Superoxide dismutase from Helicobacter pylori suppresses the production of pro-inflammatory cytokines during in vivo infection

Abstract

Background

Helicobacter pylori has undergone considerable adaptation to allow chronic persistence within the gastric environment. While H. pylori-associated diseases are driven by an excessive inflammation, severe gastritis is detrimental to colonization by this pathogen. Hence, H. pylori has developed strategies to minimize the severity of gastritis it triggers in its host. Superoxide dismutase (SOD) is well known for its role in protecting against oxidative attack; less recognized is its ability to inhibit immunity, shown for SOD from mammalian sources and those of some bacterial species. This study examined whether H. pylori SOD (HpSOD) has the ability to inhibit the host immune response to these bacteria.

Materials and Methods

The ability of recombinant HpSOD to modify the response to LPS was measured using mouse macrophages. A monoclonal antibody against HpSOD was generated and injected into H. pylori-infected mice.

Results

Addition of HpSOD to cultures of mouse macrophages significantly inhibited the pro-inflammatory cytokine response to LPS stimulation. A monoclonal antibody was generated that was specific for SOD from H. pylori. When injected into mice infected with H. pylori for 3 months, this antibody was readily detected in both sera and gastric tissues 5 days later. While treatment with anti-HpSOD had no effect on H. pylori colonization at this time point, it significantly increased the levels of a range of pro-inflammatory cytokines in the gastric tissues. This did not occur with antibodies against other antioxidant enzymes.

Conclusions

SOD from H. pylori can inhibit the production of pro-inflammatory cytokine during in vivo infection.

http://ift.tt/2C9tbcf

Management of actinic keratosis at specific body sites in patients at high risk of carcinoma lesions: expert consensus from the AKTeam™ of expert clinicians

Abstract

Background

Actinic keratoses (AK) arise on sun-exposed regions of the skin. If left untreated, AK may progress to invasive squamous cell carcinoma (SCC), although the rate of progression is low. A practical treatment algorithm for the treatment of AK in standard situations has been published by the AKTeam^™ expert panel. However, management of particular situations of AK with increasing/higher carcinoma risk or AK progressing into carcinomas with increased aggressiveness due to their anatomical location (risky areas), or in patients with an increased risk of SCC requires further discussion. These include AK on the dorsal hands, forearms, legs, periorbital region, eyelids, ears, or lips, and organ transplant recipients, patients undergoing treatment with carcinogenic agents, and patients with chronic lymphocytic leukemia.

Objective

The main objective was to propose therapeutic strategies for the treatment of AK located in risky areas, and in patients with more invasive/aggressive lesions and a higher risk of progression to SCC.

Methods

A systematic review of the literature was initially performed, and results were discussed by the experts to propose best management practices in specific situations. Finally, adapted management strategies for AK occurring in risky areas and in high-risk patients are presented, taking into account the experts' own clinical experience and current guidelines.

Results

In most of these 'at-risk' situations, patients can be treated according to the AKTeam^™ treatment algorithm. Difficult-to-treat lesions should be treated more aggressively due to their higher risk of transformation. For patients with skin that is highly susceptible to actinic damage, monitoring and sun-protection strategies are mandatory and patients should undergo more regular follow up. Further assessment of newer therapies in clinical trials is necessary to determine optimal treatment conditions.

Conclusion

This expert consensus provides guidance for the management of AK in risky body sites, and in patients with an increasing/higher risk for SCCs.

This article is protected by copyright. All rights reserved.

http://ift.tt/2C91RLn

Value of complex evoked auditory brainstem response in patients with post-stroke aphasia (prospective study)

Publication date: Available online 12 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): S. Mourad, M. Abd Al-Ghaffar, Mohamed Al-Amir Bassiony, G. Fawzi
ObjectiveTo evaluate the perception of complex ABR (C-ABR) in aphasic patients and to compare it before and 3 months after management of stroke.MethodologyA prospective study was conducted on 30 aphasic patients using C-ABR. The results were compared within 2 weeks post-stroke and 3 months after management. The results of aphasic patients were compared with normal subjects.ResultsThe seven C-ABR waves regarding the onset (wave V and A), offset (peak O), transition (peak C) and frequency following responses (peak D, E and F) were identified in all participants. There was a statistically significant difference in C-ABR latencies between control and study group in the waves D, E, F and O, this means that aphasic patients exhibited abnormal neural synchrony affecting the source elements (fundamental frequency) (waves D, E, F and O) however there was no effect on the filter elements (transients).ConclusionAphasic patients exhibited abnormal neural synchrony affecting the source elements (waves D, E, F and O) however there was no effect on the filter elements (transients).



http://ift.tt/2AyNq5Y

Melanotic neuroectodermal tumor of infancy (MNTI) of the head and neck: A French multicenter study

Publication date: Available online 12 December 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Audrey Moreau, Louise Galmiche, Veronique Minard-Colin, Martin Rachwalski, Kahina Belhous, Daniel Orbach, Aline Joly, Arnaud Picard, Natacha Kadlub
ObjectivesMelanotic neuroectodermal tumor of infancy (MNTI) of the head and neck is a rare entity with uncertain clinical behavior. Radical surgical resection is the current recommended treatment, however this can cause severe aesthetic and functional sequelae. The aim of this study was to clinically characterize MNTIs and to stratify risk factors that may influence locoregional recurrence.MethodsA retrospective multicenter study, including 11 patients from eight centers with a confirmed diagnosis of MNTI, was conducted. Epidemiological, clinical, radiological, pathological, and immunohistochemical examinations were reviewed. A statistical analysis using a t-test was conducted to calculate parameters correlating with tumor recurrence.ResultsMNTIs mainly occurred in the maxilla, with a mean age at diagnosis of 3.18 months (range: 0–6 months). Primary surgery was performed on 10 patients, with a clear margin resection on two patients. Overall recurrence rate was 27% with a survival of 100% at time of follow-up. No statistical correlation between recurrence rate, age at diagnosis, localization, resection margins, and pathological and immunohistochemical characteristics could be established.ConclusionIn our study, locoregional tumor recurrence did not seem to correlate with resection margins, so a conservative surgical approach may need to be considered to avoid functional and aesthetic sequelae.



http://ift.tt/2iXioJR

Acral melanoma foot lesions. Part 2: clinical presentation, diagnosis, and management

