and is currently the leading cause of acquired heart disease in developed nations. Even when residing in the West, East Asian children are 10 to 20 times more likely to develop KD. We hypothesized cultural variations influencing pediatric mercury (Hg) exposure from seafood consumption may mediate ethnic KD risk among children in the United States. Hospitalization rates of KD in US children aged 0–4 years (n = 10,880) and blood Hg levels in US children aged 1–5 years (n = 713) were determined using separate US federal datasets. Our cohort primarily presented with blood Hg levels <0.1 micrograms (µg) per kg bodyweight (96.5%) that are considered normal and subtoxic. Increased ethnic KD risk was significantly associated with both increasing levels and detection rates of blood Hg or cadmium (Cd) in a linear dose-responsive manner between ethnic African, Asian, Caucasian, and Hispanic children in the US (p ≤ 0.05). Increasing low-dose exposure to Hg or Cd may induce KD or contribute to its later development in susceptible children. However, our preliminary results require further replication in other ethnic populations, in addition to more in-depth examination of metal exposure and toxicokinetics. PMID:26742052

Analysis of the internal nuclear matrix. Oligomers of a 38 kD nucleolar polypeptide stabilized by disulfide bonds.

PubMed

Fields, A P; Kaufmann, S H; Shaper, J H

1986-05-01

When rat liver nuclei are treated with the sulfhydryl cross-linking reagent sodium tetrathionate (NaTT) prior to nuclease treatment and extraction with 1.6 M NaCl, residual nucleoli and an extensive non-chromatin intranuclear network remain associated with the nuclear envelope. Subsequent treatment of this structure with 1 M NaCl containing 20 mM dithiothreitol (DTT) solubilizes the intranuclear material, while the nuclear envelope remains structurally intact. We have isolated and partially characterized a major polypeptide of the disulfide-stabilized internal nuclear matrix. The polypeptide, which has an apparent molecular mass 38 kD and isoelectric point 5.3, has been localized to the nucleolus of rat liver nuclei by indirect immunofluorescence using a specific polyclonal chicken antiserum. Based on its molecular mass, isoelectric point, intracellular localization and amino acid composition, the 38 kD polypeptide appears to be analogous to the nucleolar phosphoprotein B23 described by Prestayko et al. (Biochemistry 13 (1974) 1945) [20]. Immunologically related polypeptides have likewise been localized to the nucleoli of both hamster and human tissue culture cell lines as well as the cellular slime mold Physarum polycephalum. By immunoblotting, a single 38 kD polypeptide is recognized by the antiserum in rat, mouse, hamster and human cell lines. The antiserum has been utilized to investigate the oligomeric structure of the 38 kD polypeptide and the nature of its association with the rat liver nuclear matrix. By introducing varying numbers of disulfide bonds, we have found that the 38 kD polypeptide becomes incorporated into the internal nuclear matrix in a two-step process. Soluble disulfide-bonded homodimers of the polypeptide are first formed and then are rendered salt-insoluble by more extensive disulfide cross-linking.

REVISED GUIDELINES FOR USING CELLULOSE DEGRADATION PRODUCT-IMPACTED KD VALUES FOR PERFORMANCE ASSESSMENTS AND COMPOSITE ANALYSES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaplan, D.

2012-05-14

Cellulosic materials include wood, paper, rags, and cardboard products. These materials are co-disposed with radiological waste at the Savannah River Site's (SRS) E-Area Low-Level Waste Facility (ELLWF). Cellulosic materials readily degrade in the environment to form cellulose degradation products (CDP) that will partition to the sediment or remain mobile in the groundwater. Savannah River National Lab (SRNL) has conducted studies to estimate the impact of CDP on radionuclide sorption to SRS sediments (Kd values). It was found that CDP impact on radionuclide sorption varies with radionuclide and CDP concentration. Furthermore, it was found that the amount of carbon (C) inmore » the system could increase or decrease Kd values with respect to the base case of when no CDP was added. Throughout the expected pH range of the ELLWF, a low concentration of CDP in the system would increase Kd values (because C would sorb to the sediment and provide more exchange sites for radionuclides to sorb), whereas greater concentrations of CDP ({ge}20 mg/L C) would decrease Kd values (because C would remain in solution and complex the radionuclide and not permit the radionuclide to sorb to the sediment). A review of >230 dissolved organic carbon (DOC) groundwater concentrations in the Old Radioactive Waste Burial Ground (ORWBG) at the SRS indicated that the average DOC concentration, a gross measure of CDP, was 5 mg/L C. At approximately this DOC concentration, the laboratory studies demonstrated that no anions (Tc, I, or Se) or cations (Ni, Sr, Ce, Eu, Zr, or Th) have decreased sorption in the presence of carbon (an analogue for CDP).« less

Genetic variants of CD209 associated with Kawasaki disease susceptibility.

PubMed

Kuo, Ho-Chang; Huang, Ying-Hsien; Chien, Shu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Chang, Wei-Chiao

2014-01-01

Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD. A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses. CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness.

CD8+ T Cells Contribute to the Development of Coronary Arteritis in the Lactobacillus casei Cell Wall Extract-Induced Murine Model of Kawasaki Disease.

PubMed

Noval Rivas, Magali; Lee, Youngho; Wakita, Daiko; Chiba, Norika; Dagvadorj, Jargalsaikhan; Shimada, Kenichi; Chen, Shuang; Fishbein, Michael C; Lehman, Thomas J A; Crother, Timothy R; Arditi, Moshe

2017-02-01

Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries. Coronary lesions in KD in humans are characterized by an increased presence of infiltrating CD3+ T cells; however, the specific contributions of the different T cell subpopulations in coronary arteritis development remain unknown. Therefore, we sought to investigate the function of CD4+ and CD8+ T cells, Treg cells, and natural killer (NK) T cells in the pathogenesis of KD. We addressed the function of T cell subsets in KD development by using a well-established murine model of Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis. We determined which T cell subsets were required for development of KD vasculitis by using several knockout murine strains and depleting monoclonal antibodies. LCWE-injected mice developed coronary lesions characterized by the presence of inflammatory cell infiltrates. Frequently, this chronic inflammation resulted in complete occlusion of the coronary arteries due to luminal myofibroblast proliferation (LMP) as well as the development of coronary arteritis and aortitis. We found that CD8+ T cells, but not CD4+ T cells, NK T cells, or Treg cells, were required for development of KD vasculitis. The LCWE-induced murine model of KD vasculitis mimics many histologic features of the disease in humans, such as the presence of CD8+ T cells and LMP in coronary artery lesions as well as epicardial coronary arteritis. Moreover, CD8+ T cells functionally contribute to the development of KD vasculitis in this murine model. Therapeutic strategies targeting infiltrating CD8+ T cells might be useful in the management of KD in humans. © 2016, American College of Rheumatology.

Nonlinear waves of a nonlocal modified KdV equation in the atmospheric and oceanic dynamical system

NASA Astrophysics Data System (ADS)

Tang, Xiao-yan; Liang, Zu-feng; Hao, Xia-zhi

2018-07-01

A new general nonlocal modified KdV equation is derived from the nonlinear inviscid dissipative and equivalent barotropic vorticity equation in a β-plane. The nonlocal property is manifested in the shifted parity and delayed time reversal symmetries. Exact solutions of the nonlocal modified KdV equation are obtained including periodic waves, kink waves, solitary waves, kink- and/or anti-kink-cnoidal periodic wave interaction solutions, which can be utilized to describe various two-place and time-delayed correlated events. As an illustration, a special approximate solution is applied to theoretically capture the salient features of two correlated dipole blocking events in atmospheric dynamical systems.

miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition: Therapeutic Implications in Kawasaki Disease

PubMed Central

He, Ming; Chen, Zhen; Martin, Marcy; Zhang, Jin; Sangwung, Panjamaporn; Woo, Brian; Tremoulet, Adriana H.; Shimizu, Chisato; Jain, Mukesh K.; Burns, Jane C.; Shyy, John Y-J.

2016-01-01

Rationale Endothelial-to-mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell-mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD. Objective We investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis. As well, the modulation of this process by statin therapy was studied. Methods and Results Sera from healthy children and KD subjects were incubated with human umbilical vein endothelial cells (HUVECs). Cardiovascular disease-related miRNAs, CTGF, and EndoMT markers were quantified using RT-qPCR, ELISA, and Western blotting. Compared to healthy controls, HUVEC incubated with sera from acute KD patients had decreased miR-483, increased CTGF, and increased EndoMT markers. Bioinformatics analysis followed by functional validation demonstrated that Krüppel-like factor 4 (KLF4) transactivates miR-483, which in turn targets the 3′ untranslated region of CTGF mRNA. Overexpression of KLF4 or pre-miR-483 suppressed, whereas knockdown of KLF4 or anti-miR-483 enhanced, CTGF expression in ECs in vitro and in vivo. Furthermore, atorvastatin, currently being tested in a Phase I/IIa clinical trial in KD children, induced KLF4-miR-483, which suppressed CTGF and EndoMT in ECs. Conclusions KD sera suppress the KLF4-miR-483 axis in ECs leading to increased expression of CTGF and induction of EndoMT. This detrimental process in the endothelium may contribute to coronary artery abnormalities in KD patients. Statin therapy may benefit acute KD patients, in part through the restoration of KLF4-miR-483 expression. Clinical Trial Registration NCT01431105 PMID:27923814

Atrioventricular depolarization differences identify coronary artery anomalies in Kawasaki disease.

PubMed

Cortez, Daniel; Sharma, Nandita; Jone, Pei-Ni

2017-03-01

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. Signal average electrocardiogram changes in patients during the acute phase of KD with coronary artery anomalies (CAA) include depolarization changes. We set out to determine if 12-lead-derived atrioventricular depolarization differences can identify CAA in patients with KD. A blinded, retrospective case-control study of patients with KD was performed. Deep Q waves, corrected QT-intervals (QTc), spatial QRS-T angles, T-wave vector magnitudes (RMS-T), and a novel parameter for assessment of atrioventricular depolarization difference (the spatial PR angle) and a two dimensional PR angle were assessed. Comparisons between groups were performed to test for significant differences. One hundred one patients with KD were evaluated, with 68 having CAA (67.3%, mean age 3.6 ± 3.0 years, 82.6% male), and 32 without CAA (31.7%, mean age 2.7 ± 3.2 years, 70.4% male). The spatial PR angle significantly discriminated KD patients with CAA from those without, 59.7° ± 31.1° versus 41.6° ± 11.5° (p < .001). A spatial PR angle cutoff value of 56.9° gave positive/negative predictive values and odds ratios of 93.8%, 43.5%, and 11.5% (95% confidence interval (CI) 2.6-52.2). The two dimensional PR angle either below 7° or above 92° gave positive/negative predictive values and odds ratios of 100.0%, 38.8%, and 21.1% (95% CI 1.2-362.8). No other parameters significantly differentiated the groups. Atrioventricular depolarization differences, measured by the spatial or two dimensional PR angle differentiate KD patients with CAA versus those without. © 2016 Wiley Periodicals, Inc.

K-Means Algorithm Performance Analysis With Determining The Value Of Starting Centroid With Random And KD-Tree Method

NASA Astrophysics Data System (ADS)

Sirait, Kamson; Tulus; Budhiarti Nababan, Erna

2017-12-01

Clustering methods that have high accuracy and time efficiency are necessary for the filtering process. One method that has been known and applied in clustering is K-Means Clustering. In its application, the determination of the begining value of the cluster center greatly affects the results of the K-Means algorithm. This research discusses the results of K-Means Clustering with starting centroid determination with a random and KD-Tree method. The initial determination of random centroid on the data set of 1000 student academic data to classify the potentially dropout has a sse value of 952972 for the quality variable and 232.48 for the GPA, whereas the initial centroid determination by KD-Tree has a sse value of 504302 for the quality variable and 214,37 for the GPA variable. The smaller sse values indicate that the result of K-Means Clustering with initial KD-Tree centroid selection have better accuracy than K-Means Clustering method with random initial centorid selection.

Cardiac Complications in 38 Cases of Kawasaki Disease with Coronary Artery Aneurysm Diagnosed by Echocardiography.

PubMed

Wei, Ya Juan; Zhao, Xiao Lan; Liu, Bao Min; Niu, Hua; Li, Qian

2016-05-01

The long-term prognosis of patients with Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA) is unclear. The aim of this study was to evaluate the complications of KD with CAAs. We retrospectively analyzed the clinical data and complications of 38 KD patients with CAAs who were treated and underwent regular follow-up with echocardiography between January 1989 and May 2013. During a period of 29 days to 19 years after disease onset, complications seen included coronary stenosis and occlusion (six patients), thrombosis (17 patients), myocardial infarction (six patients), and calcification of CAAs (seven patients). Rupture of giant CAAs occurred in two patients and caused sudden death in one of these patients at 29 days and in the other patient at 5 months after disease onset. A total of seven deaths occurred, with five deaths caused by myocardial infarction. Three of these had undiagnosed incomplete KD or had not received regular treatment, while two experienced sudden death after several asymptomatic myocardial infarctions. Cardiac complications of KD with CAAs include thrombosis, coronary stenosis, myocardial infarction, sudden death, and calcification. Although rare, rupture of giant CAAs is fatal and might occur earlier after the onset of disease. Mortality occurred primarily in the earlier cases when anticoagulant therapy was insufficient and in patients who did not receive regular treatment. Echocardiography can provide reliable information for assessing the progression and prognosis of this condition. © 2015, Wiley Periodicals, Inc.

Retrieval of the spectral diffuse attenuation coefficient Kd(λ) in open and coastal ocean waters using a neural network inversion

NASA Astrophysics Data System (ADS)

Jamet, C.; Loisel, H.; Dessailly, D.

2012-10-01

The diffuse attenuation coefficient, Kd(λ) is a fundamental radiometric parameter that is used to assess the light availability in the water column. A neural network approach is developed to assess Kd(λ) at any visible wavelengths from the remote sensing reflectances as measured by the SeaWiFS satellite sensor. The neural network (NN) inversion is trained using a combination of simulated and in-situ data sets covering a broad range ofKd(λ), between 0.0073 m-1 at 412 nm and 12.41 m-1at 510 nm. The performance of the retrieval is evaluated against two data sets, one consisting of mainly synthetic data while the other one contains in-situ data only and is compared to those obtained with previous published empirical (NASA, Morel and Maritorena (2001) and Zhang and Fell (2007)) and semi-analytical (Lee et al., 2005b) algorithms. On the in-situ data set from the COASTLOOC campaign, the retrieval accuracy of the present algorithm is quite similar to published algorithms for oligotrophic and mesotrophic ocean waters. But for Kd(490) > 0.25 m-1, the NN approach allows to retrieve Kd(490) with a much better accuracy than the four other methods. The results are consistent when compared with other SeaWiFS wavelengths. This new inversion is as suitable in the open ocean waters as in the turbid waters. The work here is straightforwardly applicable to the MERIS sensor and with few changes to the MODIS-AQUA sensor. The algorithm in matlab and C code is provided as auxiliary material.

The 87-kD A gamma-globin enhancer-binding protein is a product of the HOXB2(HOX2H) locus.

PubMed

Sengupta, P K; Lavelle, D E; DeSimone, J

1994-03-01

Developmental regulation of globin gene expression may be controlled by developmental stage-specific nuclear proteins that influence interactions between the locus control region and local regulatory sequences near individual globin genes. We previously isolated an 87-kD nuclear protein from K562 cells that bound to DNA sequences in the beta-globin locus control region, gamma-globin promoter, and A gamma-globin enhancer. The presence of this protein in fetal globin-expressing cells and its absence in adult globin-expressing cells suggested that it may be a developmental stage-specific factor. A lambda gt11 K562 cDNA clone encoding a portion of the HOXB2 (formerly HOX2H) homeobox gene was isolated on the basis of the ability of its beta-galactosidase fusion protein to bind to the same DNA sequences as the 87-kD K562 protein. Because no other relationship had been established between the 87-kD K562 protein and the HOXB2 protein other than their ability to bind ot the same DNA sequences, we have investigated whether the two proteins are related antigenically. Our data show that antisera produced against the HOXB2-beta-gal fusion protein and a synthetic HOXB2 decapeptide react specifically with an 87-kD protein from K562 nuclear extract, showing that the 87-kD K562 nuclear protein is a product of the HOXB2 locus, and is the first demonstration of cellular HOXB2 protein.

Cardiopulmonary Function, Exercise Capacity, and Echocardiography Finding of Pediatric Patients With Kawasaki Disease

PubMed Central

Tuan, Sheng-Hui; Li, Min-Hui; Hsu, Miao-Ju; Tsai, Yun-Jeng; Chen, Yin-Han; Liao, Tin-Yun; Lin, Ko-Long

2016-01-01

Abstract Coronary artery (CA) abnormalities influence exercise capacity (EC) of patients with Kawasaki disease (KD), and Z-score of CA is a well established method for detecting CA aneurysm. We studied the influence of KD on cardiopulmonary function and EC; meanwhile we analyzed echocardiographic findings of KD patients. We also assessed the correlation between CA Z-score and EC of KD patients to see if CA Z-score of KD patients could reflect EC during exercise. Sixty-three KD patients were recruited as KD group 1 from children (aged 5–18 y) who received transthoracic echocardiographic examinations and symptom-limited treadmill exercise test for regular follow-up of KD from January 2010 to October 2014 in 1 medical center. We then divided KD group 1 into KD group 2 (<5 y, n = 12) and KD group 3 (≥5 y, n = 51) according to time interval between KD onset to when patients received test. Control groups were matched by age, sex, and body mass index. Max-Z of CA was defined as the maximal Z-score of the proximal LCA or RCA by Dalliarre equation or Fuse calculator. All routine parameters measured during standard exercise test were similar between KD and control groups, except that peak rate pressure products (PRPPs) in KD group 1 to 3 were all lower than corresponding control groups significantly (P = 0.010, 0.020, and 0.049, respectively). PRPPs correlated with Max-Z of CA by both equations modest inversely (by Dallaire, P = 0.017, Spearman rho = −0.301; by Fuse, P = 0.014, Spearman rho = −0.309). Our study recruited larger number of KD patients and provided a newer data of EC of KD patients. Our finding suggests that after acute stage of KD, patients could maintain normal cardiorespiratory fitness. Therefore, we believe that it is important to promote cardiovascular health to KD patients and KD patients should exercise as normal peers. However, since KD patients might still have compromised coronary perfusion during exercise, it

Levels of intra- and extracellular heat shock protein 60 in Kawasaki disease patients treated with intravenous immunoglobulin.

PubMed

Yin Ji, Xu; Kang, Mi-Ran; Choi, Jong-Sung; Jeon, Hak-Soo; Han, Heon-Seok; Kim, Ji-Yoon; Son, Bo-Ra; Lee, Young-Min; Hahn, Youn-Soo

2007-09-01

Immune reactivity to autologous heat shock protein 60 (HSP60) has been reported to be associated with a favorable prognosis in autoimmune diseases. To provide a clue for the possible role of HSP60 in Kawasaki disease (KD), we investigated the levels of intra- and extracellular HSP60 in the course of KD. In KD patients, autologous HSP60 was abundantly expressed in CD11c(+) cells during the acute phase and subsequently decreased during the subacute phase. Most of HSP60-expressing CD11c(+) cells observed in the acute phase was composed of CD11c(low) cells instead of CD11c(high) cells, which were dominant in the subacute phase. In contrast, circulating HSP60 levels were higher in the subacute phase than those in the acute phase, reflecting higher level of HSP60 exposure to the immune system of patients during recovery. These changes in the levels of intra- and extracellular HSP60 were not observed in patients with other febrile diseases. The observed features of HSP60 expression in patients with KD are in favor of a role for autologous HSP60 as a regulator for control of inflammation, rather than a proinflammatory mediator in KD.

Exact solutions for STO and (3+1)-dimensional KdV-ZK equations using (G‧/G2) -expansion method

NASA Astrophysics Data System (ADS)

Bibi, Sadaf; Mohyud-Din, Syed Tauseef; Ullah, Rahmat; Ahmed, Naveed; Khan, Umar

This article deals with finding some exact solutions of nonlinear fractional differential equations (NLFDEs) by applying a relatively new method known as (G‧/G2) -expansion method. Solutions of space-time fractional Sharma-Tasso-Olever (STO) equation of fractional order and (3+1)-dimensional KdV-Zakharov Kuznetsov (KdV-ZK) equation of fractional order are reckoned to demonstrate the validity of this method. The fractional derivative version of modified Riemann-Liouville, linked with Fractional complex transform is employed to transform fractional differential equations into the corresponding ordinary differential equations.

Genetic Variants of CD209 Associated with Kawasaki Disease Susceptibility

PubMed Central

Kuo, Ho-Chang; Huang, Ying-Hsien; Chien, Shu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Chang, Wei-Chiao

2014-01-01

Background Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD. Methods A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Results Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses. Conclusion CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness. PMID:25148534

Amyloid tracers detect multiple binding sites in Alzheimer's disease brain tissue.

PubMed

Ni, Ruiqing; Gillberg, Per-Göran; Bergfors, Assar; Marutle, Amelia; Nordberg, Agneta

2013-07-01

Imaging fibrillar amyloid-β deposition in the human brain in vivo by positron emission tomography has improved our understanding of the time course of amyloid-β pathology in Alzheimer's disease. The most widely used amyloid-β imaging tracer so far is (11)C-Pittsburgh compound B, a thioflavin derivative but other (11)C- and (18)F-labelled amyloid-β tracers have been studied in patients with Alzheimer's disease and cognitively normal control subjects. However, it has not yet been established whether different amyloid tracers bind to identical sites on amyloid-β fibrils, offering the same ability to detect the regional amyloid-β burden in the brains. In this study, we characterized (3)H-Pittsburgh compound B binding in autopsied brain regions from 23 patients with Alzheimer's disease and 20 control subjects (aged 50 to 88 years). The binding properties of the amyloid tracers FDDNP, AV-45, AV-1 and BF-227 were also compared with those of (3)H-Pittsburgh compound B in the frontal cortices of patients with Alzheimer's disease. Saturation binding studies revealed the presence of high- and low-affinity (3)H-Pittsburgh compound B binding sites in the frontal cortex (K(d1): 3.5 ± 1.6 nM; K(d2): 133 ± 30 nM) and hippocampus (K(d1):5.6 ± 2.2 nM; K(d2): 181 ± 132 nM) of Alzheimer's disease brains. The relative proportion of high-affinity to low-affinity sites was 6:1 in the frontal cortex and 3:1 in the hippocampus. One control showed both high- and low-affinity (3)H-Pittsburgh compound B binding sites (K(d1): 1.6 nM; K(d2): 330 nM) in the cortex while the others only had a low-affinity site (K(d2): 191 ± 70 nM). (3)H-Pittsburgh compound B binding in Alzheimer's disease brains was higher in the frontal and parietal cortices than in the caudate nucleus and hippocampus, and negligible in the cerebellum. Competitive binding studies with (3)H-Pittsburgh compound B in the frontal cortices of Alzheimer's disease brains revealed high- and low-affinity binding sites for BTA

Estimating the Underwater Diffuse Attenuation Coefficient with a Low-Cost Instrument: The KdUINO DIY Buoy.

PubMed

Bardaji, Raul; Sánchez, Albert-Miquel; Simon, Carine; Wernand, Marcel R; Piera, Jaume

2016-03-15

A critical parameter to assess the environmental status of water bodies is the transparency of the water, as it is strongly affected by different water quality related components (such as the presence of phytoplankton, organic matter and sediment concentrations). One parameter to assess the water transparency is the diffuse attenuation coefficient. However, the number of subsurface irradiance measurements obtained with conventional instrumentation is relatively low, due to instrument costs and the logistic requirements to provide regular and autonomous observations. In recent years, the citizen science concept has increased the number of environmental observations, both in time and space. The recent technological advances in embedded systems and sensors also enable volunteers (citizens) to create their own devices (known as Do-It-Yourself or DIY technologies). In this paper, a DIY instrument to measure irradiance at different depths and automatically calculate the diffuse attenuation Kd coefficient is presented. The instrument, named KdUINO, is based on an encapsulated low-cost photonic sensor and Arduino (an open-hardware platform for the data acquisition). The whole instrument has been successfully operated and the data validated comparing the KdUINO measurements with the commercial instruments. Workshops have been organized with high school students to validate its feasibility.

Estimating the Underwater Diffuse Attenuation Coefficient with a Low-Cost Instrument: The KdUINO DIY Buoy

PubMed Central

Bardaji, Raul; Sánchez, Albert-Miquel; Simon, Carine; Wernand, Marcel R.; Piera, Jaume

2016-01-01

A critical parameter to assess the environmental status of water bodies is the transparency of the water, as it is strongly affected by different water quality related components (such as the presence of phytoplankton, organic matter and sediment concentrations). One parameter to assess the water transparency is the diffuse attenuation coefficient. However, the number of subsurface irradiance measurements obtained with conventional instrumentation is relatively low, due to instrument costs and the logistic requirements to provide regular and autonomous observations. In recent years, the citizen science concept has increased the number of environmental observations, both in time and space. The recent technological advances in embedded systems and sensors also enable volunteers (citizens) to create their own devices (known as Do-It-Yourself or DIY technologies). In this paper, a DIY instrument to measure irradiance at different depths and automatically calculate the diffuse attenuation Kd coefficient is presented. The instrument, named KdUINO, is based on an encapsulated low-cost photonic sensor and Arduino (an open-hardware platform for the data acquisition). The whole instrument has been successfully operated and the data validated comparing the KdUINO measurements with the commercial instruments. Workshops have been organized with high school students to validate its feasibility. PMID:26999132

Remote sensing observation of annual dust cycles and possible causality of Kawasaki disease outbreaks in Japan

PubMed Central

LaHaye, Nick; Linstead, Erik; Sprigg, William A.; Yacoub, Magdi

Kawasaki disease (KD) is a rare vascular disease that, if left untreated, can result in irreparable cardiac damage in children. While the symptoms of KD are well-known, as are best practices for treatment, the etiology of the disease and the factors contributing to KD outbreaks remain puzzling to both medical practitioners and scientists alike. Recently, a fungus known as Candida, originating in the farmlands of China, has been blamed for outbreaks in China and Japan, with the hypothesis that it can be transported over long ranges via different wind mechanisms. This paper provides evidence to understand the transport mechanisms of dust at different geographic locations and the cause of the annual spike of KD in Japan. Candida is carried along with many other dusts, particles or aerosols, of various sizes in major seasonal wind currents. The evidence is based upon particle categorization using the Moderate Resolution Imaging Spectrometer (MODIS) Aerosol Optical Depth (AOD), Fine Mode Fraction (FMF) and Ångström Exponent (AE), the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) attenuated backscatter and aerosol subtype, and the Aerosol Robotic Network’s (AERONET) derived volume concentration. We found that seasonality associated with aerosol size distribution at different geographic locations plays a role in identifying dominant abundance at each location. Knowing the typical size of the Candida fungus, and analyzing aerosol characteristics using AERONET data reveals possible particle transport association with KD events at different locations. Thus, understanding transport mechanisms and accurate identification of aerosol sources is important in order to understand possible triggers to outbreaks of KD. This work provides future opportunities to leverage machine learning, including state-of-the-art deep architectures, to build predictive models of KD outbreaks, with the ultimate goal of early forecasting and intervention within a

Blow-up solutions for L 2 supercritical gKdV equations with exactly k blow-up points

NASA Astrophysics Data System (ADS)

Lan, Yang

2017-08-01

In this paper we consider the slightly L 2-supercritical gKdV equations \\partialt u+(uxx+u\\vert u\\vert p-1)_x=0 , with the nonlinearity 5 and 0<\\varepsilon\\ll 1 . In the previous work of the author, we know that there exists a stable self-similar blow-up dynamics for slightly L 2-supercritical gKdV equations. Such solutions can be viewed as solutions with a single blow-up point. In this paper we will prove the existence of solutions with multiple blow-up points, and give a description of the formation of the singularity near the blow-up time.

Determination of solid-liquid partition coefficients (Kd) for the herbicides isoproturon and trifluralin in five UK agricultural soils.

PubMed

Cooke, Cindy M; Shaw, George; Collins, Chris D

2004-12-01

Isoproturon and trifluralin are herbicides of contrasting chemical characters and modes of action. Standard batch sorption procedures were carried out to investigate the individual sorption behaviour of 14C-isoproturon and 14C-trifluralin in five agricultural soils (1.8-4.2% OC), and the soil solid-liquid partition coefficients (Kd values) were determined. Trifluralin exhibited strong partitioning to the soil solid phase (Kd range 106-294) and low desorption potential, thus should not pose a threat to sensitive waters via leaching, although particle erosion and preferential flow pathways may facilitate transport. For isoproturon, soil adsorption was low (Kd range 1.96-5.75) and desorption was high, suggesting a high leaching potential, consistent with isoproturon being the most frequently found pesticide in UK surface waters. Soil partitioning was directly related to soil organic carbon (OC) content. Accumulation isotherms were modelled using a dual-phase adsorption model to estimate adsorption and desorption rate coefficients. Associations between herbicides and soil humic substances were also shown using gel filtration chromatography.

Epidemiologic Features of Kawasaki Disease in Shanghai From 2008 Through 2012.