Summary

Acral melanoma (AM) is a rare subtype of cutaneous malignant melanoma found on acral skin, primarily on the soles of the feet. Although rare, it is the most common subtype of melanoma found in patients of African or Asian ethnicity and has a poor prognosis, often because of the more advanced stage of presentation at diagnosis. In the second of this two-part series, we review the clinical presentation, histopathology, diagnosis and management of AM. Clinically, AM presents as a variegated lesion with blue–black pigment and irregular borders on acral skin. A parallel-ridge pattern is a very specific dermoscopic finding for AM. The differential diagnoses of AM include acral naevus, pyoderma gangrenosum, pyogenic granuloma, verrucous carcinoma and peripheral neuropathy-induced foot ulcers. If there is a clinical suspicion of AM, an excisional biopsy should be taken. Once diagnosis is confirmed by histology, surgical excision is the standard treatment. Overall, dermoscopy and histopathology are key tools in the diagnosis of AM. A greater emphasis on melanoma screening and awareness is essential in minority populations to improve survival outcomes in AM.

http://ift.tt/2o0AGiT

MPO-ANCA associated vasculitis with mononeuritis multiplex following influenza vaccination

Although influenza vaccines are generally safe and effective, a variety of autoimmune phenomena have been reported after vaccination over the past years, such as Guillain–Barre syndrome, rheumatoid arthritis, ...

http://ift.tt/2BYXJww

Expression and Significance of Cytokeratin 7, a Squamocolumnar Junction Marker, in Head and Neck Squamous Cell Carcinoma

Abstract

The favorable features of high-risk human papillomavirus (HPV) in the head and neck are limited to those harboring transcriptionally-active HPV, which occur predominantly in the oropharynx (OP). Factors rendering the OP susceptible to HPV oncogenesis are largely unexplored. The role of cytokeratin 7 (CK7) in predisposition to HPV and cancer in the cervix has been evaluated. However, its significance in the H&N is unknown. CK7 immunohistochemistry was performed on a tissue microarray cohort of OP and non-oropharyngeal (NOP) squamous cell carcinomas (SCC) with known clinical follow-up and HPV E6/7 mRNA status. Expression was graded based on the distribution (1 ≤ 33%, 2 = 33–66%, 3 ≥ 66%) and intensity (1 = weak, 2 = strong) with combined score of ≥ 2 considered positive. Survival analysis was performed. Seventy-four NOPSCCs and 204 OPSCCs were studied. HPV was positive in 2.7% of NOPSCCs and 70.9% of OPSCCs. CK7 was positive in 23.0% of OPSCCs and 14.8% of NOPSCCs (p = 0.2), and in 24.1% of HPV positive versus 17.2% of negative patients (p = 0.2). There was no correlation with age, race, gender, HPV status, histologic type, tumor subsite, treatment, stage, or co-morbidities, and CK7 expression was not significantly associated with overall or disease specific survival. In our series, CK7 is positive in ~ 25% of H&N SCCs, although usually only focally. While CK7 has been suspected to be overexpressed selectively in HPV-related OPSCCs due to their origination from tonsillar crypt epithelium, we did not find any significant difference by anatomic H&N subsite, nor by HPV status, for its expression and found no association with patient survival.

http://ift.tt/2z4SJIb

Lactose intolerance and gastrointestinal cow’s milk allergy in infants and children – common misconceptions revisited

Lactose is the main carbohydrate in human and mammalian milk. Lactose requires enzymatic hydrolysis by lactase into D-glucose and D-galactose before it can be absorbed. Term infants express sufficient lactase ...

http://ift.tt/2AyWVCo

Expression and Significance of Cytokeratin 7, a Squamocolumnar Junction Marker, in Head and Neck Squamous Cell Carcinoma

Abstract

The favorable features of high-risk human papillomavirus (HPV) in the head and neck are limited to those harboring transcriptionally-active HPV, which occur predominantly in the oropharynx (OP). Factors rendering the OP susceptible to HPV oncogenesis are largely unexplored. The role of cytokeratin 7 (CK7) in predisposition to HPV and cancer in the cervix has been evaluated. However, its significance in the H&N is unknown. CK7 immunohistochemistry was performed on a tissue microarray cohort of OP and non-oropharyngeal (NOP) squamous cell carcinomas (SCC) with known clinical follow-up and HPV E6/7 mRNA status. Expression was graded based on the distribution (1 ≤ 33%, 2 = 33–66%, 3 ≥ 66%) and intensity (1 = weak, 2 = strong) with combined score of ≥ 2 considered positive. Survival analysis was performed. Seventy-four NOPSCCs and 204 OPSCCs were studied. HPV was positive in 2.7% of NOPSCCs and 70.9% of OPSCCs. CK7 was positive in 23.0% of OPSCCs and 14.8% of NOPSCCs (p = 0.2), and in 24.1% of HPV positive versus 17.2% of negative patients (p = 0.2). There was no correlation with age, race, gender, HPV status, histologic type, tumor subsite, treatment, stage, or co-morbidities, and CK7 expression was not significantly associated with overall or disease specific survival. In our series, CK7 is positive in ~ 25% of H&N SCCs, although usually only focally. While CK7 has been suspected to be overexpressed selectively in HPV-related OPSCCs due to their origination from tonsillar crypt epithelium, we did not find any significant difference by anatomic H&N subsite, nor by HPV status, for its expression and found no association with patient survival.

http://ift.tt/2z4SJIb

Statistical models to predict adverse perioperative outcomes: A case for longer follow up time frames

Large datasets have become available and widely adopted by perioperative medicine researchers in the last decade [1–3]. The use of electronic medical records has facilitated massive data collection not only by single institutions, but also by multicenter initiatives [4–6]. Large datasets enabled the evaluation of infrequent (but important) perioperative outcome with the expectation that interventions could have been implemented to improve the care of patients undergoing surgical procedures.

http://ift.tt/2nSUxAh

Prognosticating hearing outcome in patients with idiopathic sudden sensorineural hearing loss by means of otoacoustic emissions and auditory brainstem response

Masoud Motasaddi Zarandy, MD; Mohammad Taghi Khorsandi Ashtiani, MD; Shahin Bastaninejad, MD; Sasan Dabiri Satri, MD; Sevil Nasirmohtaram, MD; Nourullah Agha Ebrahimi, BSC

Abstract

This is an analytic-descriptive study, parallel with a randomized, controlled trial performed at Amir'Alam Hospital, a tertiary referral center, with the aim of evaluating the correlation between otoacoustic emission (OAE) and auditory brainstem response (ABR) findings with hearing outcome after treatment of idiopathic sudden sensorineural hearing loss (SSNHL). Sixty patients with idiopathic SSNHL who presented to the emergency services and otology clinics between 2012 and 2014, and whose symptoms had begun <10 days previously, enrolled in this study. Before commencing treatment, distortion-product OAE (DP-OAE) and ABR were performed for all patients. They also underwent magnetic resonance imaging ± gadolinium. Therapeutic intervention was done in a parallel randomized, controlled trial, and responders to the medical therapy were selected for our final analysis. There was no significant correlation between the OAE record and responsiveness to treatment, but there was a correlation between ABR presence and the probability of responsiveness in patients with profound hearing loss who responded to medical therapy and had at least wave V ABR. However, in those who had no recorded wave, the response to treatment was variable. In conclusion, in patients with profound hearing loss, studying the waves of ABR could be a factor in predicting hearing loss resolution after treatment.

ENT Journal provides full text articles to our registered members.
Please log in or sign up for a FREE membership to view the full content:

• REGISTER AS A MEMBER
• If you are already registered, SIGN IN

You may also like to:

• Sign Up For The Free eNewsletter

http://ift.tt/2iZF6kl

Endoscopic endonasal management of recurrent maxillary mucoceles using biliary T-tube stenting

Noritsugu Ono, MD; Shin Ito, MD; Hirotomo Homma, MD; Hiroko Okada, MD; Junko Murata, MD; Katsuhisa Ikeda, MD, PhD

Abstract

Mucoceles of the paranasal sinus can be managed endoscopically with an extremely low recurrence rate. Frontal sinus mucoceles can sometimes be prevented from closing and reforming by stenting, which to the best of our knowledge has not yet been reported in the maxillary sinus. We describe the cases of 5 patients-3 men and 2 women, aged 47 to 75 years (mean: 59.6)-with a recurrent and intractable maxillary sinus mucocele that was managed with biliary T-tube stenting. The indications for stenting included recurrent episodes of mucocele with or without a lateral location with a relatively thick bony wall. A latex rubber pediatric biliary T-tube was endoscopically inserted through a window opening into the marsupialized mucocele. The stent was removed 6 to 14 months postoperatively in 4 cases; in the other case, the stent remained adequately positioned for 35 months. None of the patients experienced signs or symptoms of recurrence. We conclude that a T-tube stent can be used successfully to maintain long-term patency in patients with a recurrent and intractable maxillary mucocele, with patency being maintained even after removal of the stent.

ENT Journal provides full text articles to our registered members.
Please log in or sign up for a FREE membership to view the full content:

• REGISTER AS A MEMBER
• If you are already registered, SIGN IN

You may also like to:

• Sign Up For The Free eNewsletter

http://ift.tt/2Bi8ZqS

Head and neck surgical reconstruction in Operation Iraqi Freedom and Operation Enduring Freedom-Afghanistan: A systematic review

Samantha J. Mikals, MD; Joshua M. Jabaut, MD; Art A. Ambrosio, MD

Abstract

Historically, head and neck injuries constituted 16 to 20% of all nonfatal combat injuries. However, advances in body and vehicle armor in the context of the use of ambushes and improvised explosive devices by enemy combatants have resulted in fewer fatalities from head and neck wounds, and thus the incidence of nonfatal head and neck injuries has risen to as high as 52%. Despite this increase, data regarding specific injury distributions, surgical cases, and approaches to repair are lacking in the current literature. We conducted a study to systematically review the current literature regarding head and neck injuries and reconstructions during Operation Iraqi Freedom and Operation Enduring Freedom-Afghanistan. We found 44 articles that met our inclusion criteria. These articles covered 17,461 head and neck wounds sustained by 12,105 patients. Superficial soft-tissue facial injuries were most common wounds (31.7% of cases), followed by wounds to the neck (25.2%) and midface (17.9%). The 44 articles listed 5,122 discrete surgical reports covering 5,758 procedures. Of these procedures, simple facial laceration repairs (25.2%) and ophthalmologic surgeries (12.1%) were the most common soft-tissue repairs, and mandibular reconstructions (11.3%) were the most common type of bony reconstruction. Major flap reconstructions for coverage were required in only 0.4% of procedures. This information will be valuable for educating those involved in otolaryngology training programs, as well as civilian otolaryngologists regarding the types of injury patterns they should expect to see and treat in the returning veteran population.

ENT Journal provides full text articles to our registered members.
Please log in or sign up for a FREE membership to view the full content:

• REGISTER AS A MEMBER
• If you are already registered, SIGN IN

You may also like to:

• Sign Up For The Free eNewsletter

http://ift.tt/2iXfODq

Clouds of different colors: A prospective look at head and neck surgical resident call experience

Jonathan Melzer, MD, LCDR, MC, USN

Abstract

Graduate medical education programs typically set up call under the assumption that residents will have similar experiences. The terms black cloud and white cloud have frequently been used to describe residents with more difficult (black) or less difficult (white) call experiences. This study followed residents in the department of head and neck surgery during call to determine whether certain residents have a significantly different call experience than the norm. It is a prospective observational study conducted over 16 months in a tertiary care center with a resident training program in otolaryngology. Resident call data on total pages, consults, and operative interventions were examined, as well as subjective survey data about sleep and perceived difficulty of resident call. Analysis showed no significant difference in call activity (pages, consults, operative interventions) among residents. However, data from the resident call surveys revealed perceived disparities in call difficulty that were significant. Two residents were clearly labeled as black clouds compared to the rest. These residents did not have the highest average number of pages, consults, or operative interventions. This study suggests that factors affecting call perception are outside the objective, absolute workload. These results may be used to improve resident education on sleep training and nighttime patient management in the field of otolaryngology and may influence otolaryngology residency programs.