PubMed

Chen, Jing-Jing; Ma, Xiao-Jing; Liu, Fang; Yan, Wei-Li; Huang, Mei-Rong; Huang, Min; Huang, Guo-Ying

2016-01-01

This study was to investigate the epidemiologic trends of Kawasaki disease (KD) and coronary arterial lesions (CALs) in Shanghai from 2008 through 2012. Data were collected by using the network of the KD research group established during the first survey in Shanghai to conduct the third survey, covering the period from 2008 through 2012. Clinical records of 2304 patients with acute KD were retrospectively reviewed. Epidemiologic features of KD were investigated. Univariate and multivariate analyses were performed to identify the risk factors for CAL in patients with KD. The data were compared with the previous 2 surveys covering the periods from 1998 to 2002 and 2003 to 2007, respectively. The average incidence of KD was 30.3 to 71.9 per 100,000 children aged 0-4 years from 2008 through 2012. Age at onset ranged from 32 days to 11.7 years (median: 2.3 years). The occurrence of KD was more common in summer and spring. A total of 365 (15.9%) cases developed CAL defined as ectasia or aneurysm. Male, age ≤ 1 year, intravenous immunoglobulin (IVIG) unresponsiveness, a smaller administrative dosage and the delayed administration of IVIG (>10 days) were independent risk factors for CAL. The occurrence of CAL seemed less frequent in patients who received IVIG within 5 days after onset of illness. The incidence of KD in children has increased over time, and the development of CAL decreased in the past 5 years in Shanghai. Earlier treatment with IVIG (<5 days) was associated with reduced CAL among patients with KD.

The Clinical Profile of Kawasaki Disease in Algerian Children: A Single Institution Experience.

PubMed

Boudiaf, Houda; Achir, Moussa

2016-04-01

Kawasaki disease (KD) in an acute vasculitis of unknown etiology. The epidemiological data available for Algerian patients remains insufficient. To describe the demographic, clinical features of children with KD and to identify the risk factors for developing coronary artery lesions (CAL). This retrospective study included children admitted with KD at the pediatric hospital in Algiers from January 2005 to December 2014. One hundred thirty-three patients (82 boys and 51 girls) with a mean age of 31 months were identified. The most common sign was fever, rash, oral changes and conjunctivitis. The cardiac complications were CAL (22.5%), pericarditis (2%) and myocarditis (1.5%). The independent variable for prediction of CAL was duration of fever >10 days, male gender and platelet count >450,000/mm3 CONCLUSION: The incidence of cardiovascular complications is high. Knowledge of KD among Algerian pediatricians should be enhanced to guarantee appropriate treatment of this disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Kawasaki disease with G6PD deficiency--report of one case and literature review.

PubMed

Chen, Chia-Hao; Lin, Li-Yan; Yang, Kuender D; Hsieh, Kai-Sheng; Kuo, Ho-Chang

2014-06-01

Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are younger than 5 years. The most serious complications are coronary artery aneurysms and sequelae of vasculitis with the subsequent development of coronary artery aneurysm. According to the literature, intravenous immunoglobulin (IVIG) plus high-dose aspirin (acetylsalicylic acid) were standard treatment for KD, whereas low-dose aspirin (3-5 mg/kg/day) was used for thrombocytosis in KD via antiplatelet effect. However, aspirin has been reported to have hemolytic potential in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report a child with G6PD-deficiency who has KD, and review the literature. Copyright © 2012. Published by Elsevier B.V.

[Kawasaki disease is more prevalent in rural areas of Catalonia (Spain)].

PubMed

Sánchez-Manubens, Judith; Antón, Jordi; Bou, Rosa; Iglesias, Estibaliz; Calzada-Hernandez, Joan; Rodó, Xavier; Morguí, Josep-Antón

2017-10-01

Kawasaki disease (KD) is an acute self-limited systemic vasculitis relatively common in childhood. The etiology of KD is still unknown, although clinical, laboratory and epidemiological features suggest an infectious origin or trigger. Differences on incidence between countries have been related to specific genetic factors, ethnicity, country of birth and some other sociocultural and environmental factors. We present a population-based study on incidence of KD in Catalonia (Spain), focusing on differences between patients in rural and non-rural areas of the region. Observational population-based study including all Pediatric Units in Catalan hospitals, between 2004 and 2014. A 12-month (March 2013-March 2014) prospective collection of new cases of KD was carried out to determine the incidence of KD. The rest of the data was retrieved retrospectively. Data from 399 patients over the 10-year study period was analyzed. Among the total KD patients, 353 (88.5%) lived in non-rural areas and 46 (11.5%) in rural areas. It was found that there is a significant difference (P<.001) between the percentage of rural population observed in patients with KD (11.5%), and the expected 5% of the Catalan population. This is the first population-based study showing significant differences on KD incidence rates between rural and non-rural areas. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Incidence, epidemiology and clinical features of Kawasaki disease in Catalonia, Spain.

PubMed

Sánchez-Manubens, Judith; Antón, Jordi; Bou, Rosa; Iglesias, Estíbaliz; Calzada-Hernandez, Joan

2016-01-01

To assess the incidence, epidemiology and clinical features of Kawasaki disease (KD) in Catalonia (northeast region of Spain). This was an observational population-based study including all Paediatric Units in Catalonia, under both public and private management. Retrospective data retrieval was performed for 10 years (2004-2013). A 12-month (March 2013 to March 2014) prospective collection of new cases of KD was carried out to determine the incidence of KD. Data from 399 patients over the 10-year study period was analysed, revealing that 233 (58.4%) had complete KD, 159 (39.8) incomplete KD and 7 (1.7%) were considered atypical KD. Mean annual incidence was 3.5/105 children <14 years old (yo) and 8/105 children <5 yo (mean age 37±33 months, range 1.3-191.3). KD was more frequent in boys (59.6%, p<0.001) and in rural areas (p<0.001). Patients with IVIG non-responsiveness, need of a 2(nd) IVIG dose, delay of treatment >10(th) day of illness, ages <1 yo and >8 yo and the presence of sterile piuria, aseptic meningitis, abdominal pain and uveitis at diagnosis were found to have higher risk of coronary aneurisms (CAA) (p<0.05). This is the first population-based study on the epidemiology of KD in the western Mediterranean area. Incidence, clinical features and treatment plans in our cohort are similar to those described in other European studies.

The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer

PubMed Central

1993-01-01

Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by progressive rigidity of the body musculature with superimposed painful spasms. An autoimmune origin of the disease has been proposed. In a caseload of more than 100 SMS patients, 60% were found positive for autoantibodies directed against the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Few patients, all women affected by breast cancer, were negative for GAD autoantibodies but positive for autoantibodies directed against a 128- kD synaptic protein. We report here that this antigen is amphiphysin. GAD and amphiphysin are nonintrinsic membrane proteins that are concentrated in nerve terminals, where a pool of both proteins is associated with the cytoplasmic surface of synaptic vesicles. GAD and amphiphysin are the only two known targets of CNS autoimmunity with this distribution. This finding suggests a possible link between autoimmunity directed against cytoplasmic proteins associated with synaptic vesicles and SMS. PMID:8245793

A comprehensive study of small non-frameshift insertions/deletions in proteins and prediction of their phenotypic effects by a machine learning method (KD4i)

PubMed Central

2014-01-01

Background Small insertion and deletion polymorphisms (Indels) are the second most common mutations in the human genome, after Single Nucleotide Polymorphisms (SNPs). Recent studies have shown that they have significant influence on genetic variation by altering human traits and can cause multiple human diseases. In particular, many Indels that occur in protein coding regions are known to impact the structure or function of the protein. A major challenge is to predict the effects of these Indels and to distinguish between deleterious and neutral variants. When an Indel occurs within a coding region, it can be either frameshifting (FS) or non-frameshifting (NFS). FS-Indels either modify the complete C-terminal region of the protein or result in premature termination of translation. NFS-Indels insert/delete multiples of three nucleotides leading to the insertion/deletion of one or more amino acids. Results In order to study the relationships between NFS-Indels and Mendelian diseases, we characterized NFS-Indels according to numerous structural, functional and evolutionary parameters. We then used these parameters to identify specific characteristics of disease-causing and neutral NFS-Indels. Finally, we developed a new machine learning approach, KD4i, that can be used to predict the phenotypic effects of NFS-Indels. Conclusions We demonstrate in a large-scale evaluation that the accuracy of KD4i is comparable to existing state-of-the-art methods. However, a major advantage of our approach is that we also provide the reasons for the predictions, in the form of a set of rules. The rules are interpretable by non-expert humans and they thus represent new knowledge about the relationships between the genotype and phenotypes of NFS-Indels and the causative molecular perturbations that result in the disease. PMID:24742296

Building a Natural Language Processing Tool to Identify Patients With High Clinical Suspicion for Kawasaki Disease from Emergency Department Notes.

PubMed

Doan, Son; Maehara, Cleo K; Chaparro, Juan D; Lu, Sisi; Liu, Ruiling; Graham, Amanda; Berry, Erika; Hsu, Chun-Nan; Kanegaye, John T; Lloyd, David D; Ohno-Machado, Lucila; Burns, Jane C; Tremoulet, Adriana H

2016-05-01

Delayed diagnosis of Kawasaki disease (KD) may lead to serious cardiac complications. We sought to create and test the performance of a natural language processing (NLP) tool, the KD-NLP, in the identification of emergency department (ED) patients for whom the diagnosis of KD should be considered. We developed an NLP tool that recognizes the KD diagnostic criteria based on standard clinical terms and medical word usage using 22 pediatric ED notes augmented by Unified Medical Language System vocabulary. With high suspicion for KD defined as fever and three or more KD clinical signs, KD-NLP was applied to 253 ED notes from children ultimately diagnosed with either KD or another febrile illness. We evaluated KD-NLP performance against ED notes manually reviewed by clinicians and compared the results to a simple keyword search. KD-NLP identified high-suspicion patients with a sensitivity of 93.6% and specificity of 77.5% compared to notes manually reviewed by clinicians. The tool outperformed a simple keyword search (sensitivity = 41.0%; specificity = 76.3%). KD-NLP showed comparable performance to clinician manual chart review for identification of pediatric ED patients with a high suspicion for KD. This tool could be incorporated into the ED electronic health record system to alert providers to consider the diagnosis of KD. KD-NLP could serve as a model for decision support for other conditions in the ED. © 2016 by the Society for Academic Emergency Medicine.

Pregnancy in women with a history of Kawasaki disease: management and outcomes.

PubMed

Gordon, C T; Jimenez-Fernandez, S; Daniels, L B; Kahn, A M; Tarsa, M; Matsubara, T; Shimizu, C; Burns, J C; Gordon, J B

2014-10-01

To characterise the obstetrical management and outcomes in a series of women with a history of Kawasaki disease (KD) in childhood. Retrospective case series. Tertiary healthcare setting in the USA. Women with a history of KD in childhood. Women completed a detailed health questionnaire and participated in research imaging studies as part of the San Diego Adult KD Collaborative Study. Obstetrical management, complications during pregnancy and delivery, and infant outcomes. Ten women with a history of KD in childhood carried a total of 21 pregnancies to term. There were no cardiovascular complications during labour and delivery despite important cardiovascular abnormalities in four of the ten subjects. Pregnancy was complicated by pre-eclampsia and the post-partum course was complicated by haemorrhage in one subject each. Two of the 21 progeny subsequently developed KD. Women with important cardiovascular sequelae from KD in childhood should be managed by a team that includes both a maternal-fetal medicine specialist and a cardiologist. Pre-pregnancy counselling should include delineation of the woman's current functional and structural cardiovascular status and appropriate adjustment of medications, but excellent outcomes are possible with appropriate care. Review of the English and Japanese literature on KD and pregnancy revealed the occurrence of myocardial infarction during pregnancy in women with missed KD and aneurysms that were not diagnosed until their acute event. Our study highlights the need for counselling with regard to the increased genetic risk of KD in offspring born to these mothers. © 2014 Royal College of Obstetricians and Gynaecologists.

Parental anxiety associated with Kawasaki disease in previously healthy children.

PubMed

Chahal, Nita; Clarizia, Nadia A; McCrindle, Brian W; Boydell, Katherine M; Obadia, Maya; Manlhiot, Cedric; Dillenburg, Rejane; Yeung, Rae S M

2010-01-01

The objective of this study was to explore the lived experience of parents of children diagnosed with Kawasaki disease (KD) and to identify factors associated with increased levels of parental anxiety. Three focus groups were conducted including 25 parents of 17 patients with KD, seven (41%) of whom had coronary artery complications. A conceptual model was developed to depict parental experiences and illustrate the key issues related to heightened anxiety. Themes identified included anxiety related to the child's sudden illness and delay in obtaining a correct diagnosis because of the lack of health care providers' awareness and knowledge regarding KD. Parents were frustrated by the lack of information available in lay language and the limited scientific knowledge regarding the long-term consequences of the disease. Parents also reported positive transformations and different perspective toward challenges in life. However, the parents of children with coronary artery complications expressed persistent anxiety even years after the acute phase of the illness due to the uncertainty of the long-term prognosis. There remains a critical need for richly textured research data on the perspective and experience of families of children with KD. Copyright 2010 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

Kawasaki Disease Presenting as Acute Intestinal Obstruction

PubMed Central

Lone, Yasir Ahmad; Menon, Jagadeesh; Menon, Prema; Vaiphei, Kim; Narasimha Rao, Katragadda Lakshmi; Thapa, Baburam; Gupta, Kirti

2017-01-01

Kawasaki disease (KD) is an acute febrile illness of childhood associated with vasculitis of medium-sized arteries especially the coronary arteries. Typical clinical features involving the skin, mucous surfaces, etc., occur sequentially over a few days. We report a rare presentation of KD as a surgical abdomen in a 2-year-old boy. Awareness of this presentation is important as it can otherwise lead to a delay in starting potentially life-saving intervention like intravenous immunoglobulins for cardiac complications kept cryptic by the manifest acute abdomen. PMID:28694577

Cardiopulmonary Function, Exercise Capacity, and Echocardiography Finding of Pediatric Patients With Kawasaki Disease: An Observational Study.

PubMed

Tuan, Sheng-Hui; Li, Min-Hui; Hsu, Miao-Ju; Tsai, Yun-Jeng; Chen, Yin-Han; Liao, Tin-Yun; Lin, Ko-Long

2016-01-01

Coronary artery (CA) abnormalities influence exercise capacity (EC) of patients with Kawasaki disease (KD), and Z-score of CA is a well established method for detecting CA aneurysm. We studied the influence of KD on cardiopulmonary function and EC; meanwhile we analyzed echocardiographic findings of KD patients. We also assessed the correlation between CA Z-score and EC of KD patients to see if CA Z-score of KD patients could reflect EC during exercise.Sixty-three KD patients were recruited as KD group 1 from children (aged 5-18 y) who received transthoracic echocardiographic examinations and symptom-limited treadmill exercise test for regular follow-up of KD from January 2010 to October 2014 in 1 medical center. We then divided KD group 1 into KD group 2 (<5 y, n = 12) and KD group 3 (≥5 y, n = 51) according to time interval between KD onset to when patients received test. Control groups were matched by age, sex, and body mass index. Max-Z of CA was defined as the maximal Z-score of the proximal LCA or RCA by Dalliarre equation or Fuse calculator.All routine parameters measured during standard exercise test were similar between KD and control groups, except that peak rate pressure products (PRPPs) in KD group 1 to 3 were all lower than corresponding control groups significantly (P = 0.010, 0.020, and 0.049, respectively). PRPPs correlated with Max-Z of CA by both equations modest inversely (by Dallaire, P = 0.017, Spearman rho = -0.301; by Fuse, P = 0.014, Spearman rho = -0.309).Our study recruited larger number of KD patients and provided a newer data of EC of KD patients. Our finding suggests that after acute stage of KD, patients could maintain normal cardiorespiratory fitness. Therefore, we believe that it is important to promote cardiovascular health to KD patients and KD patients should exercise as normal peers. However, since KD patients might still have compromised coronary perfusion during exercise, it remains crucial to

Detection of the human 70-kD and 60-kD heat shock proteins in the vagina: relation to microbial flora, vaginal pH, and method of contraception.

PubMed Central

Giraldo, P; Neuer, A; Ribeiro-Filho, A; Linhares, I; Witkin, S S

1999-01-01

The expression of the 60-kD and 70-kD heat shock proteins (hsp60 and hsp70) in the vaginas of 43 asymptomatic women of reproductive age with or without a history of recurrent vulvovaginitis (RVV) were compared. Vaginal wash samples were obtained and assayed by enzyme-linked immunosorbent assay (ELISA) for human hsp60 and hsp70. Heat shock protein 70 was not detected in any of the 19 women with no history of RVV, and hsp60 was present in only one woman in this group. In contrast, in the RVV group, 11 (45.8%) were hsp60-positive and eight (33.3%) were hsp70-positive. The presence of either heat shock protein in the vagina was associated with an elevated vaginal pH (>4.5). Bacterial vaginosis or Candida was identified in some of the asymptomatic subjects; their occurrence was significantly higher in women with vaginal hsp70 than in women with no heat shock proteins. Oral contraceptives were used by 35.7% of subjects who were negative for vaginal heat shock proteins, as opposed to only 12.5% of women who were positive for hsp70 and 8.3% who were positive for hsp60. Expression of heat shock proteins in the vagina may indicate an altered vaginal environment and a susceptibility to vulvovaginal symptoms. PMID:10231004

Validation of the Andon KD5031 for clinical use and self-measurement according to the European Society of Hypertension International Protocol.

PubMed

Wu, Ning; Zhang, Xuezhong; Wang, Wen; Zhang, Hongye

2016-10-01

This study aimed to evaluate the accuracy of the automated oscillometric upper arm blood pressure (BP) monitor Andon KD5031 for home BP monitoring according to the European Society of Hypertension International Protocol revision 2010. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were sequentially measured in 33 participants using the standard mercury sphygmomanometer and the Andon KD5031 device. Ninety-nine pairs of comparisons were obtained from 33 participants for analysis. The KD5031 device achieved the targets in part 1 of the validation study. The number of absolute differences between the device and the observers within a range of 5, 10, and 15 mmHg was 66/99, 93/99, and 98/99, respectively, for SBP and 72/99, 94/99, and 99/99, respectively, for DBP. The device also achieved the targets in part 2 of the validation study. Twenty-six participants for both SBP and DBP had at least two of the three device-observer differences within 5 mmHg (required ≥24). The number of participants without a device-observer difference within 5 mmHg was one for SBP and three for DBP (required ≤3). The Andon upper arm BP monitor KD5031 has passed the International Protocol requirements, and it can be recommended for clinical use and self-measurement in adults.

Validation of the Andon KD595 for clinical use and self-measurement according to the European Society of Hypertension International Protocol.

PubMed

Wu, Ning; Zhang, Xuezhong; Wang, Wen; Zhang, Hongye

2016-04-01

This study aimed to evaluate the accuracy of the automated oscillometric upper arm blood pressure monitor Andon KD595 for home blood pressure monitoring according to the European Society of Hypertension International Protocol revision 2010. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were sequentially measured in 33 participants using the standard mercury sphygmomanometer and the Andon KD595 device. Ninety-nine pairs of comparisons were obtained from 33 participants for analysis. The KD595 device achieved the targets in part 1 of the validation study. The number of absolute differences between the device and the observers within a range of 5, 10, and 15 mmHg was 72/99, 93/99, and 96/99, respectively, for SBP and 72/99, 96/99, and 99/99, respectively, for DBP. The device also achieved the targets in part 2 of the validation study. A total of 28 and 25 participants had at least two of the three device-observer differences within 5 mmHg (required≥24) for SBP and DBP, respectively. The number of participants without device-observer difference within 5 mmHg was two for SBP and two for DBP (required≤3). The Andon upper arm blood pressure monitor KD595 has passed the International Protocol requirements and it can be recommended for clinical use and self-measurement in adults.

Pro-inflammatory cytokine single nucleotide polymorphisms in Kawasaki disease.

PubMed

Assari, Raheleh; Aghighi, Yahya; Ziaee, Vahid; Sadr, Maryam; Rahmani, Farzaneh; Rezaei, Arezou; Sadr, Zeinab; Moradinejad, Mohammad Hassan; Raeeskarami, Seyed Reza; Rezaei, Nima

2016-07-25

Kawasaki disease (KD) is a systemic vasculitis of children associated with cardiovascular sequelae. Proinflammatory cytokines play a major role in KD pathogenesis. However, their role is both influenced and modified by regulatory T-cells. IL-1 gene cluster, IL-6 and TNF-α polymorphisms have shown significant associations with some vasculitides. Herein we investigated their role in KD. Fifty-five patients with KD who were randomly selected from referrals to the main pediatric hospital were enrolled in this case-control study. Single nucleotide polymorphisms (SNPs) of the following genes were assessed in patients and 140 healthy subjects as control group: IL-1α at -889 (rs1800587), IL-1β at -511 (rs16944), IL-1β at +3962 (rs1143634), IL-1R at Pst-I 1970 (rs2234650), IL-1RN/A at Mspa-I 11100 (rs315952), TNF-α at -308 (rs1800629), TNF-α at -238, IL-6 at -174 (rs1800795) and IL-6 at +565. Twenty-one percent of the control group had A allele at TNF-α -238 while only 8% of KD patients had A allele at this position (P = 0.003, OR [95%CI] = 0.32 [0.14-0.71]). Consistently, TNF-α genotype GG at -238 had significant association with KD (OR [95% CI] = 4.31 [1.79-10.73]). Most controls carried the CG genotype at IL-6 -174 (n = 93 [66.9%]) while GG genotype was the most common genotype (n = 27 [49%]) among patients. Carriers of the GG haplotype at TNF-α (-308, -238) were significantly more prevalent among the KD group. No association was found between IL-1 gene cluster, allelic or haplotypic variants and KD. TNF-α GG genotype at -238 and GG haplotype at positions -308 and -238 were associated with KD in an Iranian population. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

On the nonlinear stability of mKdV breathers

NASA Astrophysics Data System (ADS)

Alejo, Miguel A.; Muñoz, Claudio

2012-11-01

Breather modes of the mKdV equation on the real line are known to be elastic under collisions with other breathers and solitons. This fact indicates very strong stability properties of breathers. In this communication we describe a rigorous, mathematical proof of the stability of breathers under a class of small perturbations. Our proof involves the existence of a nonlinear equation satisfied by all breather profiles, and a new Lyapunov functional which controls the dynamics of small perturbations and instability modes. In order to construct such a functional, we work in a subspace of the energy one. However, our proof introduces new ideas in order to attack the corresponding stability problem in the energy space. Some remarks about the sine-Gordon case are also considered.

High-density Genotyping of Immune Loci in Kawasaki Disease and IVIG Treatment Response in European-American Case-parent Trio Study

PubMed Central

Shendre, Aditi; Wiener, Howard W.; Zhi, Degui; Vazquez, Ana I; Portman, Michael A.; Shrestha, Sadeep

2014-01-01

Kawasaki disease (KD) is a diffuse and acute small-vessel vasculitis observed in children and has genetic and autoimmune components. We genotyped 112 case-parent trios of European decent (confirmed by AIMS) using the ImmunoChip array and performed association analyses with susceptibility to KD and IVIG non-response. KD susceptibility was assessed using the transmission disequilibrium test whereas IVIG non-response was evaluated using multivariable logistic regression analysis. We replicated SNPs in three gene regions (FCGR, CD40/CDH22, and HLA-DQB2/HLA-DOB) that have been previously associated with KD and provide support to other findings of several novel SNPs in genes with potential pathway in KD pathogenesis. SNP rs838143 in the 3′ UTR of FUT1 gene (2.7×10-5) and rs9847915 in the intergenic region of LOC730109 ∣ BRD7P2 (6.81×10-7) were the top hits for KD susceptibility in additive and dominant models, respectively. The top hits for IVIG responsiveness were rs1200332 in the intergenic region of BAZ1A ∣ C14orf19 (1.4×10-4) and rs4889606 in the intron of the STX1B gene (6.95×10-5) in additive and dominant models, respectively. Our study suggests that genes and biological pathways involved in autoimmune diseases play an important role in the pathogenesis of KD and IVIG response mechanism. PMID:25101798

Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody.

PubMed

Fox, D A; Hussey, R E; Fitzgerald, K A; Acuto, O; Poole, C; Palley, L; Daley, J F; Schlossman, S F; Reinherz, E L

1984-09-01

By using a murine monoclonal antibody produced against an IL 2-dependent human T cell line, we defined a T lineage-specific molecule, termed Ta1, that is expressed strongly on activated T lymphocytes of both the T4 and T8 subsets, as well as on T cell lines and clones, but only weakly on a fraction of resting T cells. SDS-PAGE analysis of immunoprecipitates from 125I-labeled, activated T cells demonstrates a single major band of apparent m.w. 105 KD under both reducing and nonreducing conditions. Unlike anti-IL 2 receptor antibodies, anti-Ta1 does not inhibit T cell proliferative responses to mitogen, antigen, or IL 2-containing medium. Moreover, anti-Ta1 has no effect on T cell-mediated cytotoxicity. Ta1 appears to be a novel human T cell-specific activation antigen that may serve as a useful marker of T cell activation in human disease.

Marked Acceleration of Atherosclerosis following Lactobacillus casei induced Coronary Arteritis in a Mouse Model of Kawasaki Disease

PubMed Central

Chen, Shuang; Lee, Young Ho; Crother, Timothy R.; Fishbein, Michael; Zhang, Wenxuan; Yilmaz, Atilla; Shimada, Kenichi; Schulte, Danica J; Lehman, Thomas J.A.; Shah, Prediman K.; Arditi, Moshe

2012-01-01

Objective To investigate if Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki Disease (KD) accelerates atherosclerosis in hypercholesterolemic mice. Method and Resuslts Apoe−/− or Ldlr−/− mice were injected with LCWE (KD mice) or PBS, fed high fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses (AS), arch (AC) and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared to lesions in control mice despite similar cholesterol levels. Both Apoe−/− KD and Ldlr−/− KD mice showed dramatic acceleration in atherosclerosis vs. controls, with increases in en face aortic atherosclerosis and plaque size in both the AS and AC plaques. Accelerated atherosclerosis was associated with increased circulating IL-12p40, IFN-γ, TNF-α, and increased macrophage, DC, and T cell recruitment in lesions. Furthermore, daily injections of the IL-1Ra, which inhibits LCWE induced KD vasculitis, prevented the acceleration of atherosclerosis. Conclusions Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults. PMID:22628430

Resistance to intravenous immunoglobulin in children with Kawasaki disease

PubMed Central

Tremoulet, Adriana H.; Best, Brookie M.; Song, Sungchan; Wang, Susan; Corinaldesi, Elena; Eichenfield, Julia R.; Martin, Danielle D.; Newburger, Jane W.; Burns, Jane C.

2008-01-01

Objectives To explore the increased incidence of intravenous immunoglobulin (IVIG) resistance among San Diego County Kawasaki disease (KD) patients in 2006 and to evaluate a scoring system to predict IVIG-resistant patients with KD. Study design We performed a retrospective review of patients with KD treated within 10 days of fever onset. Using multivariate analysis, independent predictors of IVIG-resistance were combined into a scoring system. Results In 2006, 38.3 % of patients with KD in San Diego County were IVIG-resistant, a significant increase over previous years. IVIG-resistance was not associated with a particular brand or lot of IVIG. Resistant patients were diagnosed earlier, had higher % bands, and higher concentrations of C-reactive protein, alanine aminotransferase, and γ-glutamyl transferase (GGT). They also had lower platelet counts and age-adjusted hemoglobin (zHgb) concentrations and were more likely to have aneurysms (p=0.0008). A scoring system developed to predict IVIG-resistant patients using illness day, % bands, GGT, and zHgb, had a sensitivity of 73.3% and specificity of 61.9%. Conclusions An unexplained increase in IVIG-resistance was noted among patients with KD in San Diego County in 2006. Scoring systems based on demographic and laboratory data were insufficiently accurate to be clinically useful in our ethnically diverse population. PMID:18571548

Development of a large field-of-view KD potassium di-deuterium phosphate modulator: Center Director's Discretionary Fund

NASA Technical Reports Server (NTRS)

West, E. A.

1993-01-01

Magnetographs, which measure polarized light, allow solar astronomers to infer the magnetic field intensity on the Sun. The Marshall Space Flight Center (MSFC) Vector Magnetograph is such an imaging instrument. The instrument requires rapid modulation between polarization states to minimize seeing effects. The accuracy of those polarization measurements is dependent on stable modulators with small field-of-view errors. Although these devices are very important in ground-based telescopes, extending the field of view of electro-optical crystals such as KD*Ps (potassium di-deuterium phosphate) could encourage the development of these devices for other imaging applications. The work that was done at MSFC as part of the Center Director's Discretionary Fund (CDDF) to reduce the field-of-view errors of instruments that use KD*P modulators in their polarimeters is described.

A 5-year-old boy with only fever and giant coronary aneurysms: the enigma of Kawasaki disease?

PubMed

Vignesh, Pandiarajan; Bhattad, Sagar; Singhal, Manphool; Singh, Surjit

2016-08-01

Epidemiological case definition of Kawasaki disease (KD) by the American Heart Association requires the presence of fever and four of the following: eye signs, oral mucosal changes, skin rashes, limb edema, and unilateral cervical lymphadenopathy. Incomplete KD is a well-known entity where there is lack of some of mucocutaneous features, and this occurs more often in infants. We report a 5-year-old boy with KD and giant coronary aneurysms, who presented only with fever and there is complete lack of skin and mucosal manifestations at presentation.

The Barley Magnesium Chelatase 150-kD Subunit Is Not an Abscisic Acid Receptor1[OA

PubMed Central

Müller, André H.; Hansson, Mats

2009-01-01

Magnesium chelatase is the first unique enzyme of the chlorophyll biosynthetic pathway. It is composed of three gene products of which the largest is 150 kD. This protein was recently identified as an abscisic acid receptor in Arabidopsis (Arabidopsis thaliana). We have evaluated whether the barley (Hordeum vulgare) magnesium chelatase large subunit, XanF, could be a receptor for the phytohormone. The study involved analysis of recombinant magnesium chelatase protein as well as several induced chlorophyll-deficient magnesium chelatase mutants with defects identified at the gene and protein levels. Abscisic acid had no effect on magnesium chelatase activity and binding to the barley 150-kD protein could not be shown. Magnesium chelatase mutants showed a wild-type response in respect to postgermination growth and stomatal aperture. Our results question the function of the large magnesium chelatase subunit as an abscisic acid receptor. PMID:19176716

Influence of Latitude on the Prevalence of Kawasaki Disease: A Retrospective Cohort Study from the Taiwan National Health Insurance Database and Review of the Literature.