ENT Journal provides full text articles to our registered members.
Please log in or sign up for a FREE membership to view the full content:

• REGISTER AS A MEMBER
• If you are already registered, SIGN IN

You may also like to:

• Sign Up For The Free eNewsletter

http://ift.tt/2BdPH6d

Intracranial abscess formation following sphenoid sinus occlusion with nasoseptal flap skull base reconstruction: A cautionary tale

George S. Tarasidis, MD; Jeremiah A. Alt, MD, PhD; Richard R. Orlandi, MD

Abstract

The formation of an intracranial abscess secondary to sphenoid sinus occlusion after nasoseptal flap skull base reconstruction has not been previously described. We report such a case that occurred at our institution in a 23-year-old man who underwent flap reconstruction for a cerebrospinal fluid leak. We determined that occlusion of the sphenoid sinus outflow might have played a role in this complication. The patient was treated via a combined surgical and medical approach that entailed a bur-hole craniotomy and endoscopic debridement followed by administration of an intravenous antibiotic. The patient recovered without long-term deficit. When closing a defect of the posterior ethmoid and sphenoid skull base, especially with a pedicled graft, care must be taken to reduce the potential for retention of secretions and blood because this may lead to an intracranial complication.

ENT Journal provides full text articles to our registered members.
Please log in or sign up for a FREE membership to view the full content:

• REGISTER AS A MEMBER
• If you are already registered, SIGN IN

You may also like to:

• Sign Up For The Free eNewsletter

http://ift.tt/2iW1tqY

Preoperative evaluation and intraoperative protection of the facial nerve in congenital aural atresia

Jie Li, MD; Shouqin Zhao, PhD; Lin Yang, MD; Yi Li, PhD; Xiaobo Ma, PhD; Danni Wang, PhD; Ran Ren, MD; Ying Li, MD

Abstract

We conducted a prospective study to assess the value of high-resolution computed tomography (HRCT) in identifying facial nerve variations in patients with congenital aural atresia and to determine how they affect otologic reconstruction surgery. Our study population was made up of 65 patients (69 ears) aged 6 to 22 years (mean: 13.7) without regard to sex. They were classified into three groups according to their scores on the Jahrsdoerfer grading scale: 46 ears scored 8 or more, 18 had a score of 6 or 7, and 5 scored 5 or less. The course of each facial nerve as determined intraoperatively was compared with the preoperative HRCT findings. HRCT revealed that in most of the facial nerves, the tympanic segments overlapped the oval window partly or completely; this was confirmed by surgical findings in most cases. Three of the 69 facial nerves (4.3%) were bifurcated. It is interesting that in 1 ear in which the facial nerve completely covered the oval window, the angle of the second genu was acute, exhibiting a "sharp turn." We conclude that HRCT is undoubtedly of value in identifying the course of the facial nerve and is of critical importance in helping surgeons make correct decisions in otologic reconstruction surgery.

ENT Journal provides full text articles to our registered members.
Please log in or sign up for a FREE membership to view the full content:

• REGISTER AS A MEMBER
• If you are already registered, SIGN IN

You may also like to:

• Sign Up For The Free eNewsletter

http://ift.tt/2BhpSlu

Nasopharyngeal papillary adenocarcinoma

Lester D. Thompson, MD

Nasopharyngeal papillary adenocarcinoma may appear grossly as an exophytic, nodular, or polypoid mass, sometimes gritty if psammoma bodies are present.

ENT Journal provides full text articles to our registered members.
Please log in or sign up for a FREE membership to view the full content:

• REGISTER AS A MEMBER
• If you are already registered, SIGN IN

You may also like to:

• Sign Up For The Free eNewsletter

http://ift.tt/2iZ1LNU

Multidisciplinary management of a giant cervico-mediastinal liposarcoma: A case report and literature review

Andrea Galli, MD; Leone Giordano, MD; Piergiorgio Muriana, MD; Alessandro Bandiera, MD; Giampiero Negri, MD; Piero Zannini, MD; Mario Bussi, MD

Abstract

Liposarcomas are rare mesenchymal tumors that usually develop in lower extremities or retroperitoneum; cervico-mediastinal presentation is quite uncommon. These neoplasms are commonly diagnosed at a late stage because they remain asymptomatic until nearby structures are compressed. This makes radical excision particularly challenging. To date, alternative chemoradiotherapy protocols have not yet been standardized. We report a case of a 55-year-old man with a right laterocervical mass and without substantial symptoms. Fine-needle aspiration cytology results were compatible with a well-differentiated liposarcoma. Contrast-enhanced magnetic resonance imaging revealed the magnitude of the mass, which was expanding into the mediastinum; displacing the trachea, esophagus, cervical neurovascular bundle, and thoracic aorta; and encasing the brachiocephalic artery. Compression of the left brachiocephalic vein resulted in a focal enhancement spot in the fourth liver segment, the expression of superior vena cava compression, which can promote the development of collateral venous pathways, such as the caval-mammary-phrenic-hepatic capsule-portal venous pathway. The mass was successfully excised by a team of surgical subspecialists (otorhinolaryngologists and thoracic, cardiac, and vascular surgeons). Adjuvant tomotherapy was administered to increase local disease control. The patient remained disease-free 38 months postoperatively. This case underlines the importance of accurate preoperative radiologic evaluation in patients presenting with neck masses but without substantial symptoms. Because of the involvement of many critical structures, the cooperation of many surgical subspecialties is mandatory to achieve a satisfying oncologic outcome.

ENT Journal provides full text articles to our registered members.
Please log in or sign up for a FREE membership to view the full content:

• REGISTER AS A MEMBER
• If you are already registered, SIGN IN

You may also like to:

• Sign Up For The Free eNewsletter

http://ift.tt/2BfZ4Cl

Skin necrosis in a magnet-based bone-conduction implant

Sara Gallant, MD; Judy Lee, MD; Daniel Jethanamest, MD

Patients with complicated wound sites or multiple surgeries should be counseled to carefully monitor their skin as they have reduced sensation.

ENT Journal provides full text articles to our registered members.
Please log in or sign up for a FREE membership to view the full content:

• REGISTER AS A MEMBER
• If you are already registered, SIGN IN

You may also like to:

• Sign Up For The Free eNewsletter

http://ift.tt/2iXq6Ul

Proliferative pilomatricoma of the eyebrow in a 94-year-old patient

Christopher P. Nyte, DO

While pilomatricomas affect both the young and elderly, it is the elderly that tend to experience the advancing proliferative tumor type.

ENT Journal provides full text articles to our registered members.
Please log in or sign up for a FREE membership to view the full content:

• REGISTER AS A MEMBER
• If you are already registered, SIGN IN

You may also like to:

• Sign Up For The Free eNewsletter

http://ift.tt/2Bhy998

Expression and Significance of Cytokeratin 7, a Squamocolumnar Junction Marker, in Head and Neck Squamous Cell Carcinoma

Abstract

The favorable features of high-risk human papillomavirus (HPV) in the head and neck are limited to those harboring transcriptionally-active HPV, which occur predominantly in the oropharynx (OP). Factors rendering the OP susceptible to HPV oncogenesis are largely unexplored. The role of cytokeratin 7 (CK7) in predisposition to HPV and cancer in the cervix has been evaluated. However, its significance in the H&N is unknown. CK7 immunohistochemistry was performed on a tissue microarray cohort of OP and non-oropharyngeal (NOP) squamous cell carcinomas (SCC) with known clinical follow-up and HPV E6/7 mRNA status. Expression was graded based on the distribution (1 ≤ 33%, 2 = 33–66%, 3 ≥ 66%) and intensity (1 = weak, 2 = strong) with combined score of ≥ 2 considered positive. Survival analysis was performed. Seventy-four NOPSCCs and 204 OPSCCs were studied. HPV was positive in 2.7% of NOPSCCs and 70.9% of OPSCCs. CK7 was positive in 23.0% of OPSCCs and 14.8% of NOPSCCs (p = 0.2), and in 24.1% of HPV positive versus 17.2% of negative patients (p = 0.2). There was no correlation with age, race, gender, HPV status, histologic type, tumor subsite, treatment, stage, or co-morbidities, and CK7 expression was not significantly associated with overall or disease specific survival. In our series, CK7 is positive in ~ 25% of H&N SCCs, although usually only focally. While CK7 has been suspected to be overexpressed selectively in HPV-related OPSCCs due to their origination from tonsillar crypt epithelium, we did not find any significant difference by anatomic H&N subsite, nor by HPV status, for its expression and found no association with patient survival.

http://ift.tt/2z4SJIb

Melanotic neuroectodermal tumor of infancy (MNTI) of the head and neck: A French multicenter study

Melanotic neuroectodermal tumor of infancy (MNTI) of the head and neck is a rare entity with uncertain clinical behavior. Radical surgical resection is the current recommended treatment, however this can cause severe aesthetic and functional sequelae. The aim of this study was to clinically characterize MNTIs and to stratify risk factors that may influence locoregional recurrence.

http://ift.tt/2C8mx60

Classification of cutaneous manifestations in patients with non-celiac gluten sensitivity (NCGS) and wheat allergy (WA)

http://ift.tt/2AQ9INE

Mohs micrographic surgery and dermatopathology concordance; An analysis of 1421 Mohs cases over 17 years

Mohs micrographic surgery depends on the surgeon's ability to correctly interpret intraoperative frozen sectionsWe reviewed 1421 Mohs cases and 6407 slides for possible disagreement between fellowship trained-Mohs surgeons and dermatopathologists; the concordance rate was 99.79%Fellowship-trained Mohs surgeons are proficient at interpreting histopathology slides in the setting of Mohs micrographic surgery

http://ift.tt/2AOkeF1

Reply to: Comment on "Association of bullous pemphigoid with malignancy: A systematic review and meta-analysis”

http://ift.tt/2BXQjcZ

Association of Very Preterm Birth with Decreased Risk of Eczema: A Systematic Review and Meta-analysis

It is debated whether preterm infants are prone to developing eczema.This meta-analysis of 18 studies showed that very preterm birth is associated with a decreased risk of eczema.The underlying mechanisms of this association warrant further study.

http://ift.tt/2BVJpog

Metformin and skin cancer risk in Taiwanese patients with type 2 diabetes

Metformin, an antidiabetic drug, is associated with decreased cancer risk, but its effect on skin cancer is unknown.

http://ift.tt/2ANwjKt

Comparative study of volumetric changes and trabecular microarchitecture in human maxillary sinus bone augmentation with bioactive glass and autogenous bone graft: a prospective and randomized assessment

The aim of this study was to compare the volumetric changes and the new bone microarchitecture in human maxillary sinuses augmented with bioactive glass (Biogran) alone, bioactive glass combined with autogenous bone graft (1:1), or autogenous bone graft alone. Twelve maxillary sinuses were grafted with bioactive glass (group 1), nine with bioactive glass mixed with autogenous bone graft 1:1 (group 2), and 12 with autogenous bone graft (group 3). Patients underwent cone beam computed tomography 15days after the procedure to determine the initial volume of the graft (T1) and again 6 months later (T2).

http://ift.tt/2C6IGBH

Sequencing of bimaxillary surgery in the correction of vertical maxillary excess: retrospective study

The aim of this study was to evaluate the precision of bimaxillary surgery performed to correct vertical maxillary excess, when the procedure is sequenced with mandibular surgery first or maxillary surgery first. Thirty-two patients, divided into two groups, were included in this retrospective study. Group 1 comprised patients who received bimaxillary surgery following the classical sequence with repositioning of the maxilla first. Patients in group 2 received bimaxillary surgery, but the mandible was operated on first.

http://ift.tt/2nWgr5O

Increased ratio of pollock roe-specific IgE to salmon roe-specific IgE levels is associated with a positive reaction to cooked pollock roe oral food challenge

Publication date: Available online 11 December 2017
Source:Allergology International
Author(s): Eishi Makita, Noriyuki Yanagida, Sakura Sato, Tomoyuki Asaumi, Motohiro Ebisawa
BackgroundAnaphylaxis and immediate-type fish roe allergies have been reported worldwide, and, in Japan, fish roe is the sixth most common food allergen. No oral food challenges (OFCs) have used pollock roe (PR), which is reported to have high cross-reactivity with salmon roe (SR). Therefore, we administered an OFC using cooked PR to evaluate PR- and SR-specific immunoglobulin E (IgE) levels and allergic reactions in patients with PR sensitivity.MethodsThis retrospective study evaluating patient characteristics and responses to OFCs was conducted with 10–20 g of cooked PR, between April 2006 and November 2016.ResultsWe assessed 51 patients (median age: 6.8 years). All had PR sensitization, 6 (12%) with a history of immediate reactions to PR, and 18 (35%) of immediate reactions to SR. Median PR-specific and SR-specific IgE values were 3.4 kUA/L and 9.9 kUA/L, respectively. Seven patients (14%) had a positive OFC. There was no anaphylaxis. Induced symptoms were mild and included localized urticaria, throat pruritus, intermittent cough, and mild abdominal pain. We treated one patient with mild abdominal pain with oral antihistamines. There were no significant differences in history of immediate reaction to PR and PR-specific IgE titers between OFC-positive and OFC-negative patients, although significant differences were found for PR-specific IgE titers adjusted for SR-specific IgE (p = 0.025) and PR-specific IgE/SR-specific IgE ratio (p = 0.009).ConclusionsIncreased PR-specific IgE/SR-specific IgE ratio or PR-specific IgE levels adjusted for SR-specific IgE levels were risk factors for OFC positivity.