PubMed

Chang, Chaw-Liang; Wong, Chih-Shung; Yang, Yi-Chen; Chiu, Nan-Chang

2018-04-25

Background: Countries at higher latitudes have higher incidence rates of Kawasaki disease (KD) than do countries at lower latitudes in the Asian and West Pacific area. However, the precise influence of latitude on KD incidence rates requires further clarification. Methods: We searched the Longitudinal Health Insurance Database 2005 to retrieve patients’ medical records from 1996 to 2009. The patients with KD were categorized as living in northern, middle, and southern Taiwan; the period prevalence of KD for each area was determined. Climate variables, including temperature, sunshine duration, precipitation, and relative humidity, were collected from the Taiwan Central Weather Bureau. The effect of latitude on the period KD prevalence and the correlation between climate variables and KD prevalence were calculated. Results: After patients without complete data excluded, a total of 61,830 children up to 10 years old were retrieved, from which 404 patients with KD were recognized. The period prevalence of KD increased significantly with latitude ( p = 0.0004). Climate variables associated with high temperature demonstrated a connection with KD prevalence; however, this correlation was not statistically significant. Conclusions: Our study demonstrated that higher latitude is associated with a higher KD prevalence in Taiwan.

UNDERSTANDING VARIATION IN PARTITION COEFFICIENT KD, VALUES, VOLUME III: AMERICIUM, ARSENIC, CURIUM, IODINE, NEPTUNIUM, RADIUM, AND TECHNETIUM

EPA Science Inventory

This report describes the conceptualization, measurement, and use of the partition (or distribution) coefficient, Kd, parameter, and the geochemical aqueous solution and sorbent properties that are most important in controlling adsorption/retardation behavior of selected contamin...

Augmented TLR2 expression on monocytes in both human Kawasaki disease and a mouse model of coronary arteritis.

PubMed

Lin, I-Chun; Kuo, Ho-Chang; Lin, Ying-Jui; Wang, Feng-Shen; Wang, Lin; Huang, Shun-Chen; Chien, Shao-Ju; Huang, Chien-Fu; Wang, Chih-Lu; Yu, Hong-Ren; Chen, Rong-Fu; Yang, Kuender D

2012-01-01

Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14

Augmented TLR2 Expression on Monocytes in both Human Kawasaki Disease and a Mouse Model of Coronary Arteritis

PubMed Central

Lin, I-Chun; Kuo, Ho-Chang; Lin, Ying-Jui; Wang, Feng-Shen; Wang, Lin; Huang, Shun-Chen; Chien, Shao-Ju; Huang, Chien-Fu; Wang, Chih-Lu; Yu, Hong-Ren; Chen, Rong-Fu; Yang, Kuender D.

2012-01-01

Background Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. Methods Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. Results Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. Conclusion This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2

Identification of Novel Susceptibility Loci for Kawasaki Disease in a Han Chinese Population by a Genome-Wide Association Study

PubMed Central

Huang, Li-Min; Huang, Fu-Yuan; Chiu, Nan-Chang; Chen, Ming-Ren; Chi, Hsin; Lee, Yann-Jinn; Chang, Li-Ching; Liu, Yi-Min; Wang, Hsiang-Hua; Chen, Chien-Hsiun; Chen, Yuan-Tsong; Wu, Jer-Yuarn

2011-01-01

Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. Its etiology is unknown; however, epidemiological findings suggest that genetic predisposition underlies disease susceptibility. Taiwan has the third-highest incidence of KD in the world, after Japan and Korea. To investigate novel mechanisms that might predispose individuals to KD, we conducted a genome-wide association study (GWAS) in 250 KD patients and 446 controls in a Han Chinese population residing in Taiwan, and further validated our findings in an independent Han Chinese cohort of 208 cases and 366 controls. The most strongly associated single-nucleotide polymorphisms (SNPs) detected in the joint analysis corresponded to three novel loci. Among these KD-associated SNPs three were close to the COPB2 (coatomer protein complex beta-2 subunit) gene: rs1873668 (p = 9.52×10−5), rs4243399 (p = 9.93×10−5), and rs16849083 (p = 9.93×10−5). We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1) gene (rs149481, pbest = 4.61×10−5). Six SNPs (rs17113284, rs8005468, rs10129255, rs2007467, rs10150241, and rs12590667) clustered in an area containing immunoglobulin heavy chain variable regions genes, with pbest-values between 2.08×10−5 and 8.93×10−6, were also identified. This is the first KD GWAS performed in a Han Chinese population. The novel KD candidates we identified have been implicated in T cell receptor signaling, regulation of proinflammatory cytokines, as well as antibody-mediated immune responses. These findings may lead to a better understanding of the underlying molecular pathogenesis of KD. PMID:21326860

Innate immune responses following Kawasaki disease and toxic shock syndrome

PubMed Central

Messina, Nicole; Germano, Susie; Bonnici, Rhian; Freyne, Bridget; Cheung, Michael; Goldsmith, Greta; Kollmann, Tobias R.; Levin, Michael; Burgner, David; Curtis, Nigel

2018-01-01

The pathogenesis of Kawasaki disease (KD) remains unknown and there is accumulating evidence for the importance of the innate immune system in initiating and mediating the host inflammatory response. We compared innate immune responses in KD and toxic shock syndrome (TSS) participants more than two years after their acute illness with control participants to investigate differences in their immune phenotype. Toxic shock syndrome shares many clinical features with KD; by including both disease groups we endeavoured to explore changes in innate immune responses following acute inflammatory illnesses more broadly. We measured the in vitro production of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10 following whole blood stimulation with toll-like receptor and inflammasome ligands in 52 KD, 20 TSS, and 53 control participants in a case-control study. Analyses were adjusted for age, sex, and unstimulated cytokine concentrations. Compared to controls, KD participants have reduced IL-1ra production in response to stimulation with double stranded RNA (geometric mean ratio (GMR) 0.37, 95% CI 0.15, 0.89, p = 0.03) and increased IL-6 production in response to incubation with Lyovec™ (GMR 5.48, 95% CI 1.77, 16.98, p = 0.004). Compared to controls, TSS participants have increased IFN-γ production in response to peptidoglycan (GMR 4.07, 95% CI 1.82, 9.11, p = 0.001), increased IL-1β production to lipopolysaccharide (GMR 1.64, 95% CI 1.13, 2.38, p = 0.01) and peptidoglycan (GMR 1.61, 95% CI 1.11, 2.33, p = 0.01), and increased IL-6 production to peptidoglycan (GMR 1.45, 95% CI 1.10, 1.92, p = 0.01). Years following the acute illness, individuals with previous KD or TSS exhibit a pro-inflammatory innate immune phenotype suggesting a possible underlying immunological susceptibility or innate immune memory. PMID:29447181

Innate immune responses following Kawasaki disease and toxic shock syndrome.

PubMed

Chen, Katherine Y H; Messina, Nicole; Germano, Susie; Bonnici, Rhian; Freyne, Bridget; Cheung, Michael; Goldsmith, Greta; Kollmann, Tobias R; Levin, Michael; Burgner, David; Curtis, Nigel

2018-01-01

The pathogenesis of Kawasaki disease (KD) remains unknown and there is accumulating evidence for the importance of the innate immune system in initiating and mediating the host inflammatory response. We compared innate immune responses in KD and toxic shock syndrome (TSS) participants more than two years after their acute illness with control participants to investigate differences in their immune phenotype. Toxic shock syndrome shares many clinical features with KD; by including both disease groups we endeavoured to explore changes in innate immune responses following acute inflammatory illnesses more broadly. We measured the in vitro production of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10 following whole blood stimulation with toll-like receptor and inflammasome ligands in 52 KD, 20 TSS, and 53 control participants in a case-control study. Analyses were adjusted for age, sex, and unstimulated cytokine concentrations. Compared to controls, KD participants have reduced IL-1ra production in response to stimulation with double stranded RNA (geometric mean ratio (GMR) 0.37, 95% CI 0.15, 0.89, p = 0.03) and increased IL-6 production in response to incubation with Lyovec™ (GMR 5.48, 95% CI 1.77, 16.98, p = 0.004). Compared to controls, TSS participants have increased IFN-γ production in response to peptidoglycan (GMR 4.07, 95% CI 1.82, 9.11, p = 0.001), increased IL-1β production to lipopolysaccharide (GMR 1.64, 95% CI 1.13, 2.38, p = 0.01) and peptidoglycan (GMR 1.61, 95% CI 1.11, 2.33, p = 0.01), and increased IL-6 production to peptidoglycan (GMR 1.45, 95% CI 1.10, 1.92, p = 0.01). Years following the acute illness, individuals with previous KD or TSS exhibit a pro-inflammatory innate immune phenotype suggesting a possible underlying immunological susceptibility or innate immune memory.

Evaluation of echogenicity of the heart in Kawasaki disease.

PubMed

Nagata, Hazumu; Yamamura, Kenichiro; Uike, Kiyoshi; Nakashima, Yasutaka; Hirata, Yuichiro; Morihana, Eiji; Mizuno, Yumi; Ishikawa, Shiro; Hara, Toshiro

2014-08-01

Pathologic studies of the heart in patients with Kawasaki disease (KD) revealed vasculitis, valvulitis, myocarditis, and pericarditis. However, there have been no studies on the quantitative determination of multi-site echogenicity of the heart in KD patients. It is also undetermined whether the degree of echogenicity of each site of the heart in patients with KD might be related to the response to intravenous immunoglobulin (IVIG) treatment. In 81 KD patients and 30 control subjects, we prospectively analyzed echogenicity of the heart. Echogenicity was measured in four sites: coronary artery wall (CAW), mitral valve (MV), papillary muscle (PM), and ascending aortic wall (AAo wall) by the calibrated integrated backscatters (cIBs). The cIB values of all measurement sites at acute phase in KD patients were significantly higher than those in control subjects (KD patients vs control subjects; CAW, 19.8 ± 6.2 dB vs 14.5 ± 2.0 dB, p < 0.05; MV, 23.3 ± 5.3 dB vs 16.0 ± 3.3 dB, p < 0.05; PM, 22.4 ± 5.1 dB vs 12.7 ± 1.9 dB, p < 0.05; AAo wall, 25.3 ± 5.6 dB vs 18.3 ± 3.4 dB, p < 0.05). The cIB values of CAW at the acute phase in IVIG nonresponders were significantly higher than those in responders. Conclusion: Echogenicity of the heart in KD patients at the acute phase increased not only in the coronary artery wall but also in other parts of the heart. Echogenicity of CAW might be helpful in determining the unresponsiveness of IVIG treatment.

Opaque-2 is a transcriptional activator that recognizes a specific target site in 22-kD zein genes.

PubMed Central

Schmidt, R J; Ketudat, M; Aukerman, M J; Hoschek, G

1992-01-01

opaque-2 (o2) is a regulatory locus in maize that plays an essential role in controlling the expression of genes encoding the 22-kD zein proteins. Through DNase I footprinting and DNA binding analyses, we have identified the binding site for the O2 protein (O2) in the promoter of 22-kD zein genes. The sequence in the 22-kD zein gene promoter that is recognized by O2 is similar to the target site recognized by other "basic/leucine zipper" (bZIP) proteins in that it contains an ACGT core that is necessary for DNA binding. The site is located in the -300 region relative to the translation start and lies about 20 bp downstream of the highly conserved zein gene sequence motif known as the "prolamin box." Employing gel mobility shift assays, we used O2 antibodies and nuclear extracts from an o2 null mutant to demonstrate that the O2 protein in maize endosperm nuclei recognizes the target site in the zein gene promoter. Mobility shift assays using nuclear proteins from an o2 null mutant indicated that other endosperm proteins in addition to O2 can bind the O2 target site and that O2 may be associated with one of these proteins. We also demonstrated that in yeast cells the O2 protein can activate expression of a lacZ gene containing a multimer of the O2 target sequence as part of its promoter, thus confirming its role as a transcriptional activator. A computer-assisted search indicated that the O2 target site is not present in the promoters of zein genes other than those of the 22-kD class. These data suggest a likely explanation at the molecular level for the differential effect of o2 mutations on expression of certain members of the zein gene family. PMID:1392590

A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease.

PubMed

Kim, Jae-Jung; Hong, Young Mi; Sohn, Saejung; Jang, Gi Young; Ha, Kee-Soo; Yun, Sin Weon; Han, Myung Ki; Lee, Kyung-Yil; Song, Min Seob; Lee, Hyoung Doo; Kim, Dong Soo; Lee, Jong-Eun; Shin, Eun-Soon; Jang, Ji-Hyun; Lee, Yeon-Su; Kim, Sook-Young; Lee, Jong-Young; Han, Bok-Ghee; Wu, Jer-Yuarn; Kim, Kwi-Joo; Park, Young-Mi; Seo, Eul-Joo; Park, In-Sook; Lee, Jong-Keuk

2011-05-01

Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15-25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively (p < 1 × 10(-5)). Of these, one locus on chromosome 1p31 (rs527409) was replicated in 266 children with KD and 600 normal controls (odds ratio [OR] = 2.90, 95% confidence interval [CI] = 1.85-4.54, P (combined) = 1.46 × 10(-6)); and a PELI1 locus on chromosome 2p13.3 (rs7604693) was replicated in 86 KD patients with CALs and 600 controls (OR = 2.70, 95% CI = 1.77-4.12, P (combined) = 2.00 × 10(-6)). These results implicate a locus in the 1p31 region and the PELI1 gene locus in the 2p13.3 region as susceptibility loci for KD and CALs, respectively.

Kawasaki Disease-Specific Molecules in the Sera Are Linked to Microbe-Associated Molecular Patterns in the Biofilms

PubMed Central

Murata, Kenji; Kanno, Shunsuke; Nishio, Hisanori; Saito, Mitsumasa; Tanaka, Tamami; Yamamura, Kenichiro; Sakai, Yasunari; Takada, Hidetoshi; Miyamoto, Tomofumi; Mizuno, Yumi; Ouchi, Kazunobu; Waki, Kenji; Hara, Toshiro

2014-01-01

Background Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The innate immune system is involved in its pathophysiology at the acute phase. We have recently established a novel murine model of KD coronary arteritis by oral administration of a synthetic microbe-associated molecular pattern (MAMP). On the hypothesis that specific MAMPs exist in KD sera, we have searched them to identify KD-specific molecules and to assess the pathogenesis. Methods We performed liquid chromatography-mass spectrometry (LC-MS) analysis of fractionated serum samples from 117 patients with KD and 106 controls. Microbiological and LC-MS evaluation of biofilm samples were also performed. Results KD samples elicited proinflammatory cytokine responses from human coronary artery endothelial cells (HCAECs). By LC-MS analysis of KD serum samples collected at 3 different periods, we detected a variety of KD-specific molecules in the lipophilic fractions that showed distinct m/z and MS/MS fragmentation patterns in each cluster. Serum KD-specific molecules showed m/z and MS/MS fragmentation patterns almost identical to those of MAMPs obtained from the biofilms formed in vitro (common MAMPs from Bacillus cereus, Yersinia pseudotuberculosis and Staphylococcus aureus) at the 1st study period, and from the biofilms formed in vivo (common MAMPs from Bacillus cereus, Bacillus subtilis/Bacillus cereus/Yersinia pseudotuberculosis and Staphylococcus aureus) at the 2nd and 3rd periods. The biofilm extracts from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus aureus also induced proinflammatory cytokines by HCAECs. By the experiments with IgG affinity chromatography, some of these serum KD-specific molecules bound to IgG. Conclusions We herein conclude that serum KD-specific molecules were mostly derived from biofilms and possessed molecular structures common to MAMPs from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus

New insight into pesticide partition coefficient Kd for modelling pesticide fluvial transport: application to an agricultural catchment in south-western France.

PubMed

Boithias, Laurie; Sauvage, Sabine; Merlina, Georges; Jean, Séverine; Probst, Jean-Luc; Sánchez Pérez, José Miguel

2014-03-01

Pesticides applied on crops are leached with rainfall to groundwater and surface water. They threat the aquatic environment and may render water unfit for human consumption. Pesticide partitioning is one of the pesticide fate processes in the environment that should be properly formalised in pesticide fate models. Based on the analysis of 7 pesticide molecules (alachlor, atrazine, atrazine's transformation product deethylatrazine or DEA, isoproturon, tebuconazole and trifluralin) sampled from July 2009 to October 2010 at the outlet of the river Save (south-western France), the objectives of this study were (1) to check which of the environmental factors (discharge, pH, concentrations of total suspended matter (TSM), dissolved organic carbon (DOC) and particulate organic carbon (POC) could control the pesticide sorption dynamic, and (2) to establish a relationship between environmental factors, the partition coefficient Kd and the octanol/water distribution coefficient Kow. The comparison of physico-chemical parameters values during low flow and high flow shows that discharge, TSM and POC are the factors most likely controlling the pesticide sorption processes in the Save river network, especially for lower values of TSM (below 13mgL(-1)). We therefore express Kd depending on the widely literature-related variable Kow and on the commonly simulated variable TSM concentration. The equation can be implemented in any model describing the fluvial transport and fate of pesticides in both dissolved and sorbed phases, thus, Kd becomes a variable in time and space. The Kd calculation method can be applied to a wide range of catchments and organic contaminants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Enhanced biodegradation of mixed PAHs by mutated naphthalene 1,2-dioxygenase encoded by Pseudomonas putida strain KD6 isolated from petroleum refinery waste.

PubMed

Dutta, Kunal; Shityakov, Sergey; Das, Prangya P; Ghosh, Chandradipa

2017-12-01

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental pollutant that are given top priority to maintain water and soil quality to the most amenable standard. Biodegradation of PAHs by bacteria is the convenient option for decontamination on site or off site. The aim of the present study was to isolate and identify naturally occurring bacteria having mixed PAHs biodegradation ability. The newly isolated Pseudomonas putida strain KD6 was found to efficiently degrade 97.729% of 1500 mg L -1 mixed PAHs within 12 days in carbon-deficient minimal medium (CSM). The half-life ( t 1/2 ) and degradation rate constant ( k ) were estimated to be 3.2 and 0.2165 days, respectively. The first-order kinetic parameters in soil by strain KD6 had shown efficient biodegradation potency with the higher concentration of total PAHs (1500 mg kg -1 soil), t 1/2  = 10.44 days -1 . However, the biodegradation by un-inoculated control soil was found slower ( t 1/2  = 140 days -1 ) than the soil inoculated with P. putida strain KD6. The enzyme kinetic constants are also in agreement with chemical data obtained from the HPLC analysis. In addition, the sequence analysis and molecular docking studies showed that the strain KD6 encodes a mutant version of naphthalene 1,2-dioxygenase which have better Benzpyrene binding energy (-9.90 kcal mol -1 ) than wild type (-8.18 kcal mol -1 ) enzyme (chain A, 1NDO), respectively, with 0.00 and 0.08 RMSD values. The mutated naphthalene 1,2-dioxygenase nah Ac has six altered amino acid residues near to the ligand binding site. The strain KD6 could be a good bioresource for in situ or ex situ biodegradation of polycyclic aromatic hydrocarbon.

Clinical implications in laboratory parameter values in acute Kawasaki disease for early diagnosis and proper treatment.

PubMed

Seo, Yu-Mi; Kang, Hyun-Mi; Lee, Sung-Churl; Yu, Jae-Won; Kil, Hong-Ryang; Rhim, Jung-Woo; Han, Ji-Whan; Lee, Kyung-Yil

2018-05-01

This study aimed to analyse laboratory values according to fever duration, and evaluate the relationship across these values during the acute phase of Kawasaki disease (KD) to aid in the early diagnosis for early-presenting KD and incomplete KD patients. Clinical and laboratory data of patients with KD (n=615) were evaluated according to duration of fever at presentation, and were compared between patients with and without coronary artery lesions (CALs). For evaluation of the relationships across laboratory indices, patients with a fever duration of 5 days or 6 days were used (n=204). The mean fever duration was 6.6±2.3 days, and the proportions of patients with CALs was 19.3% (n=114). C-reactive proteins (CRPs) and neutrophil differential values were highest and hemoglobin, albumin, and lymphocyte differential values were lowest in the 6-day group. Patients with CALs had longer total fever duration, higher CRP and neutrophil differential values and lower hemoglobin and albumin values compared to patients without CALs. CRP, albumin, neutrophil differential, and hemoglobin values at the peak inflammation stage of KD showed positive or negative correlations each other. The severity of systemic inflammation in KD was reflected in the laboratory values including CRP, neutrophil differential, albumin, and hemoglobin. Observing changes in these laboratory parameters by repeated examinations prior to the peak of inflammation in acute KD may aid in diagnosis of early-presenting KD patients.

Pattern of subcutaneous fat during follow-up of a cohort of North Indian children with Kawasaki disease: a preliminary study.

PubMed

Suthar, Renu; Singh, Surjit; Bhalla, Anil Kumar; Attri, Savita Verma

2014-03-01

Kawasaki disease (KD) has been associated with abnormal lipid profiles. The latter, in turn, have been linked to changes in subcutaneous fat. In this comparative cross-sectional study we have quantified distribution of subcutaneous fat during follow-up of a cohort of North Indian children with KD. We compared 35 KD children (at least 2 years after disease) and 33 healthy controls. Study parameters included weight, height and skinfold thickness (SFT) over biceps, triceps, midaxillary, subscapular, medial calf and suprailiac areas. Waist and hip circumferences were also recorded. All parameters were measured four times at 6-monthly intervals using standardized techniques. Serum lipids were assayed in the study group. Study children were enrolled 3.7 ± 2.5 years after KD and mean age at enrolment was 8.26 ± 3.65 years. Suprailiac SFT measured higher in boys with KD (P ≤ 0.05). Biceps SFT was higher in the study group, but the difference was not significant. Other SFT were not affected. Waist and hip circumference was higher in the study group than controls (P ≤ 0.05). Waist/hip circumference ratio was not affected. Serum low-density lipoprotein cholesterol (LDL-C) and triglycerides were higher in the study group as compared to historical controls (95.60 ± 36.12 and 129.40 ± 64.62 mg/dL vs. 80.10 ± 2.20 and 91.1 ± 29.85; P ≤ 0.05). Total cholesterol and high-density lipoprotein cholesterol levels remained unaffected. Children with KD (especially boys) had increased subcutaneous fat deposition in the suprailiac region and waist, during follow-up. Serum LDL-C and triglycerides were elevated. KD children may have a tendency to develop central obesity. Further studies, with longer follow-up, would be necessary to show whether this has implications for development of coronary artery disease later in life. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Use of thermodynamic sorption models to derive radionuclide Kd values for performance assessment: Selected results and recommendations of the NEA sorption project

USGS Publications Warehouse

Ochs, M.; Davis, J.A.; Olin, M.; Payne, T.E.; Tweed, C.J.; Askarieh, M.M.; Altmann, S.

2006-01-01

For the safe final disposal and/or long-term storage of radioactive wastes, deep or near-surface underground repositories are being considered world-wide. A central safety feature is the prevention, or sufficient retardation, of radionuclide (RN) migration to the biosphere. To this end, radionuclide sorption is one of the most important processes. Decreasing the uncertainty in radionuclide sorption may contribute significantly to reducing the overall uncertainty of a performance assessment (PA). For PA, sorption is typically characterised by distribution coefficients (Kd values). The conditional nature of Kd requires different estimates of this parameter for each set of geochemical conditions of potential relevance in a RN's migration pathway. As it is not feasible to measure sorption for every set of conditions, the derivation of Kd for PA must rely on data derived from representative model systems. As a result, uncertainty in Kd is largely caused by the need to derive values for conditions not explicitly addressed in experiments. The recently concluded NEA Sorption Project [1] showed that thermodynamic sorption models (TSMs) are uniquely suited to derive K d as a function of conditions, because they allow a direct coupling of sorption with variable solution chemistry and mineralogy in a thermodynamic framework. The results of the project enable assessment of the suitability of various TSM approaches for PA-relevant applications as well as of the potential and limitations of TSMs to model RN sorption in complex systems. ?? by Oldenbourg Wissenschaftsverlag.

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan.

PubMed

Rodó, Xavier; Curcoll, Roger; Robinson, Marguerite; Ballester, Joan; Burns, Jane C; Cayan, Daniel R; Lipkin, W Ian; Williams, Brent L; Couto-Rodriguez, Mara; Nakamura, Yosikazu; Uehara, Ritei; Tanimoto, Hiroshi; Morguí, Josep-Anton

2014-06-03

Evidence indicates that the densely cultivated region of northeastern China acts as a source for the wind-borne agent of Kawasaki disease (KD). KD is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 y. We used residence times from simulations with the flexible particle dispersion model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. The postepidemic interval (1987-2010) and the extreme epidemics (1979, 1982, and 1986) pointed to the same source region. Results suggest a very short incubation period (<24 h) from exposure, thus making an infectious agent unlikely. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols compared with ground aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, consistent with the Candida animal model for KD, provide support for the concept and feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD, consistent with an agricultural source, a short incubation time and synchronized outbreaks. Our study suggests that the causative agent of KD is a preformed toxin or environmental agent rather than an organism requiring replication. We propose a new paradigm whereby an idiosyncratic immune response, influenced by host genetics triggered by an environmental exposure carried on winds, results in the clinical syndrome known as acute KD.

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan

PubMed Central

Rodó, Xavier; Curcoll, Roger; Robinson, Marguerite; Ballester, Joan; Burns, Jane C.; Cayan, Daniel R.; Lipkin, W. Ian; Williams, Brent L.; Couto-Rodriguez, Mara; Nakamura, Yosikazu; Uehara, Ritei; Tanimoto, Hiroshi; Morguí, Josep-Anton

2014-01-01

Evidence indicates that the densely cultivated region of northeastern China acts as a source for the wind-borne agent of Kawasaki disease (KD). KD is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 y. We used residence times from simulations with the flexible particle dispersion model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. The postepidemic interval (1987–2010) and the extreme epidemics (1979, 1982, and 1986) pointed to the same source region. Results suggest a very short incubation period (<24 h) from exposure, thus making an infectious agent unlikely. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols compared with ground aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, consistent with the Candida animal model for KD, provide support for the concept and feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD, consistent with an agricultural source, a short incubation time and synchronized outbreaks. Our study suggests that the causative agent of KD is a preformed toxin or environmental agent rather than an organism requiring replication. We propose a new paradigm whereby an idiosyncratic immune response, influenced by host genetics triggered by an environmental exposure carried on winds, results in the clinical syndrome known as acute KD. PMID:24843117

Distinctive interactions of the Arabidopsis homolog of the 30 kD subunit of the cleavage and polyadenylation specificity factor (AtCPSF30) with other polyadenylation factor subunits

USDA-ARS?s Scientific Manuscript database

Background: The Arabidopsis ortholog of the 30 kD subunit of the mammalian Cleavage and Polyadenylation Specificity Factor (AtCPSF30) is an RNA-binding endonuclease that is associated with other Arabidopsis CPSF subunits (orthologs of the 160, 100, and 73 kD subunits of CPSF). In order to better u...

Implications of method specific creatinine adjustments on General Medical Services chronic kidney disease classification

PubMed Central

Reynolds, Timothy M; Twomey, Patrick J

2007-01-01

Aims To evaluate the impact of different equations for calculation of estimated glomerular filtration rate (eGFR) on general practitioner (GP) workload. Methods Retrospective evaluation of routine workload data from a district general hospital chemical pathology laboratory serving a GP patient population of approximately 250 000. The most recent serum creatinine result from 80 583 patients was identified and used for the evaluation. eGFR was calculated using one of three different variants of the four‐parameter Modification of Diet in Renal Disease (MDRD) equation. Results The original MDRD equation (eGFR186) and the modified equation with assay‐specific data (eGFR175corrected) both identified similar numbers of patients with stage 4 and stage 5 chronic kidney disease (ChKD), but the modified equation without assay specific data (eGFR175) resulted in a significant increase in stage 4 ChKD. For stage 3 ChKD the eGFR175 identified 28.69% of the population, the eGFR186 identified 21.35% of the population and the eGFR175corrected identified 13.6% of the population. Conclusions Depending on the choice of equation there can be very large changes in the proportions of patients identified with the different stages of ChKD. Given that according to the General Medical Services Quality Framework, all patients with ChKD stages 3–5 should be included on a practice renal registry, and receive relevant drug therapy, this could have significant impacts on practice workload and drug budgets. It is essential that practices work with their local laboratories. PMID:17761741

Effective therapy with infliximab for clinically mild encephalitis/encephalopathy with a reversible splenial lesion in an infant with Kawasaki disease.

PubMed

Kurokawa, Yoshie; Masuda, Hiroshi; Kobayashi, Tohru; Ono, Hiroshi; Kato, Hitoshi; Imadome, Ken-Ichi; Abe, Jun; Abe, Yuichi; Ito, Shuichi; Ishiguro, Akira

2017-01-01

Kawasaki disease (KD) is a systemic vasculitis in infants. In KD, encephalopathy is rarely (0.1%) associated, however, clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has previously been reported in some pediatric patients. Here, we report on a 2-year-old girl who had KD complicated with MERS. The patient experienced generalized clonic convulsion and prolonged consciousness disturbance with fever for 2 days. Her head MRI showed a high signal intensity lesion in the splenium of the corpus callosum in diffusion-weighted images, and low apparent diffusion coefficient (ADC) values on day 3. An electroencephalogram showed high voltage slow waves on the occipital and parietal head. On the same day, it was confirmed that the patient showed all the main symptoms of KD. Based on these findings, we diagnosed her with MERS-complicated KD. Even though she was treated with immunoglobulin (total 4 g/kg) and pulsed-dose methylprednisolone, her fever and consciousness disturbance continued, and blood tests showed that inflammation markers remained high. We then treated the patient with infliximab on day 9, and within a few hours of the treatment her fever dropped and all symptoms of KD and consciousness disturbance disappeared. No recurrence of KD or other complications of KD occurred, and she was discharged on day 23. We propose that infliximab is an effective optional treatment for immunoglobulin/glucocorticoid-resistant KD with MERS. To clarify this possibility, further case accumulation is warranted.

Diagnostic accuracy of the clinical and CT findings for differentiating Kikuchi's disease and tuberculous lymphadenitis presenting with cervical lymphadenopathy.

PubMed

Baek, Hye Jin; Lee, Jeong Hyun; Lim, Hyun Kyung; Lee, Ha Young; Baek, Jung Hwan

2014-11-01

To determine the optimal clinical and CT findings for differentiating Kikuchi's disease (KD) and tuberculous lymphadenitis (TB) in patients presenting with cervical lymphadenopathy. From 2006 to 2010, 87 consecutive patients who were finally diagnosed with KD or TB were enrolled. Two radiologists performed independent analysis of contrast-enhanced neck CT images with regard to the involvement pattern, nodal or perinodal changes, and evidence of the previous infection. Significant clinical and CT findings of KD were determined by statistical analyses. Of the 87 patients, 27 (31%) were classified as having KD and 60 (69%) as having TB. Statistically significant findings of KD patients were younger age, presence of fever, involvement of ≥5 nodal levels or the bilateral neck, no or minimal nodal necrosis, marked perinodal infiltration, and no evidence of upper lung lesion or mediastinal lymphadenopathy. The presence of four or more statistically significant clinical and CT findings of KD had the largest area under the receiver-operating characteristic curve (A z = 0.861; 95% confidence intervals 0.801, 0.909), with a sensitivity of 89% and specificity of 83%. CT can be a helpful tool for differentiating KD from TB, especially when it is combined with the clinical findings.

Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients

PubMed Central

Huang, Ying-Hsien; Kuo, Ho-Chang; Huang, Fu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Yang, Ya-Ling; Sheen, Jiunn-Ming; Li, Sung-Chou; Kuo, Hsing-Chun

2016-01-01

Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD’s acute inflammatory phase. PMID:27187366

A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease.

PubMed

Kim, Jae-Jung; Yun, Sin Weon; Yu, Jeong Jin; Yoon, Kyung Lim; Lee, Kyung-Yil; Kil, Hong-Ryang; Kim, Gi Beom; Han, Myung-Ki; Song, Min Seob; Lee, Hyoung Doo; Ha, Kee Soo; Sohn, Sejung; Johnson, Todd A; Takahashi, Atsushi; Kubo, Michiaki; Tsunoda, Tatsuhiko; Ito, Kaoru; Onouchi, Yoshihiro; Hong, Young Mi; Jang, Gi Young; Lee, Jong-Keuk

2017-12-01

Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1.0 × 10 -5 ), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10 -11 ). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10 -6 ) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10 -6 to 5.24 × 10 -8 ). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10 -6 ). These results provide new insights into the pathogenesis and pathophysiology of KD.

Classification of coronary artery tissues using optical coherence tomography imaging in Kawasaki disease

NASA Astrophysics Data System (ADS)

Abdolmanafi, Atefeh; Prasad, Arpan Suravi; Duong, Luc; Dahdah, Nagib

2016-03-01

Intravascular imaging modalities, such as Optical Coherence Tomography (OCT) allow nowadays improving diagnosis, treatment, follow-up, and even prevention of coronary artery disease in the adult. OCT has been recently used in children following Kawasaki disease (KD), the most prevalent acquired coronary artery disease during childhood with devastating complications. The assessment of coronary artery layers with OCT and early detection of coronary sequelae secondary to KD is a promising tool for preventing myocardial infarction in this population. More importantly, OCT is promising for tissue quantification of the inner vessel wall, including neo intima luminal myofibroblast proliferation, calcification, and fibrous scar deposits. The goal of this study is to classify the coronary artery layers of OCT imaging obtained from a series of KD patients. Our approach is focused on developing a robust Random Forest classifier built on the idea of randomly selecting a subset of features at each node and based on second- and higher-order statistical texture analysis which estimates the gray-level spatial distribution of images by specifying the local features of each pixel and extracting the statistics from their distribution. The average classification accuracy for intima and media are 76.36% and 73.72% respectively. Random forest classifier with texture analysis promises for classification of coronary artery tissue.

Genetic epistasis between killer immunoglobulin-like receptors and human leukocyte antigens in Kawasaki disease susceptibility.

PubMed

Bossi, G; Mannarino, S; Pietrogrande, M C; Salice, P; Dellepiane, R M; Cremaschi, A L; Corana, G; Tozzo, A; Capittini, C; De Silvestri, A; Tinelli, C; Pasi, A; Martinetti, M

2015-10-01

Kawasaki disease (KD) is a pediatric acute multisystemic vasculitis complicated by development of coronary artery lesions. The breakthrough theory on KD etiopathogenesis points to pathogens/environmental factors triggered by northeastern wind coming from China. Natural Killer cells and T lymphocytes express the inhibitory/activating Killer Immunoglobulin-like Receptors (KIR) to elicit an immune response against pathogens by binding to human leukocyte antigens (HLA) class I epitopes. We first report on the role of KIR/HLA genetic epistasis in a sample of 100 Italian KD children. We genotyped KIR, HLA-A, HLA-B and HLA-C polymorphisms, and compared KD data with those from 270 Italian healthy donors. The HLA-A*11 ligand for KIR2DS2/2DS4/3DL2 was a KD susceptibility marker by itself (odds ratio (OR)=3.85, confidence interval (CI)=1.55-9.53, P=0.004). Although no epistasis between HLA-A*11 and KIR2DS2/S4 emerged, HLA-A*11 also engages KIR3DL2, a framework gene encoding for a pathogen sensor of CpG-oligodeoxynucleotides (CpG-ODN), and KD blood mononuclear cells are actually prone to pathogen CpG-ODN activation in the acute phase. Moreover, carriers of KIR2DS2/HLA-C1 and KIR2DL2/HLA-C1 were more frequent among KD, in keeping with data demonstrating the involvement of these HLA/KIR couples in autoimmune endothelial damage. The highest KD risk factor was observed among carriers of KIR2DL2 and two or more HLA ligands (OR=10.24, CI=1.87-56.28; P=0.007).

Fine specificities of natural regulatory T cells after IVIG therapy in patients with Kawasaki disease

PubMed Central

Burns, Jane C.; Touma, Ranim; Song, Yali; Padilla, Robert L.; Tremoulet, Adriana H.; Sidney, John; Sette, Alessandro; Franco, Alessandra

2016-01-01

The activation of natural regulatory T cells (nTreg) recognizing the heavy constant region (Fc) of IgG is an important mechanism of action of intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD). Lack of circulating Fc-specific nTreg in the sub-acute phase of KD is correlated with the development of coronary artery abnormalities (CAA). Here, we characterize the fine specificity of nTreg in sub-acute (2- to 8-week post-IVIG) and convalescent (1- to 10-year post-IVIG) KD subjects by testing the immunogenicity of 64 peptides, 15 amino acids in length with a 10 amino acid-overlap spanning the entire Fc protein. About 12 Fc peptides (6 pools of 2 consecutive peptides) were recognized by nTreg in the cohorts studied, including two patients with CAA. To test whether IVIG expands the same nTreg populations that maintain vascular homeostasis in healthy subjects, we compared these results with results obtained in healthy adult controls. Similar nTreg fine specificities were observed in KD patients after IVIG and in healthy donors. These results suggest that T cell fitness rather than T cell clonal deletion or anergy is responsible for the lack of Fc-specific nTreg in KD patients who develop CAA. Furthermore, we found that adolescents and adults who had KD during childhood without developing CAA did not respond to the Fc protein in vitro, suggesting that the nTreg response induced by IVIG in KD patients is short-lived. Our results support the concept that peptide epitopes may be a viable therapeutic approach to expand Fc-specific nTreg and more effectively prevent CAA in KD patients. PMID:25822882

Interface dermatitis in skin lesions of Kikuchi-Fujimoto's disease: a histopathological marker of evolution into systemic lupus erythematosus?

PubMed

Paradela, S; Lorenzo, J; Martínez-Gómez, W; Yebra-Pimentel, T; Valbuena, L; Fonseca, E

2008-12-01

Kikuchi's disease (KD) is a self-limiting histiocytic necrotizing lymphadenitis (HNL). Cutaneous manifestations are frequent and usually show histopathological findings similar to those observed in the involved lymph nodes. HNL with superposed histological features to KD has been described in patients with lupus erythematosus (LE), and a group of healthy patients previously reported as having HNL may evolve into LE after several months. Up to date, features to predict which HNL patients will have a self-limiting disease and which could develop LE have been not identified. In order to clarify the characteristics of skin lesions associated with KD, we report a case of HNL with evolution into systemic lupus erythematosus (SLE) and a review of previous reports of KD with cutaneous manifestations. A 17-year-old woman presented with a 4-month history of fever and generalised lymphadenopathy. A diagnosis of HNL was established based on a lymph node biopsy. One month later, she developed an erythematoedematous rash on her upper body, with histopathological findings of interface dermatitis. After 8 months, anti-nuclear antibodies (ANA) at titre of 1/320, anti-DNA-ds antibodies and marked decrease of complement levels were detected. During the following 2 years, she developed diagnostic criteria for SLE, with arthralgias, pleuritis, aseptic meningitis, haemolytic anaemia and lupus nephritis. To our knowledge, 27 cases of nodal and cutaneous KD have been reported, 9 of which later developed LE. In all these patients, the skin biopsy revealed interface dermatitis. Skin biopsy revealed a pattern of interface dermatitis in all reviewed KD cases, which evolved into LE. Even this histopathological finding was not previously considered significant; it might be a marker of evolution into LE.

[Giant coronary aneurysms in infants with Kawasaki disease].

PubMed

Sánchez Andrés, Antonio; Salvador Mercader, Inmaculada; Seller Moya, Julia; Carrasco Moreno, José Ignacio

2017-08-01

Kawasaki disease (KD) is an acute vasculitis of unknown origin and predominant in males. The long-term effects of the disease depend on whether there are coronary lesions, particularly aneurysms. The prognosis of patients with giant aneurysms is very poor due to their natural progression to coronary thrombosis or severe obstructive lesions. A series of 8 cases is presented where the epidemiology and diagnostic methods are described. The treatment of the acute and long-term cardiovascular sequelae is also reviewed. A descriptive analysis was conducted on patients admitted to the Paediatric Cardiology Unit of La Fe University Hospital (Valencia) with KD and a coronary lesion. More than one artery was involved in all patients. Although early diagnosis was established in only two cases, none of the patients had severe impairment of ventricular function during the acute phase. Treatment included intravenous gammaglobulin and acetylsalicylic acid at anti-inflammatory doses during the acute phase. A combination of dual antiplatelet therapy and corticosteroids was given in cases of coronary thrombosis. The silent aneurysms continue to persist. KD is the most common cause of acquired heart disease in children. The delay in diagnosis is associated with a greater likelihood of coronary lesions that could increase the risk of cardiovascular events in adulthood. Thus, this subgroup requires close clinical monitoring for a better control of cardiovascular risk factors over time. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

A numerical study of the 3-periodic wave solutions to KdV-type equations

NASA Astrophysics Data System (ADS)

Zhang, Yingnan; Hu, Xingbiao; Sun, Jianqing

2018-02-01

In this paper, by using the direct method of calculating periodic wave solutions proposed by Akira Nakamura, we present a numerical process to calculate the 3-periodic wave solutions to several KdV-type equations: the Korteweg-de Vries equation, the Sawada-Koterra equation, the Boussinesq equation, the Ito equation, the Hietarinta equation and the (2 + 1)-dimensional Kadomtsev-Petviashvili equation. Some detailed numerical examples are given to show the existence of the three-periodic wave solutions numerically.

Correlation of HAMP gene polymorphisms and expression with the susceptibility and length of hospital stays in Taiwanese children with Kawasaki disease

PubMed Central

Lu, Hsing-Fang; Wong, Henry Sung-Ching; Yu, Hong-Ren; Kuo, Hsing-Chun; Huang, Fu-Chen; Lo, Mao-Hung; Hsieh, Kai-Sheng; Chen, Su-Fen; Chang, Wei-Chiao; Kuo, Ho-Chang

2017-01-01

Kawasaki disease (KD) is a form of systemic vasculitis. Regarding its pathogenesis, HAMP gene encoding hepcidin, which is significant for iron metabolism, has a vital function. In this study, we recruited a total of 381 KD patients for genotyping. Data from 997 subjects (500 subjects from cohort 1; 497 subjects from cohort 2) were used for analysis. Using TaqMan allelic discrimination, we determined five tag SNPs (rs916145, rs10421768, rs3817623, rs7251432, and rs2293689). Treatment outcome data related to such clinical phenotypes as coronary artery lesions (CAL), coronary artery aneurysms (CAA), and intravenous immunoglobulin (IVIG) effects were also collected. Furthermore, we measured plasma hepcidin levels with an enzyme-linked immunosorbent assay. We found that HAMP gene polymorphism (rs7251432, and rs2293689) was significantly correlated with KD risk and that plasma hepcidin levels both before and after IVIG treatment had a significantly positive correlation with length of hospital stays (R = 0.217, p = 0.046 and R = 0.381, p < 0.0001, respectively). In contrast, plasma hepcidin levels has a negative correlation with KD patients’ albumin levels (R = −0.27, p < 0.001) prior to IVIG treatment. This study's findings indicate that HAMP might have a role in the disease susceptibility, as well as its expressions correlated length of hospital stays, and albumin levels in Taiwanese children with KD. PMID:28881695

[Clinical analysis of 942 cases of Kawasaki disease].

PubMed

Zhang, Wei; Li, Qiu; Zhao, Xiao-dong; Tang, Xue-mei; Wang, Xiao-gang; Wang, Mo; Wu, Dao-qi; Ou, Qian; Yang, Xi-qiang

2006-05-01

The study was designed to investigate the clinical characteristics and the effects of therapeutic proposal on Kawasaki disease (KD). Clinical features, diagnosis and treatment for totally 942 patients with KD hospitalized during Jan, 2000 to Dec, 2004 were reviewed. Clinical features of typical and incomplete KD were compared. Also, influential factors for KD resistant to intravenous immune globulin (IVIG) therapy were analyzed. Five hundred and ten cases were followed up for analyzing the prognosis of coronary artery lesion (CAL). (1) 774 cases were diagnosed as typical KD, and 168 cases as incomplete KD. The incidence of infants with incomplete KD was higher than that of infants with typical KD (18.5% vs. 10.1%, P < 0.01). As compared with typical KD, the cases of incomplete KD had a long duration of fever before final diagnosis [(7.7 +/- 2.9) d vs. (7.0 +/- 2.4) d, P < 0.01], high hemoglobin level [Hb, (106.6 +/- 13.4) g/L vs. (103.5 +/- 12.3) g/L, P < 0.01], high hematocrit [Hct, (32.0 +/- 4.3)% vs. (31.0 +/- 4.0)%, P < 0.01], and high prevalence of CAL (23.8% vs. 16.8%, P < 0.05), respectively. The occurrence rate and emerging time of clinical manifestations in incomplete KD and in typical KD were presented, respectively: non-exudative conjunctivitis [occurrence rate, 64.9% vs. 93.5%; emerging time, (4.4 +/- 1.4) d vs. (4.0 +/- 1.6) d, respectively (P < 0.05 or P < 0.01)], erythema and cracking of lips [occurrence rate, 50.6% vs. 94.8%; emerging time, (4.9 +/- 1.4) d vs. (4.5 +/- 1.6) d, respectively (P < 0.05 or P < 0.01)], rash [occurrence rate, 35.1% vs. 87.7%; emerging time, (3.9 +/- 1.9) d vs. (3.4 +/- 1.7) d, respectively (P < 0.05 or P < 0.01)], erythema and edema of extremity [occurrence rate, 26.8% vs. 71.4%; emerging time, (6.7 +/- 1.5) d vs. (5.3 +/- 1.7) d, respectively (P < 0.01)], cervical lymphadenopathy [occurrence rate, 34.5% vs. 68.0%; emerging time, (4.3 +/- 2.5) d vs. (3.6 +/- 2.2) d, respectively (P < 0.05 or P < 0.01)], strawberry tongue

Reducing process delays for real-time earthquake parameter estimation - An application of KD tree to large databases for Earthquake Early Warning

NASA Astrophysics Data System (ADS)

Yin, Lucy; Andrews, Jennifer; Heaton, Thomas

2018-05-01

Earthquake parameter estimations using nearest neighbor searching among a large database of observations can lead to reliable prediction results. However, in the real-time application of Earthquake Early Warning (EEW) systems, the accurate prediction using a large database is penalized by a significant delay in the processing time. We propose to use a multidimensional binary search tree (KD tree) data structure to organize large seismic databases to reduce the processing time in nearest neighbor search for predictions. We evaluated the performance of KD tree on the Gutenberg Algorithm, a database-searching algorithm for EEW. We constructed an offline test to predict peak ground motions using a database with feature sets of waveform filter-bank characteristics, and compare the results with the observed seismic parameters. We concluded that large database provides more accurate predictions of the ground motion information, such as peak ground acceleration, velocity, and displacement (PGA, PGV, PGD), than source parameters, such as hypocenter distance. Application of the KD tree search to organize the database reduced the average searching process by 85% time cost of the exhaustive method, allowing the method to be feasible for real-time implementation. The algorithm is straightforward and the results will reduce the overall time of warning delivery for EEW.

Kawasaki disease.

PubMed

Gouveia, Catarina; Brito, Maria João; Ferreira, Gonçalo Cordeiro; Ferreira, Manuel; Nunes, Maria Ana Sampaio; Machado, Maria do Céu

2005-09-01

Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed nations. Its incidence has risen in recent years and 20% of untreated patients develop coronary artery abnormalities. To analyze the epidemiological, clinical, laboratory and echocardiographic data of cases diagnosed in Hospital Fernando Fonseca and to identify factors that may influence prognosis. A retrospective study was performed of all children admitted to Hospital Fernando Fonseca with Kawasaki disease between June 1996 and December 2003. Diagnosis was based on the presence of fever plus four of the classic criteria or three of them in association with coronary aneurysms. Demographic and clinical features, laboratory and imaging findings, therapeutic measures and evolution were analyzed. SPSS for Windows was used for statistical analysis, applying the Mann-Whitney and Fisher's exact tests. A total of 23 children were admitted. The incidence was 8.2 per 100 000 children under 5. Their ages ranged from 6 months to five years (median 20 months). Half of the patients were aged < 2 years, and 21 (91%) were under 5. Most were male (74%) and white (83%). Nine children lived in the same area and ten (43%) had a concomitant infectious disease (parvovirus, Chlamydia pneumoniae, respiratory syncytial virus, enterovirus and herpesvirus 6). Twenty children had typical Kawasaki disease. Twenty-two received combined therapy with aspirin and high dose immunoglobulin, which was administered, on average, on the seventh day of the disease. Coronary disease was diagnosed in seven (30%) children. The frequency of cardiac lesions was highest in the youngest age group (< 2 years). The mean follow-up was 16 months. There was no mortality and aneurysmal changes persisted in only one patient. Cardiac disorders were more frequent in the youngest age group, as has been reported elsewhere. The common geographic origin and the evidence of several infectious agents suggest that infection may

Laboratory Biomarkers to Facilitate Differential Diagnosis between Measles and Kawasaki Disease in a Pediatric Emergency Room: A Retrospective Study.

PubMed

Buonsenso, Danilo; Macchiarulo, Giulia; Supino, Maria Chiara; La Penna, Francesco; Scateni, Simona; Marchesi, Alessandra; Reale, Antonino; Boccuzzi, Elena

2018-01-01

This retrospective study was conducted to analyze clinical and laboratoristic parameters to individuate specific differences and facilitate differential diagnosis between Measles and Kawasaki Disease (KD) at first evaluation in an emergency room. We found similar clinical features as duration of fever and number of KD criteria (p > 0.5) but significant differences in white blood cell count, neutrophils, CRP and LDH levels (p < 0.001). LDH value ≥ 800 mg/dl had sensibility of 89% and specificity of 90% for Measles while CRP ≥ 3 mg/dl had sensibility 89% and specificity of 85% for KD. The combined use of CRP, LDH and AST showed accuracy of 86.67%.

Hounsfield unit values of retropharyngeal abscess-like lesions seen in Kawasaki disease.

PubMed

Sasaki, Toru; Miyata, Rie; Hatai, Yoshiho; Makita, Kohzoh; Tsunoda, Koichi

2014-04-01

Retropharyngeal abscess-like lesions are occasionally seen in computed tomography (CT) imaging of patients with Kawasaki disease (KD) and these patients often undergo unnecessary surgery. We could distinguish the lesions from true abscesses by measuring their Hounsfield unit values (HUs). To distinguish the retropharyngeal abscess-like lesions from true abscesses without any surgical procedure. We investigated six cases of KD showing such lesions on CTs, both with and without contrast enhancement (CE). We measured the HUs of those lesions and compared them with those of 10 true abscesses as controls. Abscess-like lesions of KD were well enhanced by CE, whereas abscesses showed virtually no enhancement. The mean HU in the six KD cases was 20.0 ± 4.65 (mean ± SD) on plain CTs and 35.6 ± 4.49 on contrast CTs. In abscesses, it was 30.3 ± 4.42 on plain CTs and 30.3 ± 3.57 on contrast CTs. The difference in HU values [(HU on contrast CT) - (HU on plain CT)] was defined as ΔHU. The mean ΔHU was 15.6 ± 5.36 in the six KD lesions and 0.0 ± 2.93 in abscesses, with statistical significance of p < 0.0001 by Student's t test. Thus, ΔHU value may potentially be a useful parameter for their distinction.

Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases.

PubMed

Rödel, Franz; Fournier, Claudia; Wiedemann, Julia; Merz, Felicitas; Gaipl, Udo S; Frey, Benjamin; Keilholz, Ludwig; Seegenschmiedt, M Heinrich; Rödel, Claus; Hehlgans, Stephanie

2017-01-01

For decades, low- and moderate-dose radiation therapy (RT) has been shown to exert a beneficial therapeutic effect in a multitude of non-malignant conditions including painful degenerative muscoloskeletal and hyperproliferative disorders. Dupuytren and Ledderhose diseases are benign fibroproliferative diseases of the hand/foot with fibrotic nodules and fascial cords, which determine debilitating contractures and deformities of fingers/toes, while keloids are exuberant scar formations following burn damage, surgery, and trauma. Although RT has become an established and effective option in the management of these diseases, experimental studies to illustrate cellular composites and factors involved remain to be elucidated. More recent findings, however, indicate the involvement of radiation-sensitive targets like mitotic fibroblasts/myofibroblasts as well as inflammatory cells. Radiation-related molecular mechanisms affecting these target cells include the production of free radicals to hamper proliferative activity and interference with growth factors and cytokines. Moreover, an impairment of activated immune cells involved in both myofibroblast proliferative and inflammatory processes may further contribute to the clinical effects. We here aim at briefly describing mechanisms contributing to a modulation of proliferative and inflammatory processes and to summarize current concepts of treating hyperproliferative diseases by low and moderate doses of ionizing radiation.

Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified From Genome-Wide Association Study in Kawasaki Disease.

PubMed

Kuo, Ho-Chang; Wong, Henry Sung-Ching; Chang, Wei-Pin; Chen, Ben-Kuen; Wu, Mei-Shin; Yang, Kuender D; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Liu, Shih-Feng; Liu, Xiao; Chang, Wei-Chiao

2017-10-01

Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant. To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact P value 4.518×10 - 03 and 8.224×10 - 10 , respectively). This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG. © 2017 The Authors.

CFD-based Thrombotic Risk Assessment in Kawasaki Disease Patients with Coronary Artery Aneurysms

NASA Astrophysics Data System (ADS)

Sengupta, Dibyendu; Kung, Ethan; Kahn, Andrew; Burns, Jane; Marsden, Alison

2012-11-01

Coronary aneurysms occur in 25% of untreated Kawasaki Disease (KD) patients and put patients at increased risk for myocardial infarction and sudden death. Clinical guidelines recommend using aneurysm diameter >8 mm as the arbitrary criterion for treating with anti-coagulation therapy. This study uses patient-specific modeling to non-invasively determine hemodynamic parameters and quantify thrombotic risk. Anatomic models were constructed from CT angiographic image data from 5 KD aneurysm patients and one normal control. CFD simulations were performed to obtain hemodynamic data including WSS and particle residence times (PRT). Thrombosis was clinically observed in 4/9 aneurysmal coronaries. Thrombosed vessels required twice as many cardiac cycles (mean 8.2 vs. 4.2) for particles to exit, and had lower mean WSS (1.3 compared to 2.8 dynes/cm2) compared to vessels with non-thrombosed aneurysms of similar max diameter. 1 KD patient in the cohort with acute thrombosis had diameter < 8 mm. Regions of low WSS and high PRT predicted by simulations correlated with regions of subsequent thrombus formation. Thrombotic risk stratification for KD aneurysms may be improved by incorporating both hemodynamic and geometric quantities. Current clinical guidelines to assess patient risk based only on aneurysm diameter may be misleading. Further prospective study is warranted to evaluate the utility of patient-specific modeling in risk stratifying KD patients with coronary aneurysms. NIH R21.

Coronary artery aneurysm regression after Kawasaki disease and associated risk factors: a 3-year follow-up study in East China.

PubMed

Tang, Yunjia; Yan, Wenhua; Sun, Ling; Xu, Qiuqin; Ding, Yueyue; Lv, Haitao

2018-01-12

Kawasaki disease (KD) is the leading cause of acquired heart disease due to its complicated coronary artery lesions. Up to now, few studies were focused on the status of persistent coronary artery aneurysms (CAA) in KD patients. The present study was designed to identify the coronary artery outcomes and seek the risk factors associated with the regression of CAA in KD patients. One hundred and twenty KD patients with CAA hospitalized in Children's Hospital of Soochow University from Jan 2008 to Dec 2013 were prospectively studied by a 3-year follow-up. Data regarding demographic, clinical, laboratory, and echocardiographic characteristics were documented and further analyzed. It was estimated that 39.2% of the patients had complete regression of CAA within 4 weeks, 59.2% within 8 weeks, and 70.0% within 16 weeks. No fatal cardiac events occurred. We found patients who aged ≤ 1 year, received initial intravenous immunoglobulin (IVIG) treatment after the 10th day of illness, and IVIG non-responders were associated with the regression of persistent CAA. The relative risks were 1.55, 1.87, and 1.88, respectively. Age, initial IVIG treatment, and IVIG response were risk factors of persistent CAA, and more attention should be paid on these patients.

Peginterferon alfa‐2a (40KD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy

PubMed Central

Sherman, M; Yoshida, E M; Deschenes, M; Krajden, M; Bain, V G; Peltekian, K; Anderson, F; Kaita, K; Simonyi, S; Balshaw, R; Lee, S S

2006-01-01

Background The management of patients with chronic hepatitis C who have relapsed or failed to respond to interferon based therapies is an important issue facing hepatologists. Aims We evaluated the efficacy and safety of peginterferon alfa‐2a (40KD) plus ribavirin in this population by conducting a multicentre open label study. Patients Data from adults with detectable serum hepatitis C virus (HCV) RNA who had not responded or had relapsed after previous conventional interferon or conventional interferon/ribavirin combination therapy were analysed. Methods Patients were retreated with peginterferon alfa‐2a (40KD) 180 µg/week plus ribavirin 800 mg/day for 24 or 48 weeks at the investigators' discretion. The study was conceived before the optimal dose of ribavirin (1000/1200 mg/day) for patients with genotype 1 was known. The primary endpoint was sustained virological response (SVR), defined as undetectable HCV RNA (<50 IU/ml) after 24 weeks of follow up. The analysis was conducted by intention to treat. Results A total of 312 patients (212 non‐responders, 100 relapsers) were included. Of these, 28 patients were treated for 24 weeks and 284 for 48 weeks. Baseline characteristics between non‐responders and relapsers were similar although more non‐responders had genotype 1 infection (87% v 69%). Overall SVR rates were 23% (48/212) for non‐responders and 41% (41/100) for relapsers. When data were analysed by genotype, SVR rates were 24% (61/253) in genotype 1 and 47% (28/59) in genotype 2/3. Conclusions These results in a large patient cohort demonstrate that it is possible to cure a proportion of previous non‐responders and relapsers by retreating with peginterferon alfa‐2a (40KD) plus ribavirin. PMID:16709661

Silicone gel sheet dressing for sclerodermatous type chronic graftversus- host-disease (cGVHD).

PubMed

Dinçer, Süleyman L; Kargı, Eksal; Dinçer, Sibel; Fitoz, Filiz; Akan, Hamdi

2004-06-05

Systemic sclerosis is an autoimmune disease characterized by endothelial cell injury, fibroblast activation and immunological aberrations. Generalized form of the disease involves skin and other organs. Progressive sclerodermatous type cGVHD is the difficult type to treat. Immunosuppressors are the most commonly used treatment regimens. Topical silicone gel sheet (SGS) were first used in the treatment of burn wound and following their initial successes have begun to be used in the treatment of hypertrophic scars and keloids. To best of our knowledge, this is the first patient with extensive sclerodermatous type cGVHD in whom SGS was applied on to the skin of the antecubital region. After a six months application of SGS, the skin of this region was remarkably soft and thick compared to other regions of the arm. The result indicate that SGS may be an useful tool for the treatment of extensive sclerodermatous type cGVHD.

Clinical characteristics and serum N-terminal pro-brain natriuretic peptide as a diagnostic marker of Kawasaki disease in infants younger than 3 months of age.