http://ift.tt/2jC2Uz0

Predictors for incidence of increased time spent in hospital after ambulatory surgery in children: a retrospective cohort study

Abstract

Purpose

Recently, pediatric ambulatory surgery has become common. However, for some of these patients, unplanned admission or prolonged hospital stay is also necessary, which can increase the mental burden on these patients. The aim of this study was to identify the predictors of the incidence of increased time spent in hospitals associated with pediatric ambulatory surgery.

Methods

Data were obtained from the medical and anesthetic records of 1087 consecutive patients aged < 18 years who underwent ambulatory surgery under general anesthesia. We defined the incidence of increased time spent in a hospital as a composite outcome of unplanned admission and prolonged hospital stay. Multivariate logistic regression analysis was used to examine the associations between the incidence of increased time spent in a hospital and 14 parameters including patient characteristics, anesthesia, and operative factors.

Results

Multivariate analysis identified American Society of Anesthesiologist Physical Status (ASA-PS), type of regional block, intraoperative fluid volume, and type of surgery as predictors for the incidence of increased time spent in a hospital. Specifically, caudal block compared to no regional block [odds ratio (OR) (95% confidence interval (CI)) = 0.44 (0.22–0.90)]; increasing intraoperative fluid volume [OR (95% CI) = 0.71 (0.55–0.92) in every increment of 5 ml/kg/h); and ear, nose, and throat (ENT) and urology surgery compared to other types of surgery [OR (95% CI) = 0.13 (0.03–0.64), and 3.93 (1.99–7.77), respectively] were identified as strong predictors.

Conclusions

This study found that the incidence of increased time spent in a hospital in pediatric ambulatory surgery was affected by the type of regional block, intraoperative fluid volume, type of surgery. Potentially modifiable factors, such as intraoperative fluid volume or type of regional block, should be further investigated in future prospective studies.

http://ift.tt/2BEwew4

The clinical significant of pre-surgical imaging in oral squamous cell carcinoma compared with lymph node status: a comparative retrospective study

Publication date: Available online 11 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Elias Mazzawi, Imad Abu El-naaj, Yasmine Ghantous, Salim Balan, Edmond Sabo, Adi Rachmiel, Yoav Leiser
AimThe accuracy and sensitivity of commonly used imaging modalities in evaluating oral cavity cancer was evaluated by comparing the pre-surgical radiological findings and the post-surgical pathological report.MethodsOral squamous cell carcinoma patients, who had undergone at least one imaging test 2 weeks before the surgery, were included. Radiological findings were compared with the dissected neck to assess the lymph node status. Sensitivity and specificity of the imaging modalities were calculated using the Chi-square test.ResultsSensitivities for detecting metastatic neck lymph nodes at a threshold of 1cm were 48% (P = 0.02) and 43.8% (P = 0.3) for CT and MRI respectively. Specificities were 76.3% and 70% respectively. As for the 1.5cm threshold sensitivities were 36% (P = 0.002) and 31.3% (P = 0.5) respectively, and specificities were 91.5% and 76.7% respectively. PET-CT was the most sensitive modality in the present study, with a P value 0.02.ConclusionThe different studied imaging modalities used for pre-operational neck staging are not sensitive enough and would lead to underdiagnoses of a respectful proportion of patients. Thus prophylactic neck dissection for occult neck disease is of extreme importance and remains the gold-standard for oral cancer treatment.



http://ift.tt/2jUkPhk

Relationship between sjögren's syndrome and periodontal status- a systematic review

Publication date: Available online 11 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Luana de Goés Soares, Ricardo Lopes Rocha, Elizabete Bagordakis, Endi Lanza Galvão, Dhelfeson Willya Douglas-de-Oliveira, Saulo Gabriel Moreira Falci
ObjectiveThis study aimed to evaluate if Sjögren's syndrome is related to periodontal status.Study DesignA systematic review was performed based on PRISMA (PROSPERO: CRD42017055202). The search was performed in the PubMed/MEDLINE, LILACS, Web of Science and Science Direct databases. Hand searches and gray literature were also performed. Three researchers independently selected studies, extracted data and assessed methodological quality. Studies that correlated primary and/or secondary SS, with plaque index, gingival index, probing depth and bleeding on probing were included. The risk of bias was estimated based on the Newcastle-Ottawa scale.ResultsSeventeen studies were included, and nine included in the meta-analysis, with a total of 518 and 544 patients, with and without Sjögren's Syndrome, respectively. The mean difference of plaque index (0.29; CI95% 0.17-0.41), gingival index (0.52; CI95% 0.14-0.89) and bleeding on probing (9.92; CI95%4.37-15.47) were larger in SS patients than controls. In primary SS (0.47; CI95% 0.10-0.83) and secondary SS (0.74 CI95% 0.10-1.38), only gingival index mean was larger than in control group. The majority of the included studies were judged as high risk of bias.ConclusionThe present review does not provide strong evidence to ensure that the periodontal status is affected by Sjögren's syndrome.



http://ift.tt/2krhKVn

Mastocytosis Becomes a 'Disease You Don't Want to Miss'

A novel drug designed specifically to target a mutation found in 90% of cases shows marked activity, and has already sparked an increase in interest in this disease.
Medscape Medical News

http://ift.tt/2BtxfHi

The Effect of Fecal Microbiota Transplantation on a Child with Tourette Syndrome

Tourette syndrome is a neuropsychiatric disorder with onset in childhood. New therapies are needed to effectively manage and treat this condition. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Here, we report a case in which fecal microbiota transplantation (FMT) is used to treat a child with Tourette syndrome, whose symptoms ameliorated dramatically in the following eight weeks.