PubMed

Bae, Hyun Kyung; Lee, Do Kyung; Kwon, Jung Hyun; Kim, Hae Soon; Sohn, Sejung; Hong, Young Mi

2014-08-01

The incidence of Kawasaki disease (KD) is rare in young infants (less than 3 months of age), who present with only a few symptoms that fulfill the clinical diagnostic criteria. The diagnosis for KD can therefore be delayed, leading to a high risk of cardiac complications. We examined the clinical characteristics and measured the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels of these patients for assessing its value in the early detection of KD. We retrospectively reviewed the data of young infants diagnosed with KD from 2004 to 2012. The control group included 20 hospitalized febrile patients. Laboratory data, including NT-proBNP were obtained for each patient in both groups. Incomplete KD was observed in 21/24 patients (87.5%). The mean fever duration on admission was 1.36±1.0 days in the KD group. Common symptoms included erythema at the site of Bacille Calmette-Guerin inoculation (70.8%), skin rash (50.0%), changes of oropharyngeal mucosa (29.1%), and cervical lymphadenopathy (20.8%). The mean number of major diagnostic criteria fulfilled was 2.8±1.4. Five KD patients (20.8%) had only one symptom matching these criteria. The incidence of coronary artery complications was 12.5%. The mean serum NT-proBNP level in the acute phase, in the KD and control groups, were 4,159±3,714 pg/mL and 957±902 pg/mL, respectively, which decreased significantly in the convalescent phase. Incomplete KD was observed in 87.5% patients. Serum NT-proBNP might be a valuable biomarker for the early detection of KD in febrile infants aged <3 months.

Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease

PubMed Central

Burns, Jane C.; Best, Brookie M.; Mejias, Asuncion; Mahony, Lynn; Fixler, David E.; Jafri, Hasan S.; Melish, Marian E.; Jackson, Mary Anne; Asmar, Basim I.; Lang, David J.; Connor, James D.; Capparelli, Edmund V.; Keen, Monica L.; Mamun, Khalid; Keenan, Gregory F.; Ramilo, Octavio

2010-01-01

Objective To test the safety, tolerability, and pharmacokinetics of the anti- TNF-α monoclonal antibody, infliximab, in subjects with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). Study design We conducted a multicenter, randomized, prospective trial of second IVIG infusion (2 g/kg) versus infliximab (5 mg/kg) in 24 children with acute KD and fever following initial treatment with IVIG. Primary outcome measures were infliximab safety, tolerability, and pharmacokinetics. Secondary outcome measures were duration of fever and changes in markers of inflammation. Results Study drug infusions were associated with cessation of fever within 24 hours in 11 of 12 subjects treated with infliximab and 8 of 12 subjects retreated with IVIG. No infusion reactions or serious adverse events were attributed to either study drug. No significant differences were observed between treatment groups in the change from baseline for laboratory variables, fever, or echocardiographic assessment of coronary arteries. Conclusion Both infliximab and a second IVIG infusion were safe and well-tolerated in subjects with KD who were resistant to standard IVIG treatment. The optimal management of patients resistant to IVIG remains to be determined. PMID:18672254

Proteomic analysis associated with coronary artery dilatation caused by Kawasaki disease using serum exosomes.

PubMed

Zhang, Li; Wang, Wei; Bai, Jun; Xu, Yu-Fen; Li, Lai-Qing; Hua, Liang; Deng, Li; Jia, Hong-Ling

2016-05-01

The aim of this study was to investigate the serum exosome proteome profile of coronary artery dilatation (CAD) caused by Kawasaki disease (KD). Two-dimensional electrophoresis was implemented on proteins of serum exosomes obtained from children with CAD caused by KD and from healthy controls. Differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry analysis. We identified 38 differentially expressed proteins (13 up-regulated and 25 down-regulated) from serum exosomes of patients with CAD caused by KD compared with healthy controls. Expression levels of three differentially expressed proteins (leucine-rich alpha-2-glycoprotein, sex hormone-binding globulin, and serotransferrin) were validated using western blot analysis. Classification and protein-protein network analysis showed that they are associated with multiple functional groups involved in the acute inflammatory response, defense response, complement activation, humoral immune response, and response to wounding. The majority of the proteins are involved in the inflammation and coagulation cascades. These findings establish a comprehensive proteome profile of CAD caused by KD and increase our knowledge of scientific insight into its mechanisms. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

N-terminal pro-B-type natriuretic peptide diagnostic algorithm versus American Heart Association algorithm for Kawasaki disease.

PubMed

Dionne, Audrey; Meloche-Dumas, Léamarie; Desjardins, Laurent; Turgeon, Jean; Saint-Cyr, Claire; Autmizguine, Julie; Spigelblatt, Linda; Fournier, Anne; Dahdah, Nagib

2017-03-01

Diagnosis of Kawasaki disease (KD) can be challenging in the absence of a confirmatory test or pathognomonic finding, especially when clinical criteria are incomplete. We recently proposed serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunctive diagnostic test. We retrospectively tested a new algorithm to help KD diagnosis based on NT-proBNP, coronary artery dilation (CAD) at onset, and abnormal serum albumin or C-reactive protein (CRP). The goal was to assess the performance of the algorithm and compare its performance with that of the 2004 American Heart Association (AHA)/American Academy of Pediatrics (AAP) algorithm. The algorithm was tested on 124 KD patients with NT-proBNP measured on admission at the present institutions between 2007 and 2013. Age at diagnosis was 3.4 ± 3.0 years, with a median of five diagnostic criteria; and 55 of the 124 patients (44%) had incomplete KD. CA complications occurred in 64 (52%), with aneurysm in 14 (11%). Using this algorithm, 120/124 (97%) were to be treated, based on high NT-proBNP alone for 79 (64%); on onset CAD for 14 (11%); and on high CRP or low albumin for 27 (22%). Using the AHA/AAP algorithm, 22/47 (47%) of the eligible patients with incomplete KD would not have been referred for treatment, compared with 3/55 (5%) with the NT-proBNP algorithm (P < 0.001). This NT-proBNP-based algorithm is efficient to identify and treat patients with KD, including those with incomplete KD. This study paves the way for a prospective validation trial of the algorithm. © 2016 Japan Pediatric Society.

Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson's disease.

PubMed

Cheng, Baohua; Yang, Xinxin; An, Liangxiang; Gao, Bo; Liu, Xia; Liu, Shuwei

2009-08-25

The high-fat ketogenic diet (KD) leads to an increase of blood ketone bodies (KB) level and has been used to treat refractory childhood seizures for over 80 years. Recent reports show that KD, KB and their components (d-beta-hydroxybutyrate, acetoacetate and acetone) have neuroprotective for acute and chronic neurological disorders. In our present work, we examined whether KD protected dopaminergic neurons of substantia nigra (SN) against 6-hydroxydopamine (6-OHDA) neurotoxicity in a rat model of Parkinson's disease (PD) using Nissl staining and tyrosine hydroxylase (TH) immunohistochemistry. At the same time we measured dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. To elucidate the mechanism, we also measured the level of glutathione (GSH) of striatum. Our data showed that Nissl and TH-positive neurons increased in rats fed with KD compared to rats with normal diet (ND) after intrastriatal 6-OHDA injection, so did DA and its metabolite DOPAC. While HVA had not changed significantly. The change of GSH was significantly similar to DA. We concluded that KD had neuroprotective against 6-OHDA neurotoxicity and in this period GSH played an important role.

Safety and immunogenicity of a freeze-dried, Vero cell culture-derived, inactivated Japanese encephalitis vaccine (KD-287, ENCEVAC®) versus a mouse brain-derived inactivated Japanese encephalitis vaccine in children: a phase III, multicenter, double-blinded, randomized trial.

PubMed

Yun, Ki Wook; Lee, Hoan Jong; Kang, Jin Han; Eun, Byung Wook; Kim, Yae-Jean; Kim, Kyung-Hyo; Kim, Nam Hee; Hong, Young Jin; Kim, Dong Ho; Kim, Hwang Min; Cha, Sung-Ho

2015-01-08

Although mouse brain-derived, inactivated Japanese encephalitis vaccines (JE-MBs) have been successfully used for a long time, potential rare neurological complications have prompted the development of a Vero cell culture-derived inactivated vaccine (JE-VC). In a phase III clinical study, we aimed to compare the safety and immunogenicity of a JE-VC, KD-287 with a JE-MB, JEV-GCC, in children. In this multicenter, double-blinded, randomized controlled trial, the study population consisted of 205 healthy Korean children aged 12-23 months. Each subject was subcutaneously vaccinated with either KD-287 or JEV-GCC twice at an interval of 2 weeks and then vaccinated once 12 months after the second vaccination. Neutralizing antibodies were measured by the plaque reduction neutralization test using the homologous and heterologous, as a post hoc analysis, challenge virus strains. The three-dose regimen of KD-287 showed a comparable safety profile with JEV-GCC except higher incidence of fever after the first dose (30.4% and 14.7%, respectively). Most of the fever was mild degree (61.3% and 66.7%, respectively). KD-287 fulfilled the non-inferiority criteria for seroconversion rate (SCR) and geometric mean titer (GMT) of the neutralizing antibody, which were the primary endpoints, at 4 weeks after the third vaccination (95% CI: -1.00, 3.10 for the SCR difference and 10.8, 17.6 for the GMT ratio). The SCRs of KD-287 were all 100% and the GMTs were higher in the KD-287 group than in the JEV-GCC group after the second vaccination and before and after the third vaccination (GMT ratio: 5.59, 20.13, and 13.79, respectively, p < 0.001 in all). GMTs were higher in the KD-287 group in the heterologous analysis also (GMT ratio: 4.05, 5.15, and 4.19, respectively, p < 0.001 in all). This study suggests that the KD-287, a JE-VC is as safe as and may be more effective than the licensed MB-derived vaccine. KD-287 could thus be useful as a second-generation vaccine and substitute

[Influence of cattle cord blood fraction below 5 kD on biochemical parameters of blood in experimental chronic stomach ulcer in rats].

PubMed

Gulevskiĭ, A K; Abakumova, E S; Moiseeva, N N; Dolgikh, O L

2008-01-01

Influence of cattle cord blood fraction (below 5 kD) on lipid peroxidation product content and alkaline phosphatase activity-in peripheral blood was studied on the experimental subchronic stomach ulcer model in rats. It has been shown that the fraction administrations normalize thiobarbituric-active product content and alkaline phosphatase activity in blood, which testifies to decreasing inflammatory reaction in the mucous membrane of the stomach. The fraction administrations accelerate the processes of regeneration of the mucous membrane of the stomach up to complete healing of ulcer defects. Cord blood fraction below 5 kD from cattle possesses antiulcer activity which is analogous to the actovegin activity. It has been shown by gel-penetrating chromatography that the pattern of cord blood fraction low molecular substances is different from the actovegin pattern both qualitatively and quantitatively.

The effect of FcγRIIA and FcγRIIB on coronary artery lesion formation and intravenous immunoglobulin treatment responses in children with Kawasaki disease

PubMed Central

Chang, Ling-Sai; Lo, Mao-Hung; Li, Sung-Chou; Yang, Ming-Yu; Hsieh, Kai-Sheng; Kuo, Ho-Chang

2017-01-01

Previous research has found patients with the FcγRIIIB NA1 variant having increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Our previous studies revealed that elevated FcγRIIA expression correlated with the susceptibility of KD patients. We conducted this research to determine whether and how Fcγ receptors affect the susceptibility, IVIG treatment response, and coronary artery lesions (CAL) of KD patients. The activating FcγRIIA and inhibitory FcγRIIB methylation levels of seven patients with KD and four control subjects were examined using HumanMethylation27 BeadChip. We enrolled a total of 44 KD patients and 10 control subjects with fevers. We performed real-time RT-PCR to determine the FcγRIIA and FcγRIIB expression levels, as well as a luciferase assay of FcγRIIA. We found a considerable increase in methylation of both FcγRIIA and FcγRIIB in KD patients undergoing IVIG treatment. Promoter methylation of FcγRIIA inhibited reporter activity in K562 cells using luciferase assay. The FcγRIIB mRNA expression levels were not found to increase susceptibility, CAL formation, or IVIG resistance. FcγRIIA mRNA expression levels were significantly higher in IVIG-resistant patients than in those that responded to IVIG during the pre-treatment period. Furthermore, the FcγRIIA/IIB mRNA expression ratio was considerably higher in KD patients with CAL than in those without CAL. FcγRIIA and FcγRIIB both demonstrated increased methylation levels in KD patients that underwent IVIG treatment. FcγRIIA expression influenced the IVIG treatment response of KD patients. The FcγRIIA/IIB mRNA expression ratio was greater in KD patients with CAL formation. PMID:27893416

Investigation of Kp- and Kd-atom formation and their collisional processes with hydrogen and deuterium targets by the classical-trajectory Monte Carlo method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raeisi, G. M.; Department of Physics, Shahrekord University, Shahrekord 115; Kalantari, S. Z.

The classical-trajectory Monte Carlo method has been used to study the capture of negative kaons by hydrogen and deuterium atoms; subsequently, the elastic scattering, Stark mixing, and Coulomb deexcitation cross sections of Kp and Kd atoms have been determined. The results for kaonic atom formation confirm the initial conditions that have been parametrically applied by most atomic cascade models. Our results show that Coulomb deexcitation in Kp and Kd atoms with {Delta}n>1 is important in addition to n=1. We have shown that the contribution of molecular structure effects to the cross sections of the collisional processes is larger than themore » isotopic effects of the targets. We have also compared our results with the semiclassical approaches.« less

Acute Kawasaki disease with emphasis on the echocardiographic profile: A single center experience

PubMed Central

Hamza, Hala S.; Zaher, Asmaa Z.; Agha, Hala M.

Background: Echocardiographic features of acute Kawasaki disease (KD) have not been well characterized in Egyptian children. This study aimed to provide insight into the pattern of cardiac involvement in Egyptian children with Kawasaki disease, focusing on echocardiographic coronary abnormalities and their associated risk predictors. Methods and Results: Medical records of 64 KD patients from 2012 to 2016 were retrospectively analyzed with recalculation of coronary artery z-scores during the first eight weeks after fever onset. All patients received intravenous immunoglobulin (IVIG) and 57.8% were treated within 10 days of illness onset. Coronary abnormalities were found in 53.1% of all patients, and in 43.2% of those who received IVIG within 10 days. Giant aneurysms (z-score>10) comprised 23.5% of all coronary abnormalities. Coronary thrombosis occurred in two patients (5%), both of whom developed myocardial infarction, and one succumbed to heart failure with eventual in-hospital death. Overall, 7% of patients had mitral regurgitation (n = 5), 1.5% had aortic regurgitation (n = 1), and 7.8% had pericardial effusion (n = 5). Among a number of laboratory and clinical predictors, platelet count had the strongest association with coronary abnormalities (Area under Receiver-operating characteristic (ROC) curve: 0.794; 95% confidence interval 0.678–0.910; P < 0.001). Conclusion: Coronary abnormalities occur in a substantial percentage of KD in Egypt, with associated evidence of severe inflammation. Further efforts are required to increase awareness of the disease and to emphasize the importance of early IVIG administration. Future studies should also be undertaken to characterize the long term progression profile of the disease as well as the possible genetic background of the disease in Egypt. PMID:29564348

Kimura's Disease without Peripheral Eosinophilia: An Unusual and Challenging Case Simulating Venous Malformation on Imaging Studies-Case Report and Review of literature.

PubMed

Dokania, Vivek; Patil, Digvijay; Agarwal, Ketan; Thakur, Prajakta; Prajapati, Piyush

2017-06-01

Kimura's Disease (KD) is a rare chronic inflammatory disorder presenting as multiple painless solitary subcutaneous nodules, predominantly in the head and neck region and frequently associated with regional lymphadenopathy and/or salivary gland involvement. Because of painless nature and indolent course, there is usually a delay in the patient's presentation. KD may radiologically mimic other chronic inflammatory conditions like tuberculosis, vascular malformations and neoplasms. Clinical correlation and histological evaluation along with elevated peripheral eosinophil and serum IgE level are considered important for confirmatory diagnosis. We report a case of painless swelling over right submandibular region extending to the right superficial parotid. The haematological reports were within normal limits. Ultrasound (USG), Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiogram (MRA) favoured a diagnosis of venous malformation. However, histopathological examination of excised lesion confirmed a diagnosis of KD. This case proves the possibility of the KD even in the absence of peripheral eosinophilia and/ or elevated serum IgE level, and may mimic venous malformation on imaging studies. Therefore, KD must find a place in the differentials of solitary painless neck swelling even in the absence of peripheral eosinophilia and/or elevated IgE level.

Acute kidney injury and cholestasis associated with Kawasaki disease in a 9-year-old: Case report.

PubMed

Martínez Vázquez, José Allan; Sánchez García, Carlos; Rodríguez Muñoz, Lorena; Martínez Ramírez, Rogelio Osvaldo

2017-12-15

Kawasaki disease (KD) is a systemic vasculitis frequent in children younger than 5 years of age. It involves coronary arteries and other medium-sized vessels. There also exists evidence of inflammatory and proliferative changes affecting the biliary tract and lymphocyte infiltration of the renal interstitial. We describe the case of a 9-year-old girl who developed high-grade fever, bilateral non-purulent conjunctivitis, «strawberry» tongue, desquamation of the fingers and toes, cholestatic syndrome, edema and elevated serum creatinine. KD is a diagnostic challenge for the pediatrician. In every patient with high-grade fever, cholestasis and acute kidney injury, KD should be included in the differential diagnosis, even though more research is necessary to evaluate this atypical association. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Carotid Intima-Media Thickness and Lipid Profile in Children With Kawasaki Disease: A Single-Center Follow-up Study After a Mean Duration of 6.9 Years.

PubMed

Gopalan, Kavitha; Singh, Surjit; Vignesh, Pandiarajan; Gupta, Anju; Rohit, Manojkumar; Attri, Savita Verma

2018-03-13

Kawasaki disease (KD) has a predilection to involve coronary arteries, leading to several long-term cardiovascular sequelae. Apart from coronary artery abnormalities, children with KD are also prone to develop premature atherosclerosis, endothelial dysfunction, and lipid abnormalities. Some of these complications may occur even in children who have received appropriate treatment with intravenous immunoglobulin in the acute phase. In 2009, we had studied carotid intima-media thickness (cIMT) and lipid profile in 27 children with KD at least 1 year after the acute episode. In the present study, we have followed up the same cohort of 27 children at least 5 years after the acute episode of KD. We measured the cIMT, a surrogate marker for premature atherosclerosis, and fasting lipid profile in the cohort and compared the results with values obtained in our previous study. There was significantly higher mean cIMT in children with KD as compared with control subjects. However, there was no significant difference in cIMT among children in the cohort at 1 and 5 years of follow-up. Abnormal lipid profile was seen in 7 of 27 children in the present study, 5 of whom also had had lipid abnormality at 1-year follow-up. This suggests that lipid abnormalities in KD may be long lasting. Children with KD need careful long-term follow-up even when they do not have overt and persistent coronary artery abnormalities. It is possible that consequences of KD in childhood may impact health status of young adults several years later.

a Gross Error Elimination Method for Point Cloud Data Based on Kd-Tree

NASA Astrophysics Data System (ADS)

Kang, Q.; Huang, G.; Yang, S.

2018-04-01

Point cloud data has been one type of widely used data sources in the field of remote sensing. Key steps of point cloud data's pro-processing focus on gross error elimination and quality control. Owing to the volume feature of point could data, existed gross error elimination methods need spend massive memory both in space and time. This paper employed a new method which based on Kd-tree algorithm to construct, k-nearest neighbor algorithm to search, settled appropriate threshold to determine with result turns out a judgement that whether target point is or not an outlier. Experimental results show that, our proposed algorithm will help to delete gross error in point cloud data and facilitate to decrease memory consumption, improve efficiency.

Hemodynamic simulations in coronary aneurysms of children with Kawasaki disease

NASA Astrophysics Data System (ADS)

Sengupta, Dibyendu; Burns, Jane; Marsden, Alison

2009-11-01

Kawasaki disease (KD) is a serious pediatric illness affecting the cardiovascular system. One of the most serious complications of KD, occurring in about 25% of untreated cases, is the formation of large aneurysms in the coronary arteries, which put patients at risk for myocardial infarction. In this project we performed patient specific computational simulations of blood flow in aneurysmal left and right coronary arteries of a KD patient to gain an understanding about their hemodynamics. Models were constructed from CT data using custom software. Typical pulsatile flow waveforms were applied at the model inlets, while resistance and RCR lumped models were applied and compared at the outlets. Simulated pressure waveforms compared well with typical physiologic data. High wall shear stress values are found in the narrow region at the base of the aneurysm and low shear values occur in regions of recirculation. A Lagrangian approach has been adopted to perform particle tracking and compute particle residence time in the recirculation. Our long-term goal will be to develop links between hemodynamics and the risk for thrombus formation in order to assist in clinical decision-making.

Atherosclerotic Cardiovascular Disease Beginning in Childhood

PubMed Central

2010-01-01

Although the clinical manifestations of cardiovascular disease (CVD), such as myocardial infarction, stroke, and peripheral vascular disease, appear from middle age, the process of atherosclerosis can begin early in childhood. The early stage and progression of atherosclerosis in youth are influenced by risk factors that include obesity, hypertension, dyslipidemia, and smoking, and by the presence of specific diseases, such as diabetes mellitus and Kawasaki disease (KD). The existing evidence indicates that primary prevention of atherosclerotic disease should begin in childhood. Identification of children at risk for atherosclerosis may allow early intervention to decrease the atherosclerotic process, thereby preventing or delaying CVD. This review will describe the origin and progression of atherosclerosis in childhood, and the identification and management of known risk factors for atherosclerotic CVD in children and young adults. PMID:20111646

Nova Sco 2016 No. 2 = PNV J17225112-3158349 = ASASSN-16kd

NASA Astrophysics Data System (ADS)

Waagen, Elizabeth O.

2016-09-01

AAVSO Alert Notice 550 announces the independent discovery of Nova Sco 2016 No. 2 = ASASSN-16kd = PNV J17225112-3158349 = V1656 Sco by Shigehisa Fujikawa (Kan'onji, Kagawa, Japan) at unfiltered CCD magnitude 11.6 on 2016 September 06.481 UT; and by ASAS-SN (Stanek et al., ATel #9469) at 12.13 V on 2016 September 06.00 UT. Spectroscopy indicating that Nova Sco 2016 No. 2 is a highly reddened classical Fe II-type nova was obtained by Arai and Honda (CBET 4320); by Bohlsen (ATel #9477); by Bersier et al. (ATel #9478); and by Prieto et al. (ATel #9479). Finder charts with sequence may be created using the AAVSO Variable Star Plotter (https://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details.

Stability properties of solitary waves for fractional KdV and BBM equations

NASA Astrophysics Data System (ADS)

Angulo Pava, Jaime

2018-03-01

This paper sheds new light on the stability properties of solitary wave solutions associated with Korteweg-de Vries-type models when the dispersion is very low. Using a compact, analytic approach and asymptotic perturbation theory, we establish sufficient conditions for the existence of exponentially growing solutions to the linearized problem and so a criterium of spectral instability of solitary waves is obtained for both models. Moreover, the nonlinear stability and spectral instability of the ground state solutions for both models is obtained for some specific regimen of parameters. Via a Lyapunov strategy and a variational analysis, we obtain the stability of the blow-up of solitary waves for the critical fractional KdV equation. The arguments presented in this investigation show promise for use in the study of the instability of traveling wave solutions of other nonlinear evolution equations.

F-Expansion Method and New Exact Solutions of the Schrödinger-KdV Equation

PubMed Central

Filiz, Ali; Ekici, Mehmet; Sonmezoglu, Abdullah

2014-01-01

F-expansion method is proposed to seek exact solutions of nonlinear evolution equations. With the aid of symbolic computation, we choose the Schrödinger-KdV equation with a source to illustrate the validity and advantages of the proposed method. A number of Jacobi-elliptic function solutions are obtained including the Weierstrass-elliptic function solutions. When the modulus m of Jacobi-elliptic function approaches to 1 and 0, soliton-like solutions and trigonometric-function solutions are also obtained, respectively. The proposed method is a straightforward, short, promising, and powerful method for the nonlinear evolution equations in mathematical physics. PMID:24672327

F-expansion method and new exact solutions of the Schrödinger-KdV equation.

PubMed

Filiz, Ali; Ekici, Mehmet; Sonmezoglu, Abdullah

2014-01-01

F-expansion method is proposed to seek exact solutions of nonlinear evolution equations. With the aid of symbolic computation, we choose the Schrödinger-KdV equation with a source to illustrate the validity and advantages of the proposed method. A number of Jacobi-elliptic function solutions are obtained including the Weierstrass-elliptic function solutions. When the modulus m of Jacobi-elliptic function approaches to 1 and 0, soliton-like solutions and trigonometric-function solutions are also obtained, respectively. The proposed method is a straightforward, short, promising, and powerful method for the nonlinear evolution equations in mathematical physics.

Determination of the distribution coefficient (log Kd) of oxytetracycline, tylosin A, olaquindox and metronidazole in manure.

PubMed

Loke, Marie-Louise; Tjørnelund, Jette; Halling-Sørensen, Bent

2002-07-01

Olaquindox (log Kow = -2.3) and metronidazole (log Kow = -0.1) both have low tendencies to sorp to particles in manure. This corresponds with the negative log Kow values of these antibiotics. Tylosin (log Kow = 1.63) and oxytetracycline (log Kow = -1.12) sorp relatively strongly to the manure particles and have log Kd values between 1.5 and 2.0. The tendency to bind to manure was ranked after increasing binding as follows: metronidazole < olaquindox < tylosin A and oxytetracycline. This order of ranking is consistent with results of sorption in soil. Our experiments illustrate that for some antibacterial agents estimation of the partitioning coefficients, Kd, cannot be made from Kow and f(oc) alone. Sorption of oxytetracycline to manure is much higher than expected from the negative log Kow value of the compound. It is believed that sorption of oxytetracycline to manure is influenced by ionic binding to divalent metal ions as such Mg2+ and Ca2+ as well as other charged compounds in the matrix. Binding of oxytetracycline to soil is stronger than the binding to manure. This is most likely due to the strong mineral related metal complexes formed between soil, metal ion and oxytetracycline. These complexes are not known to exist in manure. The relatively strong sorption of tylosin A to manure corresponds with data found for soil sorption of tylosin. Tylosin has a log Kow value of 2.5, thus it is not surprising that this drug binds strongly to manure.

Characteristics and Fate of Systemic Artery Aneurysm after Kawasaki Disease.

PubMed

Hoshino, Shinsuke; Tsuda, Etsuko; Yamada, Osamu

2015-07-01

To determine the long-term outcome of systemic artery aneurysms (SAAs) after Kawasaki disease (KD). We investigated the characteristics and the fate of SAAs in 20 patients using medical records and angiograms. The age of onset of KD ranged from 1 month to 20 months. The interval from the onset of KD to the latest angiogram ranged from 16 months to 24 years. The regression rate of peripheral artery aneurysm and the frequency of stenotic lesions were analyzed by the Kaplan-Meier method in 11 patients who had undergone initial angiography within 4 months. The mean duration of fever was 24 ± 12 days. All 20 patients had at least 1 symmetric pair of aneurysms in bilateral peripheral arteries, and 16 patients had multiple SAAs. The distributions of SAAs was as follows: brachial artery, 30; common iliac artery, 20; internal iliac artery, 21; abdominal aortic aneurysm, 7; and others, 29. The frequencies of regression of SAA and of the occurrence of stenotic lesions at 20 years after the onset of KD were 51% and 25%, respectively (n = 42). The diameter of all SAAs in the acute phase leading to stenotic lesions in the late period was >10 mm. SAAs occurred symmetrically and were multiple in younger infants and those with severe acute vasculitis. The fate of SAAs resembles that of coronary artery aneurysms, and depends on the diameter during the acute phase. Larger SAAs can lead to stenotic lesions in the late period. Copyright © 2015 Elsevier Inc. All rights reserved.

Associations Between Selenium Content in Hair and Kashin-Beck Disease/Keshan Disease in Children in Northwestern China: a Prospective Cohort Study.

PubMed

Liu, Huan; Yu, Fangfang; Shao, Wanzhen; Ding, Dexiu; Yu, Zhidao; Chen, Fengshi; Geng, Dong; Tan, Xiwang; Lammi, Mikko J; Guo, Xiong

2018-07-01

The objective of this study was to investigate the relationship between selenium content in hair and the incidence of Kashin-Beck disease (KBD) and Keshan disease (KD) in China. A prospective cohort study was conducted among children aged 5-12 years with different levels of low-selenium (group 1, Se ≤ 110 ng/g; group 2, 110 < Se ≤ 150 ng/g; and group 3, 150 < Se ≤ 200 ng/g) or selenium-supplemented (group 4, Se > 200 ng/g) exposure. A person-years approach was used to calculate the incidence and rate of positive clinical signs. Relative risk (RR), attributable risk, and etiologic fraction were used to determine the strength of association between selenium and disease incidence. Seven new KBD cases were diagnosed during 3-year follow-up. Positive clinical signs of KBD were found in 17.78 (95% confidence interval [CI] 14.27-21.29) cases per 100 person-years in group 1, 13.28 (9.82-16.74) in group 2, 12.95 (9.34-16.56) in group 3, and 8.18 (5.50-10.85) in group 4. Compared with group 4, the RR (95% CI) of groups 1, 2, and 3 were 2.17 (1.48-3.19), 1.62 (1.07-2.47), and 1.58 (1.03-2.43), respectively. Positive clinical signs of KD were 25.90 (18.62-33.18) cases per 100 person-years in group 1, 5.66 (1.26-10.06) in group 2, 4.60 (0.20-9.00) in group 3, and 14.62 (8.54-20.69) in group 4. Compared with group 4, the RR (95% CI) were 1.77 (1.07-2.93), 0.39 (0.16-0.93), and 0.31 (0.11-0.89), respectively. In children, the onset of KBD was negatively correlated with selenium content within a certain range. However, there may be a U-shaped association between selenium content and KD in children.

A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease.

PubMed

Van der Auwera, Ingrid; Wera, Stefaan; Van Leuven, Fred; Henderson, Samuel T

2005-10-17

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily strikes the elderly. Studies in both humans and animal models have linked the consumption of cholesterol and saturated fats with amyloid-beta (Abeta) deposition and development of AD. Yet, these studies did not examine high fat diets in combination with reduced carbohydrate intake. Here we tested the effect of a high saturated fat/low carbohydrate diet on a transgenic mouse model of AD. Starting at three months of age, two groups of female transgenic mice carrying the "London" APP mutation (APP/V717I) were fed either, a standard diet (SD) composed of high carbohydrate/low fat chow, or a ketogenic diet (KD) composed of very low carbohydrate/high saturated fat chow for 43 days. Animals fed the KD exhibited greatly elevated serum ketone body levels, as measured by beta-hydroxybutyrate (3.85 +/- 2.6 mM), compared to SD fed animals (0.29 +/- 0.06 mM). In addition, animals fed the KD lost body weight (SD 22.2 +/- 0.6 g vs. KD 17.5 +/- 1.4 g, p = 0.0067). In contrast to earlier studies, the brief KD feeding regime significantly reduced total brain Abeta levels by approximately 25%. Despite changes in ketone levels, body weight, and Abeta levels, the KD diet did not alter behavioral measures. Previous studies have suggested that diets rich in cholesterol and saturated fats increased the deposition of Abeta and the risk of developing AD. Here we demonstrate that a diet rich in saturated fats and low in carbohydrates can actually reduce levels of Abeta. Therefore, dietary strategies aimed at reducing Abeta levels should take into account interactions of dietary components and the metabolic outcomes, in particular, levels of carbohydrates, total calories, and presence of ketone bodies should be considered.

Modeling Transport of Cesium in Grimsel Granodiorite With Micrometer Scale Heterogeneities and Dynamic Update of Kd

NASA Astrophysics Data System (ADS)

Voutilainen, Mikko; Kekäläinen, Pekka; Siitari-Kauppi, Marja; Sardini, Paul; Muuri, Eveliina; Timonen, Jussi; Martin, Andrew

2017-11-01

Transport and retardation of cesium in Grimsel granodiorite taking into account heterogeneity of mineral and pore structure was studied using rock samples overcored from an in situ diffusion test at the Grimsel Test Site. The field test was part of the Long-Term Diffusion (LTD) project designed to characterize retardation properties (diffusion and distribution coefficients) under in situ conditions. Results of the LTD experiment for cesium showed that in-diffusion profiles and spatial concentration distributions were strongly influenced by the heterogeneous pore structure and mineral distribution. In order to study the effect of heterogeneity on the in-diffusion profile and spatial concentration distribution, a Time Domain Random Walk (TDRW) method was applied along with a feature for modeling chemical sorption in geological materials. A heterogeneous mineral structure of Grimsel granodiorite was constructed using X-ray microcomputed tomography (X-μCT) and the map was linked to previous results for mineral specific porosities and distribution coefficients (Kd) that were determined using C-14-PMMA autoradiography and batch sorption experiments, respectively. After this the heterogeneous structure contains information on local porosity and Kd in 3-D. It was found that the heterogeneity of the mineral structure on the micrometer scale affects significantly the diffusion and sorption of cesium in Grimsel granodiorite at the centimeter scale. Furthermore, the modeled in-diffusion profiles and spatial concentration distributions show similar shape and pattern to those from the LTD experiment. It was concluded that the use of detailed structure characterization and quantitative data on heterogeneity can significantly improve the interpretation and evaluation of transport experiments.

Analysis of factors associated with development of Bacille Calmette-Guérin inoculation site change in patients with Kawasaki disease.

PubMed

Araki, Tooru; Kodera, Aya; Kitada, Kunimi; Fujiwara, Michimasa; Muraoka, Michiko; Abe, Yoshiko; Ikeda, Masanori; Tsukahara, Hirokazu

2018-04-01

Objective The present study was performed to identify factors associated with a Bacille Calmette-Guérin (BCG) inoculation site change in patients with Kawasaki disease (KD). Methods Among patients who had received BCG vaccination and treatment for KD at our hospital from 2005 through 2016, 177 patients born in 2005 through 2016 were enrolled. The patients were divided into those with (n = 83, change group) and without (n = 94, no-change group) a BCG site change, and the patient demographics, clinical severity, blood examination results, and echocardiographic findings were compared between the two groups. Results The change group was younger at onset and had a shorter interval from vaccination to onset. A BCG site change was observed in patients who developed the onset of KD symptoms from 31 to 806 days after BCG vaccination. Multivariate analysis showed that the interval from vaccination was closely and positively associated with the BCG site change (hazard ratio = 0.995, 95% confidence interval = 0.993-0.997). Conclusion A BCG site change in patients with KD is most closely associated with the interval from BCG vaccination to onset.

Mid-term Risk for Subclinical Atherosclerosis and Chronic Myocarditis in Children with Kawasaki Disease and Transient Coronary Abnormalities.

PubMed

Parihar, Mansingh; Singh, Surjit; Vignesh, Pandiarajan; Gupta, Anju; Rohit, Manojkumar

2017-08-01

There is evidence for premature atherosclerosis and systemic arterial stiffening during follow-up of children with Kawasaki disease (KD) and coronary artery abnormalities (CAA). Moreover, patients with KD may also have subclinical myocardial involvement and inhomogeneous ventricular repolarization. The inhomogeneous ventricular repolarization manifests as increased QT dispersion on electrocardiography. There is a paucity of studies in endothelial dysfunction and QT dispersion in children with KD and transient CAA. Twenty children with KD and transient CAA were studied at least 1 year after resolution of CAA. Mean follow-up period between KD onset and enrolment in the study was 53.7 months. Twenty age and sex-matched controls were enrolled. High-resolution B-mode ultrasonography was used to analyze brachial artery dilatation in response to reactive hyperemia (cases and controls) and sublingual nitroglycerine (cases only). Carotid artery intima-media thickness (cIMT) and stiffness index were calculated. The difference between maximum and minimum QTc intervals on 12 lead electrocardiogram was calculated as QTc dispersion (QTcd). No statistically significant difference was noted in percent flow-mediated dilatation of brachial arteries in response to reactive hyperemia between cases (13.31 ± 10.41%) and controls (12.86 ± 7.09%). Sublingual nitroglycerine-mediated dilatation in children with KD was 14.88 ± 12.03%. Mean cIMT was similar in cases (0.036 ± 0.015 cm) and controls (0.035 ± 0.076 cm; p = 0.791). No statistically significant difference between groups was observed in mean QTcd values (0.057 ± 0.018 s vs. 0.059 ± 0.015 s in controls, p = 0.785). No evidence of significant endothelial dysfunction or increased QT dispersion in patients with KD and transient coronary artery abnormalities was found in our cohort when studied at a mean follow-up of 53.7 months. This is reassuring, and indicates that risk of subclinical atherosclerosis

Suppression of the rice fatty-acid desaturase gene OsSSI2 enhances resistance to blast and leaf blight diseases in rice.

PubMed

Jiang, Chang-Jie; Shimono, Masaki; Maeda, Satoru; Inoue, Haruhiko; Mori, Masaki; Hasegawa, Morifumi; Sugano, Shoji; Takatsuji, Hiroshi

2009-07-01

Fatty acids and their derivatives play important signaling roles in plant defense responses. It has been shown that suppressing a gene for stearoyl acyl carrier protein fatty-acid desaturase (SACPD) enhances the resistance of Arabidopsis (SSI2) and soybean to multiple pathogens. In this study, we present functional analyses of a rice homolog of SSI2 (OsSSI2) in disease resistance of rice plants. A transposon insertion mutation (Osssi2-Tos17) and RNAi-mediated knockdown of OsSSI2 (OsSSI2-kd) reduced the oleic acid (18:1) level and increased that of stearic acid (18:0), indicating that OsSSI2 is responsible for fatty-acid desaturase activity. These plants displayed spontaneous lesion formation in leaf blades, retarded growth, slight increase in endogenous free salicylic acid (SA) levels, and SA/benzothiadiazole (BTH)-specific inducible genes, including WRKY45, a key regulator of SA/BTH-induced resistance, in rice. Moreover, the OsSSI2-kd plants showed markedly enhanced resistance to the blast fungus Magnaporthe grisea and leaf-blight bacteria Xanthomonas oryzae pv. oryzae. These results suggest that OsSSI2 is involved in the negative regulation of defense responses in rice, as are its Arabidopsis and soybean counterparts. Microarray analyses identified 406 genes that were differentially expressed (>or=2-fold) in OsSSI2-kd rice plants compared with wild-type rice and, of these, approximately 39% were BTH responsive. Taken together, our results suggest that induction of SA-responsive genes, including WRKY45, is likely responsible for enhanced disease resistance in OsSSI2-kd rice plants.

Use of Lagrangian transport models and Sterilized High Volume Sampling to pinpoint the source region of Kawasaki disease and determine the etiologic agent

NASA Astrophysics Data System (ADS)

Curcoll Masanes, Roger; Rodó, Xavier; Anton, Jordi; Ballester, Joan; Jornet, Albert; Nofuentes, Manel; Sanchez-Manubens, Judith; Morguí, Josep-Anton

2015-04-01

Kawasaki disease (KD) is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 years. A former study [Rodó et al. 2011] demonstrated that certain patterns of winds in the troposphere above the earth's surface flowing from Asia were associated with the times of the annual peak in KD cases and with days having anomalously high numbers of KD patients. In a later study [Rodó et al. 2014], we used residence times from an Air Transport Model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. In order to cope with stationarity of synoptic situations, only trajectories for the winter months, when there is the maximum in KD cases, were considered. Trajectories traced back in time 10 days for each dataset and location were generated using the flexible particle Lagrangian dispersion model (FLEXPART Version 8.23 [Stohl et al. 2005]) run in backward mode. The particles modeled were air tracers, with 10,000 particles used on each model run. The model output used was residence time, with an output grid of 0.5° latitude × longitude and a time resolution of 3 h. The data input used for the FLEXPART model was gridded atmospheric wind velocity from the European Center for Medium-Range Weather Forecasts Re-Analysis (ERA-Interim at 1°). Aggregates of winter period back-trajectories were calculated for three different regions of Japan. A common source of wind air masses was located for periods with High Kawasaki disease. Knowing the trajectories of winds from the air transport models, a sampling methodology was developed in order to capture the possible etiological agent or other tracers that could have been released together. This methodology is based on the sterilized filtering of high volumes of the transported air at medium tropospheric levels by aircraft sampling and a later analyze these filters with adequate techniques. High purity

Association of FCGR2A rs1801274 polymorphism with susceptibility to autoimmune diseases: A meta-analysis.

PubMed

Zhang, Chang'e; Wang, Wenju; Zhang, Hong'e; Wei, Lulu; Guo, Shuping

2016-06-28

The aim of this meta-analysis was to estimate the association between the FCGR2A rs1801274 polymorphism and the susceptibility to autoimmune diseases more precisely. A meta-analysis was conducted on the association between the FCGR2A gene variants and ADs by allelic contrast, homozygote contrast, the recessive model, and the dominant model. A total of 17 studies with 30 comparisons in different populations and genotype-methods were available for this meta-analysis, including 10 Kawasaki disease (KD), 7 Ulcerative colitis (UC), 6 Crohn's disease (CD), 3 Rheumatoid arthritis (RA), 2 Systemic lupus erythematosus (SLE), 1 Autoimmune thyroid disease (ATD) and 1 diabetes mellitus type 1 (T1D). A significant association between FCGR2A rs1801274 polymorphism were found in KD (OR = 1.409, P < 0.001) and UC (OR = 1.237, P < 0.001). A overall meta-analysis increased risk of AD significant association between FCGR2A rs1801274 gene polymorphism and ADs under allelic (OR = 1.378, P=0.000), homozygous (OR: 1.866, P=0.001), dominant (OR = 1.667, P = 0.000) and recessive (OR = 1.434, P=0.000) in Asian population. Meanwhile, a decreased risk of AD was detected in the allelic (OR= 0.882, P = 0.011), homozygous (OR = 0.777, P = 0.013), dominant (OR = 0.850, P = 0.032) and recessive (OR = 0.840, P = 0.048) in African-American population. This meta-analysis demonstrates that the FCGR2A rs1801274 G-allele confers susceptibility to KD and UC. Data also suggests that the FCGR2A rs1801274 polymorphism may be associated with the susceptibility of multiple ADs in Asian and African-American populations.

Association of FCGR2A rs1801274 polymorphism with susceptibility to autoimmune diseases: A meta-analysis

PubMed Central

Wei, Lulu; Guo, Shuping

2016-01-01

Objectives The aim of this meta-analysis was to estimate the association between the FCGR2A rs1801274 polymorphism and the susceptibility to autoimmune diseases more precisely. Methods A meta-analysis was conducted on the association between the FCGR2A gene variants and ADs by allelic contrast, homozygote contrast, the recessive model, and the dominant model. Results A total of 17 studies with 30 comparisons in different populations and genotype-methods were available for this meta-analysis, including 10 Kawasaki disease (KD), 7 Ulcerative colitis (UC), 6 Crohn's disease (CD), 3 Rheumatoid arthritis (RA), 2 Systemic lupus erythematosus (SLE), 1 Autoimmune thyroid disease (ATD) and 1 diabetes mellitus type 1 (T1D). A significant association between FCGR2A rs1801274 polymorphism were found in KD (OR = 1.409, P < 0.001) and UC (OR = 1.237, P < 0.001). A overall meta-analysis increased risk of AD significant association between FCGR2A rs1801274 gene polymorphism and ADs under allelic (OR = 1.378, P=0.000), homozygous (OR: 1.866, P=0.001), dominant (OR = 1.667, P = 0.000) and recessive (OR = 1.434, P=0.000) in Asian population. Meanwhile, a decreased risk of AD was detected in the allelic (OR= 0.882, P = 0.011), homozygous (OR = 0.777, P = 0.013), dominant (OR = 0.850, P = 0.032) and recessive (OR = 0.840, P = 0.048) in African-American population. Conclusions This meta-analysis demonstrates that the FCGR2A rs1801274 G-allele confers susceptibility to KD and UC. Data also suggests that the FCGR2A rs1801274 polymorphism may be associated with the susceptibility of multiple ADs in Asian and African-American populations. PMID:27270653

Effectiveness of vasopressin V2 receptor antagonists OPC-31260 and OPC-41061 on polycystic kidney disease development in the PCK rat.

PubMed

Wang, Xiaofang; Gattone, Vincent; Harris, Peter C; Torres, Vicente E

2005-04-01

cAMP plays a major role in cystogenesis. Recent in vitro studies suggested that cAMP stimulates B-Raf/ERK activation and proliferation of cyst-derived cells in a Ca(2+) inhibitable, Ras-dependent manner. OPC-31260, a vasopressin V2 receptor (VPV2) antagonist, was shown to lower renal cAMP and inhibit renal disease development and progression in models orthologous to human cystic diseases. Here it is shown that OPC-41061, an antagonist chosen for its potency and selectivity for human VPV2, is effective in PCK rats. PCK kidneys have increased Ras-GTP and phosphorylated ERK levels and 95-kD/68-kD B-Raf ratios, changes that are corrected by the administration of OPC-31260 or OPC-41061. These results support the importance of cAMP in the pathogenesis of polycystic kidney disease, confirm the effectiveness of a VPV2 antagonist to be used in clinical trials for this disease, and suggest that OPC-31260 and OPC-41061 inhibit Ras/mitogen-activated protein kinase signaling in polycystic kidneys.

A peptide sequence on carcinoembryonic antigen binds to a 80kD protein on Kupffer cells.

PubMed

Thomas, P; Petrick, A T; Toth, C A; Fox, E S; Elting, J J; Steele, G

1992-10-30

Clearance of carcinoembryonic antigen (CEA) from the circulation is by binding to Kupffer cells in the liver. We have shown that CEA binding to Kupffer cells occurs via a peptide sequence YPELPK representing amino acids 107-112 of the CEA sequence. This peptide sequence is located in the region between the N-terminal and the first immunoglobulin like loop domain. Using native CEA and peptides containing this sequence complexed with a heterobifunctional crosslinking agent and ligand blotting with biotinylated CEA and NCA we have shown binding to an 80kD protein on the Kupffer cell surface. This binding protein may be important in the development of hepatic metastases.

Human herpes virus type 6 can cause skin lesions at the BCG inoculation site similar to Kawasaki Disease.

PubMed

Kakisaka, Yosuke; Ohara, Tomoichiro; Katayama, Saori; Suzuki, Tasuku; Sasai, Shu; Hino-Fukuyo, Naomi; Kure, Shigeo

2012-12-01

Kawasaki Disease (KD) is acute, febrile, multisystem vasculitis of early childhood, the detailed mechanism of which is still unclear. Skin symptoms occur in KD, such as edema of the hands and feet with subsequent desquamation and redness at the inoculation site of bacillus Calmette-Guerin (BCG). The change at the BCG inoculation site has been considered as a specific feature of KD, although its mechanism is not fully understood. We present an 11-month-old boy who developed fever with redness of the BCG site due to infection with human herpes virus type 6 (HHV6). At the age of 3 months, the patient received BCG. His fever remitted 7 days after the onset of skin redness, with sequential desquamation at the BCG site and extremities, which is not a common feature of HHV6 infection that typically lasts for 3 days. The final diagnosis was exanthema subitum. Characteristically, the HHV6 infection in our patient appeared to be associated with the invigoration of the T cell system, as represented by the elevated serum levels of soluble interleukin-2 receptor (3,490 U/ml vs. normal range 145-519 U/ml). This patient clearly showed redness and crusting at the BCG inoculation site, suggesting that HHV6 infection might cause skin changes similar to those of KD via an unknown mechanism. In addition, we suggest that the activation of the T cell system may account for the skin lesions in KD, characterized by redness and subsequent crusting of the BCG inoculation site and desquamation of the extremities.

Juvenile polyarteritis nodosa associated with toxoplasmosis presenting as Kawasaki disease.

PubMed

Başaran, Özge; Çakar, Nilgün; Gür, Gökçe; Kocabaş, Abdullah; Gülhan, Belgin; Çaycı, Fatma Şemsa; Çelikel, Banu Acar

2014-04-01

Polyarteritis nodosa (PAN) is a vasculitis characterized by inflammatory necrosis of medium-sized arteries. Juvenile PAN and Kawasaki disease (KD) both cause vasculitis of the medium-sized arteries, and share common features. They have overlapping clinical features. Treatment should be managed according to the severity of symptoms and persistence of clinical manifestations. Herein is described the case of a 14-year-old boy first diagnosed with KD, who then fulfilled the criteria for juvenile PAN due to the development of severe myalgia, persistent fever, polyneuropathy and coronary arterial dilatation. He also had acute toxoplasmosis at the onset of vasculitis symptoms. The final diagnosis was of juvenile PAN associated with toxoplasmosis infection. Toxoplasma infection can be considered as an etiological agent for PAN and other vasculitis syndromes. Awareness of toxoplasmosis-related PAN facilitates early diagnosis, and instigation of appropriate treatment. © 2014 The Authors. Pediatrics International © 2014 Japan Pediatric Society.

Mapping Mammalian Cell-type-specific Transcriptional Regulatory Networks Using KD-CAGE and ChIP-seq Data in the TC-YIK Cell Line

PubMed Central

Lizio, Marina; Ishizu, Yuri; Itoh, Masayoshi; Lassmann, Timo; Hasegawa, Akira; Kubosaki, Atsutaka; Severin, Jessica; Kawaji, Hideya; Nakamura, Yukio; Suzuki, Harukazu; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R. R.

2015-01-01

Mammals are composed of hundreds of different cell types with specialized functions. Each of these cellular phenotypes are controlled by different combinations of transcription factors. Using a human non islet cell insulinoma cell line (TC-YIK) which expresses insulin and the majority of known pancreatic beta cell specific genes as an example, we describe a general approach to identify key cell-type-specific transcription factors (TFs) and their direct and indirect targets. By ranking all human TFs by their level of enriched expression in TC-YIK relative to a broad collection of samples (FANTOM5), we confirmed known key regulators of pancreatic function and development. Systematic siRNA mediated perturbation of these TFs followed by qRT-PCR revealed their interconnections with NEUROD1 at the top of the regulation hierarchy and its depletion drastically reducing insulin levels. For 15 of the TF knock-downs (KD), we then used Cap Analysis of Gene Expression (CAGE) to identify thousands of their targets genome-wide (KD-CAGE). The data confirm NEUROD1 as a key positive regulator in the transcriptional regulatory network (TRN), and ISL1, and PROX1 as antagonists. As a complimentary approach we used ChIP-seq on four of these factors to identify NEUROD1, LMX1A, PAX6, and RFX6 binding sites in the human genome. Examining the overlap between genes perturbed in the KD-CAGE experiments and genes with a ChIP-seq peak within 50 kb of their promoter, we identified direct transcriptional targets of these TFs. Integration of KD-CAGE and ChIP-seq data shows that both NEUROD1 and LMX1A work as the main transcriptional activators. In the core TRN (i.e., TF-TF only), NEUROD1 directly transcriptionally activates the pancreatic TFs HSF4, INSM1, MLXIPL, MYT1, NKX6-3, ONECUT2, PAX4, PROX1, RFX6, ST18, DACH1, and SHOX2, while LMX1A directly transcriptionally activates DACH1, SHOX2, PAX6, and PDX1. Analysis of these complementary datasets suggests the need for caution in interpreting Ch

Immunoreactivity of polyclonal antibodies generated against the carboxy terminus of the predicted amino acid sequence of the Huntington disease gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alkatib, G.; Graham, R.; Pelmear-Telenius, A.

1994-09-01

A cDNA fragment spanning the 3{prime}-end of the Huntington disease gene (from 8052 to 9252) was cloned into a prokaryotic expression vector containing the E. Coli lac promoter and a portion of the coding sequence for {beta}-galactosidase. The truncated {beta}-galactosidase gene was cleaved with BamHl and fused in frame to the BamHl fragment of the Huntington disease gene 3{prime}-end. Expression analysis of proteins made in E. Coli revealed that 20-30% of the total cellular proteins was represented by the {beta}-galactosidase-huntingtin fusion protein. The identity of the Huntington disease protein amino acid sequences was confirmed by protein sequence analysis. Affinity chromatographymore » was used to purify large quantities of the fusion protein from bacterial cell lysates. Affinity-purified proteins were used to immunize New Zealand white rabbits for antibody production. The generated polyclonal antibodies were used to immunoprecipitate the Huntington disease gene product expressed in a neuroblastoma cell line. In this cell line the antibodies precipitated two protein bands of apparent gel migrations of 200 and 150 kd which together, correspond to the calculated molecular weight of the Huntington disease gene product (350 kd). Immunoblotting experiments revealed the presence of a large precursor protein in the range of 350-750 kd which is in agreement with the predicted molecular weight of the protein without post-translational modifications. These results indicate that the huntingtin protein is cleaved into two subunits in this neuroblastoma cell line and implicate that cleavage of a large precursor protein may contribute to its biological activity. Experiments are ongoing to determine the precursor-product relationship and to examine the synthesis of the huntingtin protein in freshly isolated rat brains, and to determine cellular and subcellular distribution of the gene product.« less

[Characteristics of cationic polymers PEI-CyD, PEI-PHPA, PEE-PHPA and PEI25kD in vitro and in vivo].

PubMed

Yao, Qi; Jin, Xue; Hu, Tian-nan; Wang, Qi-wen; Wang, Xun-shi; Hu, Qi-da; Xu, Sang; Zhou, Jun; Tang, Gu-ping

2012-11-01

To study the characteristics of cationic polymers polyethylenimine-β-cyclodextrin (PEI-CyD), polyethylenimine-poly-(3-hydroxypropyl)-aspartamide (PEI-PHPA), N,N-Dimethyldipropylenetriamine-Bis(3-aminopropyl)amine-aspartamide (PEE-PHPA) in vitro and in vivo. PEI-PHPA, PEI-CyD and PEE-PHPA were synthesized and the chemistry structure of PEI-PHPA, PEI-CyD and PEE-PHPA was confirmed by (1)H-NMR. The particle size and zeta potential of these polymers were measured, and capacity of plasmid DNA condensation was tested. The inhibition of COS-7, A549, HEK293 and C6 cells was measured by MTT assay. The transfection efficiency was determined in HEK293 cell lines. The toxicity, tissue distribution and transfection efficiency of cationic polymers were tested in vivo. When the N/P of polymers/DNA at 30, the particle sizes were close 250 nm and the zeta-potential were near 35 mv. They were able to condense DNA at N/P ratio < 5. The MTT assay showed that the IC(50) of PEE-PHPA was 21.5, 20.2, 7.30 and 37.1 μg/ml, and that of PEI25kD was 15.8, 18.3, 11.4 and 36.7 μg/ml in C6, COS-7, A549 and HEK293cell lines, respectively. The cell viability of PEI-CyD and PEI-PHPA in above cell lines was over 60%. They had high transfection efficiency in HEK293 cell lines. The LD(50) of PEI25Kd, PEI-CyD, PEI-PHPA and PEE-PHPA in vivo was 19.50, 100.4, 521.2 and 630.0, respectively by intraperitoneal (ip) injection. The contractions of these polymers were higher in kidney than in other organs and tissues.PEE-PHPA had slight effect on kidney and liver function. PEE and PEI25kD have higher transfection efficiency and higher toxicity; while PC and PHPA-PEI have lower toxicity and higher transfection efficiency to be used as non-viral gene vector.

A meshless method using radial basis functions for numerical solution of the two-dimensional KdV-Burgers equation

NASA Astrophysics Data System (ADS)

Zabihi, F.; Saffarian, M.

2016-07-01

The aim of this article is to obtain the numerical solution of the two-dimensional KdV-Burgers equation. We construct the solution by using a different approach, that is based on using collocation points. The solution is based on using the thin plate splines radial basis function, which builds an approximated solution with discretizing the time and the space to small steps. We use a predictor-corrector scheme to avoid solving the nonlinear system. The results of numerical experiments are compared with analytical solutions to confirm the accuracy and efficiency of the presented scheme.

Reassessment of carotid intima-media thickness by standard deviation score in children and adolescents after Kawasaki disease.

PubMed

Noto, Nobutaka; Kato, Masataka; Abe, Yuriko; Kamiyama, Hiroshi; Karasawa, Kensuke; Ayusawa, Mamoru; Takahashi, Shori

2015-01-01

Previous studies that used carotid ultrasound have been largely conflicting in regards to whether or not patients after Kawasaki disease (KD) have a greater carotid intima-media thickness (CIMT) than controls. To test the hypothesis that there are significant differences between the values of CIMT expressed as absolute values and standard deviation scores (SDS) in children and adolescents after KD and controls, we reviewed 12 published articles regarding CIMT on KD patients and controls. The mean ± SD of absolute CIMT (mm) in the KD patients and controls obtained from each article was transformed to SDS (CIMT-SDS) using age-specific reference values established by Jourdan et al. (J: n = 247) and our own data (N: n = 175), and the results among these 12 articles were compared between the two groups and the references for comparison of racial disparities. There were no significant differences in mean absolute CIMT and mean CIMT-SDS for J between KD patients and controls (0.46 ± 0.06 mm vs. 0.44 ± 0.04 mm, p = 0.133, and 1.80 ± 0.84 vs. 1.25 ± 0.12, p = 0.159, respectively). However, there were significant differences in mean CIMT-SDS for N between KD patients and controls (0.60 ± 0.71 vs. 0.01 ± 0.65, p = 0.042). When we assessed the nine articles on Asian subjects, the difference of CIMT-SDS between the two groups was invariably significant only for N (p = 0.015). Compared with the reference values, CIMT-SDS of controls was within the normal range at a rate of 41.6 % for J and 91.6 % for N. These results indicate that age- and race-specific reference values for CIMT are mandatory for performing accurate assessment of the vascular status in healthy children and adolescents, particularly in those after KD considered at increased long-term cardiovascular risk.

Hemodynamic Based Coronary Artery Aneurysm Thrombosis Risk Stratification in Kawasaki Disease Patients

NASA Astrophysics Data System (ADS)

Grande Gutierrez, Noelia; Mathew, M.; McCrindle, B.; Kahn, A.; Burns, J.; Marsden, A.

2017-11-01

Coronary artery aneurysms (CAA) as a result of Kawasaki Disease (KD) put patients at risk for thrombosis and myocardial infarction. Current AHA guidelines recommend CAA diameter >8 mm or Z-score >10 as the criterion for initiating systemic anticoagulation. Our hypothesis is that hemodynamic data derived from computational blood flow simulations is a better predictor of thrombosis than aneurysm diameter alone. Patient-specific coronary models were constructed from CMRI for a cohort of 10 KD patients (5 confirmed thrombosis cases) and simulations with fluid structure interaction were performed using the stabilized finite element Navier-Stokes solver available in SimVascular. We used a closed-loop lumped parameter network (LPN) to model the heart and vascular boundary conditions coupled numerically to the flow solver. An automated parameter estimation method was used to match LPN values to clinical data for each patient. Hemodynamic data analysis resulted in low correlation between Wall Shear Stress (WSS)/ Particle Residence Time (PRT) and CAA diameter but demonstrates the positive correlation between hemodynamics and adverse patient outcomes. Our results suggest that quantifying WSS and PRT should enable identification of regions at higher risk of thrombosis. We propose a quantitative method to non-invasively assess the abnormal flow in CAA following KD that could potentially improve clinical decision-making regarding anticoagulation therapy.