http://ift.tt/2BXk6m6

Immediate Reconstruction and Dental Rehabilitation of Maxillofacial Defects

Condition:   Maxillofacial Injuries
Interventions:   Device: NobelActive;   Device: KLS Martin Mandibular Reconstruction Implant
Sponsors:   University of Florida;   Osteo Science Foundation
Not yet recruiting

http://ift.tt/2BWncqv

Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

Conditions:   Squamous Cell Carcinoma of the Oropharynx;   Squamous Cell Carcinoma of the Larynx;   Squamous Cell Carcinoma of the Oral Cavity;   Squamous Cell Carcinoma of the Hypopharynx;   Squamous Cell Carcinoma of the Paranasal Sinus;   Head and Neck Squamous Cell Carcinoma;   Squamous Cell Cancer;   Head and Neck Carcinoma
Interventions:   Drug: Nivolumab;   Drug: Cetuximab
Sponsors:   H. Lee Moffitt Cancer Center and Research Institute;   James and Esther King Biomedical Research Program;   Eli Lilly and Company
Recruiting

http://ift.tt/2ANwsxL

Study of Chronic Rhinosinusitis Symptoms in Asthma Patients Undergoing Treatment With Reslizumab

Conditions:   Chronic Rhinosinusitis (Diagnosis);   Asthma;   Nasal Polyps
Intervention:   Drug: Reslizumab
Sponsor:   University of Rochester
Recruiting

http://ift.tt/2BWqGcg

Thyrotoxic Atrial Fibrillation: Factors Associated with Persistence and Risk of Ischemic Stroke

Background. Atrial fibrillation (AF) is one of the commonest cardiovascular manifestations of thyrotoxicosis. A significant proportion of patients have persistent AF which may have long term consequences, for example, ischemic stroke. Methods. We performed a retrospective cohort study in a regional hospital from January 2004 to June 2016 to examine the clinical characteristics and outcomes of thyrotoxic patients who presented with atrial fibrillation and to investigate possible factors associated with persistent atrial fibrillation and ischemic stoke. Results. Among 1918 patients who had a diagnosis of thyrotoxicosis, 133 (6.9%) patients presented with AF. Spontaneous sinus conversion occurred in 89 (66.9%) patients in which 85 (94%) patients developed sinus conversion before or within 6 months after having achieved euthyroidism. The remaining 44 (33.1%) had persistent AF. The rate of ischemic stroke was numerically higher among patients who had persistent AF than those with spontaneous sinus conversion (15.9% versus 10.1%; log-rank 0.442, ). Patients who sustained an ischemic stroke were older (71 ± 11 years versus 62 ± 16 years, ) and had a trend towards higher -VASc score (2.9 ± 1.7 versus 2.3 ± 1.7, ). History of smoking (adjusted odds ratio 4.9, 95% CI ,), a larger left atrial diameter (adjusted odd ratio 2.6, 95% CI ,), and a relatively lower free thyroxine level at diagnosis (adjusted odd ratio 2.1, 95% CI ,) were associated with persistence of AF on multivariate analysis. Conclusion. Persistence of thyrotoxic AF occurred in one-third of patients and spontaneous sinus conversion was unlikely after six months of euthyroidism. High rate of ischemic stroke was observed among patients with persistent thyrotoxic AF and older age. Patients with factors associated with persistent AF, especially older people, should be closely monitored beyond 6 months so that anticoagulation can be initiated in a timely manner to reduce risk of ischemic stroke.

http://ift.tt/2BW8641

The regulatory network behind MHC class I expression

Publication date: Available online 8 December 2017
Source:Molecular Immunology
Author(s): Marlieke L.M. Jongsma, Greta Guarda, Robbert M. Spaapen
The MHC class I pathway, presenting endogenously derived peptides to T lymphocytes, is hijacked in many pathological conditions. This affects MHC class I levels and peptide presentation at the cell surface leading to immune escape of cancer cells or microbes. It is therefore important to identify the molecular mechanisms behind MHC class I expression, processing and antigen presentation. The identification of NLRC5 as regulator of MHC class I transcription was a huge step forward in understanding the transcriptional mechanism involved. Nevertheless, many questions concerning MHC class I transcription are yet unsolved. Here we illuminate current knowledge on MHC class I and NLRC5 transcription, we highlight some remaining questions and discuss the use of quickly developing high-content screening tools to reveal unknowns in MHC class I transcription in the near future.



http://ift.tt/2kp0e3W

The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Lu Meng, Longyun Li, Shan Lu, Kai Li, Zhenbo Su, Yunyun Wang, Xiaodi Fan, Xuyang Li, Guoqing Zhao
The aim of present study was to evaluate the protective effects of dexmedetomidine (DEX) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and investigate its possible mechanisms mediated by HMGB1. In vivo, pulmonary pathology observation and myeloperoxidase (MPO) activity were also examined to evaluate the protective effect of DEX in the lungs. Tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF), serum and lung tissues LPS-induced rats were detected. The oxidative indices including superoxide dismutase (SOD), Malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum were also determined. Additionally, nitric oxide (NO), TNF-α, IL-6 and IL-1β, MDA, SOD and GSH-Px in the supernatants of LPS-induced BEAS-2B cells were measured. Furthermore, we detected the protein expression of high mobility group box-1 protein (HMGB1), Toll-like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), inhibitor of NF-κB (IκBα), p-IκBα, nuclear factor kappa-B (NF-κB), p-NF-κB, phosphatidylinositol 3′-kinase (PI3K), p-PI3K, protein kinase B (Akt), p-Akt, mammalian target of rapamycin (mTOR) and p-mTOR in LPS-induced ALI rats and LPS-induced BEAS-2B cells. Immunohistochemical and immunofluorescence analyses of HMGB1 in lung tissues or BEAS-2B cells were also conducted to evaluate the mechanisms of DEX. DEX effectively attenuated pulmonary pathology, and ameliorated the levels of MPO, SOD, MDA, GSH-Px, TNF-α, IL-6, IL-1β and NO in LPS-stimulated rats and BEAS-2B cells. Additionally, treatment with DEX inhibited the expression of HMGB1, TLR4, MyD88, p-IκB, p-NF-κB, p-PI3K, p-Akt and p-mTOR in vivo and in vitro. Immunohistochemical and immunofluorescence analyses also showed that DEX suppressed HMGB1 levels in lung sections and BEAS-2B cells. Treatment with glycyrrhizin, an inhibitor of HMGB1, confirmed that HMGB1 was involved in the mechanism of DEX on LPS-induced ALI. The transfection of HGMB1 siRNA also confirmed these findings in vitro. In conclusion, the present study showed that DEX exerted a protective effect on LPS-induced ALI rats likely through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways.