Immunohistochemical Evaluation of Leptin Expression in Wound Healing: A Clue to Exuberant Scar Formation.

PubMed

Seleit, Iman; Bakry, Ola A; Samaka, Rehab M; Tawfik, Amira S

2016-04-01

Leptin has been recognized as an important factor for promoting normal cutaneous wound healing. The aim of this work was to explore leptin expression in keloid and hypertrophic scars (HS) compared with surgical scars and normal skin. The relationship of this expression with clinicopathologic parameters of studied cases was also evaluated. Using immunohistochemical techniques, leptin was analyzed in skin biopsies of 60 nonobese subjects without metabolic syndrome who presented with keloids (20), HS (20), and surgical scars (20). Twenty normal skin samples, from age-matched, sex-matched, and body mass index-matched subjects, were enrolled as a control group. Leptin showed positive immunoreactivity in epidermis in all cases of surgical scars and keloids and in 75% of HS cases. Dermal expression in fibroblasts, inflammatory cells, and endothelial cells was positive in all cases of surgical scars and keloids and in 70% of HS cases. Leptin was overexpressed in keloids and HS compared with normal skin in epidermis (P<0.001 for both) and dermis (P<0.001 for both) and to surgical scars both in epidermis (P=0.0006, P=0.01, respectively) and dermis (P=0.0001, P=0.001, respectively). Higher leptin H score was significantly associated with older age (P=0.02) and positive family history (P=0.002) in keloid cases and with axial site in keloid and HS cases (P=0.001, P=0.02, respectively). Significant positive correlation was noted between epidermal and dermal leptin H scores in keloids (r=+0.37, P=0.04) and HS (r=+0.39, P=0.02). This may be due to epithelial-mesenchymal interactions in scar pathogenesis. In conclusion, in situ leptin overexpression may increase the possibility of keloid and HS occurrence through altered cytokine production and prolonged healing phases with excessive deposition and delayed collagen degradation. This may open an avenue for research for new therapeutic modalities based on its inhibition.

Evaluating a novel health system intervention for chronic kidney disease care using the RE-AIM framework: Insights after two years.

PubMed

Hynes, Denise M; Fischer, Michael J; Schiffer, Linda A; Gallardo, Rani; Chukwudozie, Ifeanyi Beverly; Porter, Anna; Berbaum, Michael; Earheart, Jennifer; Fitzgibbon, Marian L

2017-01-01

Using a quasi-experimental design, we implemented the Patient-Centered Medical Home for Kidney Disease (PCMH-KD), a comprehensive, multidisciplinary care team to improve quality of life and healthcare coordination for adult chronic hemodialysis (CHD) patients. This paper highlights our experience in the first two years of the study. We focus on the process dimensions of Reach, Adoption, and Implementation within the context of the RE-AIM framework. We established a new PCMH-KD model at two outpatient dialysis centers. During the intervention phase, adult patients were recruited for participation and data collection. We monitored RE-AIM measures to identify areas for potential adaptation of the care model. During the start-up phase, we engaged patients and stakeholders in planning the intervention, established the new PCMH-KD team, and trained new and continuing clinicians and staff at two dialysis centers. In the intervention phase we recruited 155 patients to participate. Patients had individual visits with the PCP (40%) and the CHWs (92%) (Reach). Patient feedback informed procedures for appointment scheduling (Adoption). The new PCMH-KD team members were consistent in their roles. With staff changes, some responsibilities were adapted for cross coverage (Implementation). After one year of start-up and one year of intervention, active monitoring of Reach, Implementation and Adoption measures have facilitated necessary adaptions in the planned intervention to accommodate scheduling demands and patient feedback in the PCMH-KD model. Insights from this trial may inform care of CHD patients more broadly. Copyright © 2016. Published by Elsevier Inc.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease.

PubMed

McNeal-Davidson, Ariane; Fournier, Anne; Spigelblatt, Linda; Saint-Cyr, Claire; Mir, Thomas S; Nir, Amiram; Dallaire, Frédéric; Cousineau, Jocelyne; Delvin, Edgard; Dahdah, Nagib

2012-10-01

The aim of the present study was to investigate the diagnostic value of the N-terminal B-type natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis. Basic biological tests and serum NT-proBNP levels obtained from acute KD patients were compared to that of febrile controls. NT-proBNP was considered abnormal based on the following definitions: above a cut-off determined on receiver operator characteristic (ROC) analysis, above the upper limit for age, or above 2 SD calculated from healthy children. Analyses were also performed for KD cases with complete or incomplete criteria combined and separately. There were 81 patients and 49 controls aged 3.60 ± 2.77 versus 4.25 ± 3.88 years (P= 0.69). ROC analysis yielded significant area under the curve for NT-proBNP. The sensitivity, specificity, positive and negative predictive values were 70.4-88.9%, 69.4-91.8%, 82.8-93.4%, and 65.2-79.1%. The odds ratios based on NT-proBNP definitions varied between 18.13 (95% confidence interval [CI]: 7.21-45.57), 20.82 (95%CI: 8.18-53.0), and 26.71 (95%CI: 8.64-82.57; P < 0.001). Results were reproducible for cases with complete or incomplete criteria separately. NT-proBNP is a reliable marker for the diagnosis of KD. Prospective clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

Cause-effect relations between 55 kD soluble TNF receptor concentrations and specific and unspecific symptoms in a patient with mild SLE disease activity: an exploratory time series analysis study.

PubMed

Schubert, Christian; Haberkorn, Julia; Ocaña-Peinado, Francisco M; König, Paul; Sepp, Norbert; Schnapka-Köpf, Mirjam; Fuchs, Dietmar

2015-09-21

This integrative single-case study investigated the 12 h-to-12 h cause-effect relations between 55 kD soluble tumor necrosis factor receptor type 1 (sTNF-R55) and specific and unspecific symptoms in a 52-year-old Caucasian woman with mild systemic lupus erythematosus (SLE) disease activity. The patient collected her entire urine for 56 days in 12 h-intervals to determine sTNF-R55/creatinine and protein/creatinine levels (ELISA, HPLC). Additionally, twice a day, she took notes on oral ulceration and facial rash; answered questionnaires (VAS) on fatigue, weakness, and joint pain; and measured body temperature orally. Time series analysis consisted of ARIMA modeling and cross-correlational analyses (significance level = p < 0.05). Time series analysis revealed both a circadian and a circasemiseptan rhythm in the urinary sTNF-R55 data. Moreover, several significant lagged correlations between urinary sTNF-R55 concentrations and SLE symptoms in both directions of effect were identified. Specifically, increased urinary sTNF-R55 concentrations preceded decreased urinary protein levels by 36-48 h (r = -0.213) and, in the opposite direction of effect, increased protein levels preceded increased sTNF-R55 concentrations by 24-36 h (r = +0.202). In addition, increased urinary sTNF-R55 levels preceded increased oral ulcers by 36-48 h (r = +0.277) and, conversely, increased oral ulceration preceded decreased sTNF-R55 levels by 36-48 h (r = -0.313). Moreover, increased urinary sTNF-R55 levels preceded decreased facial rash by 36-48 h (r = -0.223) and followed increased body temperature after 36-48 h (r = +0.209). Weakness, fatigue and joint pain were not significantly correlated with urinary sTNF-R55 levels. This study gathered first evidence of real-life, long-term feedback loops between cytokines and SLE symptoms in mild SLE disease activity. Such insights into the potential role of sTNF-R55 in SLE would not have been possible had we applied a pre-post design group study. These

Kawasaki disease: a rare pediatric pathology in Mexico. Twenty cases report from the Hospital Infantil del Estado de Sonora.

PubMed

Sotelo, Norberto; González, Luis Antonio

2007-01-01

Kawasaki disease (KD) is an etiological illness that is relatively unknown and scarcely identified in Mexico; it affects children mainly aged 1-4 years, evolves with fever, vasculitis in diverse organs, and in the heart the disease mainly affects the coronary arteries. Our aim was to inform the clinical findings and evolution of 20 patients diagnosed with KD. We reviewed the patient clinical files retrospectively and descriptively to obtain information with regard to age, sex, clinical signs, laboratory and consultory results, echocardiography findings, complications, evolution during hospitalization, followup, and out-patient ambulatory consultations. Eighteen patients were male, two were female, six developed coronary damage, two aortic mitral-valve insufficiency, one pericardial shedding, and one, myocarditis. All patients received gamma globulin treatment with aspirin, and 16 were controlled during 6-8 months after the acute medical profile. The opportune clinical diagnostic it is fundamental to establish an early treatment with gammmaglobuline to avoid injuries in the arterial coronary level. This injury may cause eventualy ischemia or myocardial infarct

[The detection of antibodies against HIV-1 24-kd protein. A clinico-serological correlation].

PubMed

Díaz Torres, H; Silva Cabrera, E; Rodríguez García, O; Bárcenas Moses, J; Lubián Caballero, A L

1996-01-01

The presence of antibodies against the HIV protein of 24 kd was studies by the parallel use of the DAVIH BLOT western blot and of the DAVIH AC P24 ELISA in serum samples from 176 patients at different HIV-1 infection stages. The results were correlated with the clinical classification of the patient at the moment of taking the sample and with the further evolution during 6 months. 57% of the patients with opportunistic minor infections and 96% of AIDS patients had low antibodies titres. Dead patients showed no reactivity or presented very low titres in samples taken before dying. Different titrations were observed in serum groups with an apparently uniform reactivity in the western blot. The results show and adequate clinical and serological correlation. Therefore, the DAVIH AC P24 ELISA could be useful in the clinical follow-up of HIV-1 infected persons.

Assessment Of Coronary Artery Aneurysms Using Transluminal Attenuation Gradient And Computational Modeling In Kawasaki Disease Patients

NASA Astrophysics Data System (ADS)

Grande Gutierrez, Noelia; Kahn, Andrew; Shirinsky, Olga; Gagarina, Nina; Lyskina, Galina; Fukazawa, Ryuji; Owaga, Shunichi; Burns, Jane; Marsden, Alison

2015-11-01

Kawasaki Disease (KD) can result in coronary artery aneurysms (CAA) in up to 25% of patients, putting them at risk of thrombus formation, myocardial infarction and sudden death. Clinical guidelines recommend CAA diameter >8 mm as the arbitrary criterion for initiating systemic anticoagulation. KD patient specific modeling and flow simulations suggest that hemodynamic data can predict regions at increased risk of thrombosis. Transluminal Attenuation Gradient (TAG) is determined from the change in radiological attenuation per vessel length and has been proposed as a non-invasive method for characterizing coronary stenosis from CT Angiography. We hypothesized that CAA abnormal flow could be quantified using TAG. We computed hemodynamics for patient specific coronary models using a stabilized finite element method, coupled numerically to a lumped parameter network to model the heart and vascular boundary conditions. TAG was quantified in the major coronary arteries. We compared TAG for aneurysmal and normal arteries and we analyzed TAG correlation with hemodynamic and geometrical parameters. Our results suggest that TAG may provide hemodynamic data not available from anatomy alone. TAG represents a possible extension to standard CTA that could help to better evaluate the risk of thrombus formation in KD.

Tachykinin NK2 receptor and functional mechanisms in human colon: changes with indomethacin and in diverticular disease and ulcerative colitis.

PubMed

Burcher, Elizabeth; Shang, Fei; Warner, Fiona J; Du, Qin; Lubowski, David Z; King, Denis W; Liu, Lu

2008-01-01

Neurokinin A (NKA) is an important spasmogen in human colon. We examined inflammatory disease-related changes in the tachykinin NK(2) receptor system in human sigmoid colon circular muscle, using functional, radioligand binding, and quantitative reverse transcription-polymerase chain reaction methods. In circular muscle strips, indomethacin enhanced contractile responses to NKA (p < 0.01) and to the NK(2) receptor-selective agonist [Lys(5),MeLeu(9),Nle(10)]-NKA(4-10) (p < 0.05) in both normal and acute diverticular disease (DD) specimens, indicating NK(2) receptor-mediated release of relaxant prostanoids. Contractile responses to both tachykinins were reduced in strips from DD (p < 0.001) and ulcerative colitis (UC) (p < 0.05) specimens. Responses to acetylcholine were no different in other strips from the same disease patients, demonstrating that the change in responsiveness to tachykinins in disease is specifically mediated by the NK(2) receptor. In membranes from UC specimens, receptor affinity for (125)I-NKA (median K(D) 0.91 nM, n = 16) was lower (p < 0.01) than that in age-matched control specimens (K(D) 0.55 nM, n = 40), whereas K(D) (0.65 nM, n = 28) in DD was no different from control. No disease-related changes in receptor number (B(max)) were found (mean, 2.0-2.5 fmol/mg of wet weight tissue), suggesting that the reduced contractile responses in disease are not due to a loss of receptor number. Different mechanisms may account for the reduced contractility in DD compared with UC. A gender-related difference in receptor density was seen in controls, with B(max) lower in females (1.77 fmol/mg, n = 15) than in males (2.60 fmol/mg, n = 25, p = 0.01). In contrast, no gender-related differences were seen in NK(2) receptor mRNA in control colonic muscle, indicating that the gender difference is a post-translational event.

Infliximab for the Treatment of Refractory Kawasaki Disease: A Nationwide Survey in Japan.

PubMed

Masuda, Hiroshi; Kobayashi, Tohru; Hachiya, Akira; Nakashima, Yasutaka; Shimizu, Hiroyuki; Nozawa, Tomo; Ogihara, Yoshihito; Ito, Shuichi; Takatsuki, Shinichi; Katsumata, Nobuyuki; Suzuki, Yasuo; Takenaka, Satoshi; Hirono, Keiichi; Kobayashi, Tomio; Suzuki, Hiroshi; Suganuma, Eisuke; Takahashi, Kei; Saji, Tsutomu

2018-04-01

To assess the safety and efficacy of infliximab (IFX) for the treatment of patients with Kawasaki disease (KD). This was a nationwide survey of 274 Japanese institutions exploring how IFX was used to treat patients with KD. The patients' sex, age, treatment course, pre- and post-IFX therapy blood test results, coronary artery lesions (CALs), and adverse events (AEs) were evaluated. We analyzed 434 patients with KD who received IFX between March 2005 and November 2014. The median age at onset was 33 months (range 1-138), and 66 patients (15.2%) were under 1 year old. In all cases, IFX was administered as additional treatment. The median days of illness at the initiation of IFX was 9 days. In 275 patients (63.4%), IFX was administered as third-line treatment, and in 106 patients (24.4%), IFX was administered as fourth-line treatment. Single dose IFX 5 mg/kg was administered to 412 patients (94.9%). After IFX, 363 patients (83.6%) became afebrile within 2 days, and the white blood cell count, percentage of neutrophils, and serum C-reactive protein levels significantly decreased (P < .001), although 119 patients (27.4%) received additional treatment. Before IFX, 132 patients (30.4%) had already developed CALs. In patients without CALs before IFX, 31 patients (10.3%) newly developed CAL after IFX, whereas 32 patients (24.2%) with CAL before IFX showed increased CAL severity. Eighty AEs were observed in 69 patients (15.9%); however, serious AEs were few and reversible. IFX might be an effective and tolerable treatment for refractory KD. Copyright © 2017 Elsevier Inc. All rights reserved.

NdYag Laser for Acne Keloidalis Nuchae

ClinicalTrials.gov

2013-03-27

Acne Keloidalis Nuchae; NdYag Laser; AKN; Acne Keloidalis; AK; Dermatitis Papillaris Capillitii; Folliculitis Keloidalis Nuchae; Sycosis Nuchae; Acne Keloid; Keloidal Folliculitis; Lichen Keloidalis Nuchae; Folliculitis Nuchae Scleroticans; Sycosis Framboesiformis

A 3-month-old infant with atypical Kawasaki disease.

PubMed

Lertamornkitti, Nichkamol; Wangjirapan, Anchalee

2018-05-30

We report a 3-month-old girl who presented with high-grade fever for 3 days. Her initial physical examination was normal. Investigation showed abnormal white cells in her urine. She was diagnosed with a urinary tract infection and received an antibiotic for 1 day. After that, she developed a generalised maculopapular rash over her body. An adverse drug reaction from the antibiotic was suspected, and the patient was referred to our hospital. On admission, she still had fever and was irritable. She was diagnosed with sepsis and given another broad-spectrum antibiotic for 2 days. However, her fever still persisted. An additional thorough physical examination showed redness of her BCG inoculation scar. Consequently, a diagnosis of Kawasaki disease (KD) was made. After she received intravenous immunoglobulin, her fever diminished straight away. This case highlights an unusual manifestation of KD in an uncommonly young age group. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

How Can a Ketogenic Diet Improve Motor Function?

PubMed Central

Veyrat-Durebex, Charlotte; Reynier, Pascal; Procaccio, Vincent; Hergesheimer, Rudolf; Corcia, Philippe; Andres, Christian R.; Blasco, Hélène

2018-01-01

A ketogenic diet (KD) is a normocaloric diet composed by high fat (80–90%), low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs) production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production. KD is a therapy that has been used for almost a century to treat medically intractable epilepsy and has been increasingly explored in a number of neurological diseases. Motor function has also been shown to be improved by KD and/or medium-chain triglyceride diets in rodent models of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinal cord injury. These studies have proposed that KD may induce a modification in synaptic morphology and function, involving ionic channels, glutamatergic transmission, or synaptic vesicular cycling machinery. However, little is understood about the molecular mechanisms underlying the impact of KD on motor function and the perspectives of its use to acquire the neuromuscular effects. The aim of this review is to explore the conditions through which KD might improve motor function. First, we will describe the main consequences of KD exposure in tissues involved in motor function. Second, we will report and discuss the relevance of KD in pre-clinical and clinical trials in the major diseases presenting motor dysfunction. PMID:29434537

Correlative Light and Electron Microscopy (CLEM) and its applications in infectious disease

DTIC Science & Technology

2016-05-20

Martin, Molecular trapping of a fluorescent ceramide analogue at the Golgi apparatus of fixed cells: interaction with endogenous lipids provides a...diagnostic tool for functionally related structural biological studies. CLEM is particularly useful in infectious disease research where there is need to...25KD, there are critiques and concerns that the size of the tag and oligomers formation may affect the function of the target protein and introduce

Summary of Notifiable Diseases, United States, 1995. Volume 44/No. 53

DTIC Science & Technology

1996-10-25

Tetanus Toxic-shock syndrome Trichinosis Tuberculosis Typhoid fever Yellow f eve r+ *Although varicella is not a nationally notifiable disease, the...KD, Gerber AR, et al. Shigella dysenterlaetype 1 infections in U.S. travelers to Mexico . Lancet 1989:543-5. Ries AA, Wells JG, Olivola D, et al...Woodruff BA, Pavia AT, Blake PA. A new look at typhoid vaccination: information for the practic- ing physician. JAMA 1991;265:756-9. varicella CDC

Validation of the Andon KD-5965 upper-arm blood pressure monitor for home blood pressure monitoring according to the European Society of Hypertension International Protocol revision 2010.

PubMed

Huang, Jinhua; Li, Zhijie; Li, Guimei; Liu, Zhaoying

2015-10-01

This study aimed to evaluate the accuracy of the Andon KD-5965 upper-arm blood pressure monitor according to the European Society of Hypertension International Protocol revision 2010. Systolic and diastolic blood pressures were sequentially measured in 33 adults, with 20 women using a mercury sphygmomanometer (two observers) and the Andon KD-5965 device (one supervisor). A total of 99 pairs of comparisons were obtained from 33 participants for judgments in two parts with three grading phases. The device achieved the targets in part 1 of the validation study. The number of absolute differences between the device and observers within 5, 10, and 15 mmHg was 70/99, 91/99, and 98/99, respectively, for systolic blood pressure and 81/99, 99/99, and 99/99, respectively, for diastolic blood pressure. The device also fulfilled the criteria in part 2 of the validation study. Twenty-five and 29 participants, for systolic and diastolic blood pressure, respectively, had at least two of the three device-observers differences within 5 mmHg (required≥24). Two and one participants for systolic and diastolic blood pressure, respectively, had all three device-observers comparisons greater than 5 mmHg. According to the validation results, with better performance for diastolic blood pressure than that for systolic blood pressure, the Andon automated oscillometric upper-arm blood pressure monitor KD-5965 fulfilled the requirements of the European Society of Hypertension International Protocol revision 2010, and hence can be recommended for blood pressure measurement in adults.

Thrombospondin-2 predicts response to treatment with intravenous immunoglobulin in children with Kawasaki disease.

PubMed

Yang, Shuai; Song, Ruixia; Li, Xiaohui; Zhang, Ting; Fu, Jin; Cui, Xiaodai

2018-01-01

To investigate the predictive value of thrombospondin-2 (TSP-2) in assessing the response to intravenous immunoglobulin (IVIG) in children with acute Kawasaki disease (KD). This was a cohort study with controls. 71 children with KD were recruited as the case group, including IVIG non-responder (n=17) and IVIG responder (n=54), and healthy children (n=27) and febrile children (n=30) were used as control groups. ELISA was used to measure plasma TSP-2 and TSP-1 levels. The rank-sum test was used to compare groups of non-normally distributed data. Predictive value was evaluated through the receiver operating characteristic (ROC) curve. Compared with the control groups, the plasma TSP-2 levels in acute KD were significantly elevated (TSP-2: 31.00 (24.02, 39.28) vs 21.93 (17.00, 24.73) vs 16.23 (14.00, 19.64) ng/mL, P<0.001). The plasma TSP-2 level in the IVIG non-responder was significantly higher than the responder group (37.58 (31.86, 43.98) vs 27.84 (21.88, 33.48) ng/mL, P=0.002). When using an ROC curve to analyse the predictive effect of TSP-2 on non-responsiveness to IVIG treatment, the area under the curve was 0.752 (0.630, 0.875) (P=0.002). When the cut-off value for TSP-2 was 31.50 ng/mL, the sensitivity was 82.35%, the specificity was 64.81%. The plasma TSP-2 level was elevated in acute KD and it might be a novel predictor for IVIG resistance, which could help guide clinicians to choose individualised initial therapeutic regimens.

Adhesion inhibition of Mycoplasma iowae to chicken lymphoma DT40 cells by monoclonal antibodies reacting with a 65-kD polypeptide.

PubMed

Fiorentin, L; Panangala, V S; Zhang, Y; Toivio-Kinnucan, M

1998-01-01

Tissue- and cell-specific attachment of mycoplasmas is a key aspect of the host-parasite relationship. In this study, monoclonal antibodies (MAbs) recognizing surface membrane polypeptides with molecular masses of 46 kD (p46) and 65 kD (p65), respectively, were examined in a microtiter cell attachment (agglutination) inhibition assay. MAbs MI3, MI6, and MI12 reacting with p65 polypeptide of Mycoplasma iowae inhibited attachment of the organisms to chicken lymphoma (DT 40) cells. One MAb (MI2) that reacted with p65 in immunoblots did not inhibit cell attachment, possibly because of the intrinsic native conformation of the epitope(s) in intact mycoplasmas as opposed to the linear state (sodium dodecyl sulfate denatured) in immunoblots. More pronounced M. iowae adherence inhibition was demonstrated by polyclonal turkey and mouse anti-M. iowae antisera compared with MAbs. Immunogold labelling followed by electron microscopy allowed us to localize the MAb-recognized epitopes on the membrane surface of M. iowae. On the basis of the cell attachment inhibition of M. iowae by specific MAbs (MI3, MI6, and MI12), we propose that the p65 polypeptide plays a role in cytadherence. The ability of polyclonal antisera to inhibit attachment of M. iowae more efficiently than the MAbs suggests that additional epitopes within p65 and/or other proteins are involved in cell attachment.

A comparison of efficacy of six prediction models for intravenous immunoglobulin resistance in Kawasaki disease.

PubMed

Qian, Weiguo; Tang, Yunjia; Yan, Wenhua; Sun, Ling; Lv, Haitao

2018-03-09

Kawasaki disease (KD) is the most common pediatric vasculitis. Several models have been established to predict intravenous immunoglobulin (IVIG) resistance. The present study was aimed to evaluate the efficacy of prediction models using the medical data of KD patients. We collected the medical records of patients hospitalized in the Department of Cardiology in Children's Hospital of Soochow University with a diagnosis of KD from Jan 2015 to Dec 2016. IVIG resistance was defined as recrudescent or persistent fever ≥36 h after the end of their IVIG infusion. Patients with IVIG resistance tended to be younger, have higher occurrence of rash and changes of extremities. They had higher levels of c-reactive protein, aspartate aminotransferase, neutrophils proportion (N%), total bilirubin and lower level of albumin. Our prediction model had a sensitivity of 0.72 and a specificity of 0.75. Sensitivity of Kobayashi, Egami, Kawamura, Sano and Formosa were 0.72, 0.44, 0.48, 0.20, and 0.68, respectively. Specificity of these models were 0.62, 0.82, 0.66, 0.91, and 0.48, respectively. Our prediction model had a powerful predictive value in this area, followed by Kobayashi model while all the other prediction models had less excellent performances than ours.

Validation of the Andon KD-5851 upper arm blood pressure monitor, for self-measurement according to the European Society of Hypertension International Protocol revision 2010.

PubMed

Wu, Lili; Jiao, Yinghui; Wang, Chengdong; Chen, Lei; Di, Dalin; Zhang, Haiyan

2015-08-01

This study aimed to validate the Andon KD-5851 upper arm blood pressure (BP) monitor according to the European Society of Hypertension International Protocol (ESH-IP) revision 2010. A total of 33 eligible participants were included in the study. Sequential measurements of BPs were performed using a mercury sphygmomanometer and the device, and the data analysis was carried out following precisely the ESH-IP revision 2010. The device had 82, 98, and 99 measurements within 5, 10, and 15 mmHg for systolic blood pressure and 85, 95, and 99 measurements for diastolic blood pressure, respectively. The average device-observer difference was -0.53±4.00 mmHg for systolic blood pressure and -1.15±4.06 mmHg for diastolic blood pressure. The device passed all the criteria according to the ESH-IP revision 2010. According to the validation results on the basis of the ESH-IP revision 2010, the Andon KD-5851 upper arm BP monitor can be recommended for self/home measurement in adults. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Korteweg-deVries-Burgers (KdVB) equation in a five component cometary plasma with kappa described electrons and ions

NASA Astrophysics Data System (ADS)

Michael, Manesh; Willington, Neethu T.; Jayakumar, Neethu; Sebastian, Sijo; Sreekala, G.; Venugopal, Chandu

2016-12-01

We investigate the existence of ion-acoustic shock waves in a five component cometary plasma consisting of positively and negatively charged oxygen ions, kappa described hydrogen ions, hot solar electrons, and slightly colder cometary electrons. The KdVB equation has been derived for the system, and its solution plotted for different kappa values, oxygen ion densities, as well as the temperature ratios for the ions. It is found that the amplitude of the shock wave decreases with increasing kappa values. The strength of the shock profile decreases with increasing temperatures of the positively charged oxygen ions and densities of negatively charged oxygen ions.

Numerical solution of the generalized, dissipative KdV-RLW-Rosenau equation with a compact method

NASA Astrophysics Data System (ADS)

Apolinar-Fernández, Alejandro; Ramos, J. I.

2018-07-01

The nonlinear dynamics of the one-dimensional, generalized Korteweg-de Vries-regularized-long wave-Rosenau (KdV-RLW-Rosenau) equation with second- and fourth-order dissipative terms subject to initial Gaussian conditions is analyzed numerically by means of three-point, fourth-order accurate, compact finite differences for the discretization of the spatial derivatives and a trapezoidal method for time integration. By means of a Fourier analysis and global integration techniques, it is shown that the signs of both the fourth-order dissipative and the mixed fifth-order derivative terms must be negative. It is also shown that an increase of either the linear drift or the nonlinear convection coefficients results in an increase of the steepness, amplitude and speed of the right-propagating wave, whereas the speed and amplitude of the wave decrease as the power of the nonlinearity is increased, if the amplitude of the initial Gaussian condition is equal to or less than one. It is also shown that the wave amplitude and speed decrease and the curvature of the wave's trajectory increases as the coefficients of the second- and fourth-order dissipative terms are increased, while an increase of the RLW coefficient was found to decrease both the damping and the phase velocity, and generate oscillations behind the wave. For some values of the coefficients of both the fourth-order dissipative and the Rosenau terms, it has been found that localized dispersion shock waves may form in the leading part of the right-propagating wave, and that the formation of a train of solitary waves that result from the breakup of the initial Gaussian conditions only occurs in the absence of both Rosenau's, Kortweg-de Vries's and second- and fourth-order dissipative terms, and for some values of the amplitude and width of the initial condition and the RLW coefficient. It is also shown that negative values of the KdV term result in steeper, larger amplitude and faster waves and a train of

Results of a prospective clinical study on the diagnostic performance of standard magnetic resonance imaging in comparison to a combination of 3T MRI and additional CT imaging in Kienböck's disease.

PubMed

Stahl, Stephane; Hentschel, Pascal; Ketelsen, Dominik; Grosse, Ulrich; Held, Manuel; Wahler, Theodora; Syha, Roland; Schaller, Hans-Eberhard; Nikolaou, Konstantin; Grözinger, Gerd

2017-05-01

This prospective clinical study examined standard wrist magnetic resonance imaging (MRI) examinations and the incremental value of computed tomography (CT) in the diagnosis of Kienböck's disease (KD) with regard to reliability and precision in the different diagnostic steps during diagnostic work-up. Sixty-four consecutive patients referred between January 2009 and January 2014 with positive initial suspicion of KD according to external standard wrist MRI were prospectively included (step one). Institutional review board approval was obtained. Clinical examination by two handsurgeons were followed by wrist radiographs (step two), ultrathin-section CT, and 3T contrast-enhanced MRI (step three). Final diagnosis was established in a consensus conference involving all examiners and all examinations results available from step three. In 12/64 patients, initial suspicion was discarded at step two and in 34/64 patients, the initial suspicion of KD was finally discarded at step three. The final external MRI positive predictive value was 47%. The most common differential diagnoses at step three were intraosseous cysts (n=15), lunate pseudarthrosis (n=13), and ulnar impaction syndrome (n=5). A correlation between radiograph-based diagnoses (step two) with final diagnosis (step three) showed that initial suspicion of stage I KD had the lowest sensitivity for correct diagnosis (2/11). Technical factors associated with a false positive external MRI KD diagnosis were not found. Standard wrist MRI should be complemented with thin-section CT, and interdisciplinary interpretation of images and clinical data, to increase diagnostic accuracy in patients with suspected KD. Copyright © 2017. Published by Elsevier B.V.

Axillary, Oral and Rectal Routes of Temperature Measurement During Treatment of Acute Kawasaki Disease.

PubMed

Kanegaye, John T; Jones, Jefferson M; Burns, Jane C; Jain, Sonia; Sun, Xiaoying; Jimenez-Fernandez, Susan; Berry, Erika; Pancheri, Joan M; Jaggi, Preeti; Ramilo, Octavio; Tremoulet, Adriana H

2016-01-01

Important therapeutic decisions are made based on the presence or absence of fever in patients with Kawasaki disease (KD), yet no standard method or threshold exists for temperature measurement during the diagnosis and treatment of these patients. We sought to compare surface and internal (rectal or oral) routes of temperature measurement for the detection of fever as a marker of treatment resistance. From a randomized, placebo-controlled trial of infliximab as an adjunct to primary intravenous immunoglobulin treatment for acute KD, we collected concurrent (within 5 minutes) axillary and internal temperature measurements and performed receiver-operating characteristic and Bland-Altman analyses. We also determined the ability of surface temperatures to detect treatment resistance defined by internal temperature measurements. Among 452 oral-axillary and 439 rectal-axillary pairs from 159 patients, mean axillary temperatures were 0.25 and 0.43 °C lower than oral and rectal temperatures and had high receiver-operating characteristic areas under curves. However, axillary temperatures ≥ 38.0 °C had limited sensitivity to detect fever defined by internal temperatures. Axillary thresholds of 37.5 and 37.2 °C provided maximal sensitivity and specificity to detect oral and rectal temperatures ≥ 38.0 °C, respectively. Axillary temperatures are an insensitive metric for fevers defining treatment resistance. Clinical trials should adopt temperature measurement by the oral or rectal routes for adjudication of treatment resistance in KD.

Coronary artery lesions and the increasing incidence of Kawasaki disease resistant to initial immunoglobulin.

PubMed

Kibata, Tetsuhiro; Suzuki, Yasuo; Hasegawa, Shunji; Matsushige, Takeshi; Kusuda, Takeshi; Hoshide, Madoka; Takahashi, Kazumasa; Okada, Seigo; Wakiguchi, Hiroyuki; Moriwake, Tadashi; Uchida, Masashi; Ohbuchi, Noriko; Iwai, Takashi; Hasegawa, Masanari; Ichihara, Kiyoshi; Yashiro, Mayumi; Makino, Nobuko; Nakamura, Yosikazu; Ohga, Shouichi

2016-07-01

Kawasaki disease (KD) is a systemic vasculitis of childhood involving coronary arteries. Treatment for intractable cases at a higher risk of cardiac sequelae remains controversial. Clinical outcomes of KD patients diagnosed in Yamaguchi prefecture, Japan between 2003 and 2014 were analyzed using the medical records from all 14 hospitals covering the prefecture. The study included 1487 patients (male:female, 873:614; median age at diagnosis, 24months). The proportion of initial intravenous immunoglobulin (IVIG)-resistant patients increased from 7% to 23% during this decade, although no patients died. Twenty-four patients developed coronary artery lesions (CALs) over one month after the KD onset. The incidence of CAL in patients who received corticosteroid during the disease course (10/37; 27.0%) was higher than that in those who did not (14/1450; 0.97%, p=2.0×10(-35)). Nine patients who responded to initial IVIG plus corticosteroids had no CAL. Conversely, IVIG-resistant patients with alternate corticosteroid therapy more frequently developed CAL than those without it (10/28; 35.7% vs. 5/194; 2.6%, p=8.9×10(-10)). Multivariate analyses indicated corticosteroid therapy (p<0.0001), hyperbilirubinemia (p=0.0010), and a longer number of days before treatment (p=0.0005) as risk factors associated with CAL over a month after onset. The odds ratio of corticosteroid use increased from 18.3 to 43.5 if the cases were limited to initial IVIG non-responders and corticosteroid free-IVIG responders. IVIG-failure has recently increased. The incidence of CAL increased in intractable cases with prolonged corticosteroid use. Corticosteroid may not be alternate choice for IVIG-failure to reduce the risk of cardiac sequelae. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus induces anti-fibrotic effect via inhibition of Wnt and TGF-β signaling.

PubMed

Lee, Won Jai; Lee, Jung-Sun; Ahn, Hyo Min; Na, Youjin; Yang, Chae Eun; Lee, Ju Hee; Hong, JinWoo; Yun, Chae-Ok

2017-11-08

Aberrant activation of the canonical Wingless type (Wnt) signaling pathway plays a key role in the development of hypertrophic scars and keloids, and this aberrant activation of Wnt pathway can be a potential target for the development of novel anti-fibrotic agents. In this study, we evaluated the anti-fibrotic potential of a soluble Wnt decoy receptor (sLRP6E1E2)-expressing non-replicating adenovirus (Ad; dE1-k35/sLRP6E1E2) on human dermal fibroblasts (HDFs), keloid fibroblasts (KFs), and keloid tissue explants. Higher Wnt3a and β-catenin expression was observed in the keloid region compared to the adjacent normal tissues. The activity of β-catenin and mRNA expression of type-I and -III collagen were significantly decreased following treatment with dE1-k35/sLRP6E1E2 in HDFs and KFs. The expression of LRP6, β-catenin, phosphorylated glycogen synthase kinase 3 beta, Smad 2/3 complex, and TGF-β1 were decreased in Wnt3a- or TGF-β1-activated HDFs, following administration of dE1-k35/sLRP6E1E2. Moreover, dE1-k35/sLRP6E1E2 markedly inhibited nuclear translocation of both β-catenin and Smad 2/3 complex. The expression levels of type-I and -III collagen, fibronectin, and elastin were also significantly reduced in keloid tissue explants after treatment with dE1-k35/sLRP6E1E2. These results indicate that Wnt decoy receptor-expressing Ad can degrade extracellular matrix in HDFs, KFs, and primary keloid tissue explants, and thus it may be beneficial for treatment of keloids.

Ketogenic diets, mitochondria, and neurological diseases

PubMed Central

Gano, Lindsey B.; Patel, Manisha; Rho, Jong M.

2014-01-01

The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate “classic KD”, as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD. PMID:24847102

[Changes in peripheral blood T helper 9 cells and interleukin-9 in children in the acute stage of Kawasaki disease].

PubMed

Sun, Rui-Li; Zhu, Shu-Xia; Zhang, Yan-Yan; Wu, Yi-Fei; Wang, Xing-Jian

2016-08-01

To investigate the changes in the expression levels of peripheral blood T helper 9 (Th9) cells and cytokine interleukin-9 (IL-9) in children in the acute stage of Kawasaki disease (KD) and their clinical significance. A total of 45 children in the acute stage of KD who were treated from April 2014 to July 2015 were enrolled, and the children were followed up in the recovery stage. Another 45 healthy children who underwent physical examination were enrolled as the control group. Flow cytometry was used to measure the percentage of peripheral blood Th9 cells, and ELISA was used to measure the serum level of IL-9. The children in the acute stage of KD showed a significantly higher percentage of Th9 cells and a significantly higher serum level of IL-9 compared with those in the recovery stage and the control group (P<0.05). The percentage of Th9 cells and serum level of IL-9 showed no significant differences between the children in the recovery stage and those in the control group (P>0.05). In the acute stage, the percentage of Th9 cells was positively correlated with the levels of IL-9, C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), platelet count (PLT), and globulin (r=0.624, 0.324, 0.402, 0.382, 0.467, and 0.386 respectively, all P<0.05), but negatively correlated with serum albumin (r=-0.306, P<0.05). The serum level of IL-9 was positively correlated with the levels of CRP, PCT, ESR, PLT, and globulin (r=0.365, 0.456, 0.403, 0.423, and 0.453 respectively, all P<0.05), but negatively correlated with serum albumin (r=-0.343, P<0.05). The children in the acute stage of KD show significant increases in the percentage of peripheral Th9 cells and serum cytokine IL-9 level, which return to normal in the recovery stage. In the acute stage of KD, the expression levels of Th9 and IL-9 are closely correlated with laboratory markers. The results suggest that Th9 cells and IL-9 play important roles in the pathogenesis and outcome of KD.

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1985 Annual Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaattari, Stephen L.

1986-06-01

Bacterial kidney disease (BRD) has been and remains a chronic contributory problem limiting the productivity of salmon in the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon to Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem, and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability tomore » activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's second year was to chemically modify the major antigens of Renibacteirium salmoninarum, immunize coho salmon (Oncorhynchus kisutch), and to test the immunogenicity of the preparations used. Immunogenicity of the antigenic material was tested by (1) admixture experiments, using whole KD cells with muramyl dipepetide, Vibrio anguillarum extract, E. coli lipopolysaccharide, or Mycobacterium tuberculosis in Freund's complete adjuvant. In addition to these goals a number of important techniques have been developed in order to facilitate the production of the vaccine. These procedures include: (1) the use of the soluble antigen for diagnosis in the ELISA and Western blot analysis, (2) detection of salmonid anti-KD antibodies by an ELISA technique, (3) detection of cellular immune responses to the soluble antigen, and (4) development of immersion challenge procedures for bacterial kidney disease (BKD).« less

Atypical desquamation in a 2.5-year-old boy with Kawasaki disease: A case report.

PubMed

Adib, Ali; Fazel, Ali; Nabavizadeh, Seyed Hesamedin; Alyasin, Sohaila; Kashef, Sara

2017-02-01

Kawasaki disease (KD) is a vasculitis that mostly affects children under 5 years of age. This article presents a 2.5-year-old boy who presented with 6 days of fever, generalized maculopapular rash, bilateral non-exudative conjunctivitis, cracked lips, right cervical lymphadenopathy, erythematous extremities, and perianal desquamation. Laboratory studies showed leukocytosis and sterile pyuria. Because diagnosis of KD was proved, oral acetylsalicylic acid with the anti-inflammatory dose and intravenous immunoglobulin were started for him. On the seventh day of admission time, he developed desquamation and erythema on the site of his right cervical lymphadenopathy as well as periungual scaling. About three weeks after starting the treatment, scaling of the cervical lymphadenopathy and periungual area stopped. Echocardiography was performed for him three times: at the time of diagnosis, four weeks, and 6 months later and revealed normal coronary arteries. We report this sign, desquamation on the site of cervical lymphadenopathy, as a new finding.

The cytokine-protease connection: identification of a 96-kD THP-1 gelatinase and regulation by interleukin-1 and cytokine inducers.

PubMed

Van Ranst, M; Norga, K; Masure, S; Proost, P; Vandekerckhove, F; Auwerx, J; Van Damme, J; Opdenakker, G

1991-05-01

The induction of proteolytic enzymes is an important mechanism in the migration of monocytes into tissues and body fluids. The monocytic cell line THP-1 was used as a model system to study the production of a particular gelatinase. Upon stimulation with phorbol myristate acetate (PMA) the cells differentiated to the adherent phenotype and produced significant amounts of a 96-kD gelatinase in a dose-dependent way. The secretion rate was maximal between 12 and 24 h after induction. Study of gelatinase mRNA steady state levels showed that the synthesis of THP-1 gelatinase is regulated by PMA at transcriptional or posttranscriptional levels. Stimulation of signal transduction pathways with other substances, including calcium ionophore A 23187, dibutyryl cyclic AMP, and dexamethasone, were ineffective in inducing gelatinase mRNA or enzyme activity. However, THP-1 cells were responsive to the cytokine interleukin (IL)-1 beta, to bacterial lipopolysaccharide (LPS), and the lectin concanavalin A (Con A), the kinetics of gelatinase induction being similar to those of induction by PMA. The THP-1 cells did not synthesize and/or secrete detectable levels of IL-6 after stimulation with PMA, Con A, LPS, or IL-1 beta. The 96-kD monocytic THP-1 gelatinase was shown to be a neutral metalloproteinase that cross-reacted with hepatoma-derived and neutrophil gelatinases in immunoprecipitation experiments. The active enzyme produced by THP-1 cells consistently showed, however, a molecular mass different from that of normal granulocyte-, monocyte-, and tumor cell-derived gelatinases.(ABSTRACT TRUNCATED AT 250 WORDS)

Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in neurofibromatosis type I (NF1) disease model cells.

PubMed

Hirayama, Mio; Kobayashi, Daiki; Mizuguchi, Souhei; Morikawa, Takashi; Nagayama, Megumi; Midorikawa, Uichi; Wilson, Masayo M; Nambu, Akiko N; Yoshizawa, Akiyasu C; Kawano, Shin; Araki, Norie

2013-05-01

Neurofibromatosis type 1 (NF1) tumor suppressor gene product, neurofibromin, functions in part as a Ras-GAP, and though its loss is implicated in the neuronal abnormality of NF1 patients, its precise cellular function remains unclear. To study the molecular mechanism of NF1 pathogenesis, we prepared NF1 gene knockdown (KD) PC12 cells, as a NF1 disease model, and analyzed their molecular (gene and protein) expression profiles with a unique integrated proteomics approach, comprising iTRAQ, 2D-DIGE, and DNA microarrays, using an integrated protein and gene expression analysis chart (iPEACH). In NF1-KD PC12 cells showing abnormal neuronal differentiation after NGF treatment, of 3198 molecules quantitatively identified and listed in iPEACH, 97 molecules continuously up- or down-regulated over time were extracted. Pathway and network analysis further revealed overrepresentation of calcium signaling and transcriptional regulation by glucocorticoid receptor (GR) in the up-regulated protein set, whereas nerve system development was overrepresented in the down-regulated protein set. The novel up-regulated network we discovered, "dynein IC2-GR-COX-1 signaling," was then examined in NF1-KD cells. Validation studies confirmed that NF1 knockdown induces altered splicing and phosphorylation patterns of dynein IC2 isomers, up-regulation and accumulation of nuclear GR, and increased COX-1 expression in NGF-treated cells. Moreover, the neurite retraction phenotype observed in NF1-KD cells was significantly recovered by knockdown of the dynein IC2-C isoform and COX-1. In addition, dynein IC2 siRNA significantly inhibited nuclear translocation and accumulation of GR and up-regulation of COX-1 expression. These results suggest that dynein IC2 up-regulates GR nuclear translocation and accumulation, and subsequently causes increased COX-1 expression, in this NF1 disease model. Our integrated proteomics strategy, which combines multiple approaches, demonstrates that NF1-related neural

Cross-sectional analysis of BioBank Japan clinical data: A large cohort of 200,000 patients with 47 common diseases.

PubMed

Hirata, Makoto; Kamatani, Yoichiro; Nagai, Akiko; Kiyohara, Yutaka; Ninomiya, Toshiharu; Tamakoshi, Akiko; Yamagata, Zentaro; Kubo, Michiaki; Muto, Kaori; Mushiroda, Taisei; Murakami, Yoshinori; Yuji, Koichiro; Furukawa, Yoichi; Zembutsu, Hitoshi; Tanaka, Toshihiro; Ohnishi, Yozo; Nakamura, Yusuke; Matsuda, Koichi

2017-03-01

To implement personalized medicine, we established a large-scale patient cohort, BioBank Japan, in 2003. BioBank Japan contains DNA, serum, and clinical information derived from approximately 200,000 patients with 47 diseases. Serum and clinical information were collected annually until 2012. We analyzed clinical information of participants at enrollment, including age, sex, body mass index, hypertension, and smoking and drinking status, across 47 diseases, and compared the results with the Japanese database on Patient Survey and National Health and Nutrition Survey. We conducted multivariate logistic regression analysis, adjusting for sex and age, to assess the association between family history and disease development. Distribution of age at enrollment reflected the typical age of disease onset. Analysis of the clinical information revealed strong associations between smoking and chronic obstructive pulmonary disease, drinking and esophageal cancer, high body mass index and metabolic disease, and hypertension and cardiovascular disease. Logistic regression analysis showed that individuals with a family history of keloid exhibited a higher odds ratio than those without a family history, highlighting the strong impact of host genetic factor(s) on disease onset. Cross-sectional analysis of the clinical information of participants at enrollment revealed characteristics of the present cohort. Analysis of family history revealed the impact of host genetic factors on each disease. BioBank Japan, by publicly distributing DNA, serum, and clinical information, could be a fundamental infrastructure for the implementation of personalized medicine. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

A distinct X-linked syndrome involving joint contractures, keloids, large optic cup-to-disc ratio, and renal stones results from a filamin A (FLNA) mutation.

PubMed

Lah, Melissa; Niranjan, Tejasvi; Srikanth, Sujata; Holloway, Lynda; Schwartz, Charles E; Wang, Tao; Weaver, David D

2016-04-01

We further evaluated a previously reported family with an apparently undescribed X-linked syndrome involving joint contractures, keloids, an increased optic cup-to-disc ratio, and renal stones to elucidate the genetic cause. To do this, we obtained medical histories and performed physical examination on 14 individuals in the family, five of whom are affected males and three are obligate carrier females. Linkage analysis was performed on all but one individual and chromosome X-exome sequencing was done on two affected males. The analysis localized the putative gene to Xq27-qter and chromosome X-exome sequencing revealed a mutation in exon 28 (c.4726G>A) of the filamin A (FLNA) gene, predicting that a conserved glycine had been replaced by arginine at amino acid 1576 (p.G1576R). Segregation analysis demonstrated that all known carrier females tested were heterozygous (G/A), all affected males were hemizygous for the mutation (A allele) and all normal males were hemizygous for the normal G allele. The data and the bioinformatic analysis indicate that the G1576R mutation in the FLNA gene is very likely pathogenic in this family. The syndrome affecting the family shares phenotypic overlap with other syndromes caused by FLNA mutations, but appears to be a distinct phenotype, likely representing a unique genetic syndrome. © 2016 Wiley Periodicals, Inc.

Cell surface localization of the 78 kD glucose regulated protein (GRP 78) induced by thapsigargin.

PubMed

Delpino, A; Piselli, P; Vismara, D; Vendetti, S; Colizzi, V

1998-01-01

In the present study it was found that the synthesis of the 78 kD glucose-regulated protein (GRP 78 or BIP) is vigorously induced in human rabdomiosarcoma cells (TE 671/RD) following both short-term (1 h) and prolonged (18 h) exposure to 100 nM thapsigargin (Tg). Flow cytometric analysis with a specific anti-GRP 78 polyclonal antibody showed that Tg-treated cells express the GRP 78 on the plasma membrane. Cell surface localization of the Tg-induced GRP 78 was confirmed by biotinylation of membrane-exposed proteins and subsequent isolation of the biotin-labelled proteins by streptavidin/agarose affinity chromatography. It was found that a fraction of the Tg-induced GRP 78 is present among the biotin-labelled, surface-exposed, proteins. Conversely, the GRP 78 immunoprecipitated from unfractionated lysates of Tg-treated and biotin-reacted cells was found to be biotinylated. This is the first report demonstrating surface expression of GRP 78 in cells exposed to a specific GRP 78-inducing stimulus.

Neuropathology of Alzheimer's disease.

PubMed

Perl, Daniel P

2010-01-01

Alois Alzheimer first pointed out that the disease which would later bear his name has a distinct and recognizable neuropathological substrate. Since then, much has been added to our understanding of the pathological lesions associated with the condition. The 2 primary cardinal lesions associated with Alzheimer's disease are the neurofibrillary tangle and the senile plaque. The neurofibrillary tangle consists of abnormal accumulations of abnormally phosphorylated tau within the perikaryal cytoplasm of certain neurons. The senile plaque consists of a central core of beta-amyloid, a 4-kD peptide, surrounded by abnormally configured neuronal processes or neurites. Other neuropathological lesions are encountered in cases of Alzheimer's disease, but the disease is defined and recognized by these 2 cardinal lesions. Other lesions include poorly understood changes such as granulovacuolar degeneration and eosinophilic rodlike bodies (Hirano bodies). The loss of synaptic components is a change that clearly has a significant impact on cognitive function and represents another important morphological alteration. It is important to recognize that distinguishing between Alzheimer's disease, especially in its early stages, and normal aging may be very difficult, particularly if one is examining the brains of patients who died at an advanced old age. It is also noted that instances of pure forms of Alzheimer's disease, in the absence of other coexistent brain disease processes, such as infarctions or Parkinson's disease-related lesions, are relatively uncommon, and this must be taken into account by researchers who employ postmortem brain tissues for research. (c) 2010 Mount Sinai School of Medicine.

Keloids

MedlinePlus

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Anti-inflammatory effect of intravenous immunoglobulin in comparison with dexamethasone in vitro: implication for treatment of Kawasaki disease.

PubMed

Makata, Haruyuki; Ichiyama, Takashi; Uchi, Ryutaro; Takekawa, Tsuyoshi; Matsubara, Tomoyo; Furukawa, Susumu

2006-08-01

High-dose intravenous immunoglobulin (IVIG) is a well-established standard therapy for Kawasaki disease (KD) that reduces the risk of developing coronary artery aneurysms. On the other hand, some reports have recommended an alternative therapy with steroids for KD patients. In this study we investigated the anti-inflammatory effect of IVIG in comparison with dexamethasone at clinical doses in vitro. High-dose IVIG inhibited tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear factor-kappaB (NF-kappaB) to a greater degree than dexamethasone in human monocytic U937 cells and human coronary arterial endothelial cells (HCAEC), but not in human T lymphocytic Jurkat cells. IVIG was more potent than dexamethasone in reducing the expression of CD16 (FcgammaRIII) in human monocytic THP-1 cells stimulated with lipopolysaccharide and in Jurkat cells stimulated with dimethyl sulfoxide. In HCAEC exposed to TNF-alpha, IVIG and dexamethasone inhibited interleukin-6 production to a similar degree, whereas the expression of E-selectin was inhibited more strongly by IVIG. Our results show that high-dose IVIG inhibits the activation of monocytes/macrophages and coronary arterial endothelial cells more strongly than that of T cells, whereas dexamethasone inhibits the activation of all three cell types. These findings suggest that IVIG or dexamethasone therapy should be chosen to match the types of cells that are activated during acute KD.

Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G.

PubMed

Ogata, Shohei; Shimizu, Chisato; Franco, Alessandra; Touma, Ranim; Kanegaye, John T; Choudhury, Biswa P; Naidu, Natasha N; Kanda, Yutaka; Hoang, Long T; Hibberd, Martin L; Tremoulet, Adriana H; Varki, Ajit; Burns, Jane C

2013-01-01

Although intravenous immunoglobulin (IVIG) is highly effective in Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG. We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I levels were measured by ELISA. There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively). Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.

Hyperplastic corneal pannus: an immunohistochemical analysis and review.

PubMed

Jakobiec, Frederick A; Stacy, Rebecca C; Mendoza, Pia R; Chodosh, James

2014-01-01

An exuberant corneal pannus usually develops in adults with a history of surgery or trauma in the anterior central stroma and appears as a glistening, vascularized, moderately elevated, well circumscribed white nodule. We describe a 78-year-old woman with such a pannus, which in the past has typically been referred to as keloidal or hypertrophic. The involved eye had only light perception, and she underwent a penetrating keratoplasty that improved her vision to 20/100. Histopathologic and immunohistochemical evaluations of a the specimen disclosed a reactive spindle cell stromal proliferation of myofibroblasts that were smooth muscle actin positive with a low Ki67 proliferation index. Desmin, caldesmon, and calponin were negative, in keeping with the incomplete myofilamentary differentiation of a myofibroblast. There was a generous admixture of CD68/163-positive histiocytes and dispersed C3/5-positive T-lymphocytes. An absence of CD138- and IgG4-positive plasma cells ruled out an IgG4-related disease. For a lesion to be keloidal, the collagen must have a thick hyaline character, sharp edges, and a sparsity of intervening cells and vessels. A hypertrophic pannus would be composed of large swollen cells not necessarily increased in number. We therefore recommend adoption of the term hyperplastic for lesions like that described here because of the obvious increase in cellularity from proliferating myofibroblasts and the lack of true keloidal collagen. Copyright © 2014 Elsevier Inc. All rights reserved.

Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation

PubMed Central

Hatfield, Paul; Prestwich, Robin JD; Shaffer, Richard E; Taylor, Roger E

2015-01-01

Most radiotherapy (RT) involves the use of high doses (>50 Gy) to treat malignant disease. However, low to intermediate doses (approximately 3–50 Gy) can provide effective control of a number of benign conditions, ranging from inflammatory/proliferative disorders (e.g. Dupuytren's disease, heterotopic ossification, keloid scarring, pigmented villonodular synovitis) to benign tumours (e.g. glomus tumours or juvenile nasopharyngeal angiofibromas). Current use in UK RT departments is very variable. This review identifies those benign diseases for which RT provides good control of symptoms with, for the most part, minimal side effects. However, exposure to radiation has the potential to cause a radiation-induced cancer (RIC) many years after treatment. The evidence for the magnitude of this risk comes from many disparate sources and is constrained by the small number of long-term studies in relevant clinical cohorts. This review considers the types of evidence available, i.e. theoretical models, phantom studies, epidemiological studies, long-term follow-up of cancer patients and those treated for benign disease, although many of the latter data pertain to treatments that are no longer used. Informative studies are summarized and considered in relation to the potential for development of a RIC in a range of key tissues (skin, brain etc.). Overall, the evidence suggests that the risks of cancer following RT for benign disease for currently advised protocols are small, especially in older patients. However, the balance of risk vs benefit needs to be considered in younger adults and especially if RT is being considered in adolescents or children. PMID:26462717

Kawasaki disease and toxic shock syndrome--at last the etiology is clear?

PubMed

Curtis, Nigel

2004-01-01

A decade after the superantigen hypothesis for KD was first suggested, it has still not been either proven or refuted conclusively. Although initial optimism for the hypothesis was quashed by a series of published papers apparently refuting the idea, in the last few years there have been a number of good studies providing evidence in support of the superantigen hypothesis. Whether this renewed enthusiasm is justified will hopefully become clear in the near future. Ultimately, accurate diagnosis, more targeted treatment, and preventative strategies depend on the unraveling of the immunopathogenesis of this disease.

The Ketogenic Diet and Sport: A Possible Marriage?

PubMed

Paoli, Antonio; Bianco, Antonino; Grimaldi, Keith A

2015-07-01

The ketogenic diet (KD) is used widely as a weight loss strategy and, more rarely, as therapy for some diseases. In many sports, weight control is often necessary (boxing, weightlifting, wrestling, etc.), but the KD usually is not considered. Our hypothesis is that KD might be used to achieve fat loss without affecting strength/power performance negatively.

Fever without a source: evolution of a diagnosis from Kawasaki disease to acute myelogenous leukaemia.

PubMed

Lee, Begem; Kofman, Christine D; Tremoulet, Adriana H; Kuo, Dennis John

2017-05-06

A previously healthy 11-month-old male patient presented with fever, abdominal pain and irritability. As part of an extensive evaluation for the cause of his fevers, an echocardiogram was performed and showed mildly dilated coronary arteries, leading to a diagnosis of incomplete Kawasaki disease (KD). He was treated with intravenous immunoglobulin (IVIG), defervesced and was discharged home. Two weeks later, he presented with anaemia initially attributed to haemolytic anaemia secondary to IVIG and received a red blood cell transfusion. However, his anaemia recurred 2  weeks later with leucocytosis, prompting a bone marrow aspirate 4  weeks after his diagnosis of KD. This demonstrated acute myelogenous leukaemia most consistent with acute megakaryocytic leukaemia. This case highlights the potentially subtle presentation of acute leukaemia and the need to keep an open mind and reconsider the initial diagnosis as new information comes to light in the care of an ill child. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of secondary carbon supplement on biofilm-mediated biodegradation of naphthalene by mutated naphthalene 1, 2-dioxygenase encoded by Pseudomonas putida strain KD9.

PubMed

Dutta, Kunal; Shityakov, Sergey; Khalifa, Ibrahim; Mal, Arpan; Moulik, Satya Priya; Panda, Amiya Kumar; Ghosh, Chandradipa

2018-05-18

Polycyclic aromatic hydrocarbons (PAHs) belong to a diverse group of environmental pollutants distributed ubiquitously in the environment. The carcinogenic properties of PAHs are the main causes of harm to human health. The green technology, biodegradation have become convenient options to address the environmental pollution. In this study, we analyzed the biodegradation potential of naphthalene with secondary carbon supplements (SCSs) in carbon deficient media (CSM) by Pseudomonas putida strain KD9 isolated from oil refinerary waste. The rigid-flexible molecular docking method revealed that the mutated naphthalene 1,2-dioxygenase had lower affinity for naphthalene than that found in wild type strain. Moreover, analytical methods (HPLC, qRT-PCR) and soft agar chemotaxis suggest sucrose (0.5 wt%) to be the best chemo-attractant and it unequivocally caused enhanced biodegradation of naphthalene (500 mg L -1 ) in both biofilm-mediated and shake-flask biodegradation methods. In addition, the morphological analysis detected from microscopy clearly showed KD9 to change its size and shape (rod to pointed) during biodegradation of naphthalene in CSM as sole source of carbon and energy. The forward versus side light scatter plot of the singlet cells obtained from flow cytometry suggests smaller cell size in CSM and lower florescence intensity of the total DNA content of cells. This study concludes that sucrose may be used as potential bio-stimulation agent. Copyright © 2018 Elsevier B.V. All rights reserved.