http://ift.tt/2jS5fCN

Expression profiles of genes involved in TLRs and NLRs signaling pathways of water buffaloes infected with Fasciola gigantica

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Fu-Kai Zhang, Jun-Ling Hou, Ai-Jiang Guo, Ai-Ling Tian, Zhao-An Sheng, Wen-Bin Zheng, Wei-Yi Huang, Hany M. Elsheikha, Xing-Quan Zhu
Infection of ruminants and humans with Fasciola gigantica is attracting increasing attention due to its economic impact and public health significance. However, little is known of innate immune responses during F. gigantica infection. Here, we investigated the expression profiles of genes involved in Toll-like receptors (TLRs) and NOD-like receptors (NLRs) signaling pathways in buffaloes infected with 500F. gigantica metacercariae. Serum, liver and peripheral blood mononuclear cell (PBMC) samples were collected from infected and control buffaloes at 3, 10, 28, and 70days post infection (dpi). Then, the levels of 12 cytokines in serum samples were evaluated by ELISA. Also, the levels of expression of 42 genes, related to TLRs and NLRs signaling, in liver and PBMCs were determined using custom RT² Profiler PCR Arrays. At 3 dpi, modest activation of TLR4 and TLR8 and the adaptor protein (TICAM1) was detected. At 10 dpi, NF-κB1 and Interferon Regulatory Factor signaling pathways were upregulated along with activation of TLR1, TLR2, TLR6, TLR10, TRAF6, IRF3, TBK1, CASP1, CD80, and IFNA1 in the liver, and inflammatory response with activated TLR4, TLR9, TICAM1, NF-κB1, NLRP3, CD86, IL-1B, IL-6, and IL-8 in PBMCs. At 28 dpi, there was increase in the levels of cytokines along with induction of NLRP1 and NLRP3 inflammasomes-dependent immune responses in the liver and PBMCs. At 70 dpi, F. gigantica activated TLRs and NLRs, and their downstream interacting molecules. The activation of TLR7/9 signaling (perhaps due to increased B-cell maturation and activation) and upregulation of NLRP3 gene were also detected. These findings indicate that F. gigantica alters the expression of TLRs and NLRs genes to evade host immune defenses. Elucidation of the roles of the downstream effectors interacting with these genes may aid in the development of new interventions to control disease caused by F. gigantica infection.



http://ift.tt/2kp0csQ

Identification and characterization of six peroxiredoxin transcripts from mud crab Scylla paramamosain: The first evidence of peroxiredoxin gene family in crustacean and their expression profiles under biotic and abiotic stresses

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Dan-Dan Tu, Yi-Lian Zhou, Wen-Bin Gu, Qi-Hui Zhu, Bin-Peng Xu, Zhong-Kai Zhou, Ze-Peng Liu, Cong Wang, Yu-Yin Chen, Miao-An Shu
The peroxiredoxins (Prxs) define a novel and evolutionarily conserved superfamily of peroxidases able to protect cells from oxidative damage by catalyzing the reduction of a wide range of cellular peroxides. Prxs have been identified in prokaryotes as well as in eukaryotes, however, the composition and number of Prxs family members vary in different species. In this study, six Prxs were firstly identified from the mud crab Scylla paramamosain by RT-PCR and RACE methods. Six SpPrxs can be subdivided into three classes: (a) three typical 2-Cys enzymes denominated as Prx1/2, 3, 4, (b) two atypical 2-Cys enzymes known as Prx5-1 and Prx5-2, and (c) a 1-Cys isoform named Prx6. The evolutionarily conserved signatures of peroxiredoxin catalytic center were identified in all six SpPrxs. Phylogenetic analysis revealed that SpPrx3, SpPrx4, SpPrx5s and SpPrx6 were clearly classified into Prx3-6 subclasses, respectively. Although SpPrx1/2 could not be grouped into any known Prx subclasses, SpPrx1/2 clustered together with other arthropods Prx1 or unclassified Prx and could be classified into the typical 2-Cys class. The comparative and evolutionary analysis of the Prx gene family in invertebrates and vertebrates were also conducted for the first time. Tissue-specific expression analysis revealed that these six SpPrxs were expressed in different transcription patterns while the highest expression levels were almost all in the hepatopancreas. Quantitative RT-PCR analysis exhibited that the gene expression profiles of six SpPrxs were distinct when crabs suffered biotic and abiotic stresses including the exposures of Vibrio alginolyticus, poly (I:C), cadmium and hypoosmotic salinity, suggesting that the SpPrxs might play different roles in response to various stresses. The recombinant proteins including the SpPrx1/2, SpPrx4, SpPrx5-1 and SpPrx6 were purified and the peroxidase activity assays indicated that all these proteins can reduce H2O2 in a typical DTT-dependent manner. To our knowledge, this is the first study about the comprehensive characterization of Prx gene family in Scylla paramamosain and even in crustaceans. These results would broaden the current knowledge of the whole Prx family as well as be helpful to understand and clarify the evolutionary pattern of Prx family in invertebrate and vertebrate taxa.



http://ift.tt/2jS5EVP

Activated human B cells stimulate COX-2 expression in follicular dendritic cell-like cells via TNF-α

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Jini Kim, Seungkoo Lee, Dooil Jeoung, Young-Myeong Kim, Jongseon Choe
In spite of the potential importance of cyclooxygenase (COX)-2 expression in the germinal center, its underlying cellular and molecular mechanisms are largely unknown. COX-2 is the key enzyme generating pleiotropic prostaglandins. Based on our previous findings, we hypothesized that lymphocytes would stimulate COX-2 expression in follicular dendritic cell (FDC) by liberating cytokines. In this study, we examined the effect of tonsillar lymphocytes on COX-2 expression in FDC-like cells by immunoblotting. B but not T cells induced COX-2 protein in a time- and dose-dependent manner. Sub-fractionation analysis of B cell subsets revealed that activated but not resting B cells were responsible for the COX-2 induction. Confocal microscopy of frozen tonsils demonstrated that FDCs indeed express COX-2 in situ, in line with the in vitro results. To identify the stimulating molecule, we added neutralizing antibodies to the coculture of FDC-like cells and B cells. COX-2 induction in FDC-like cells was markedly inhibited by TNF-α neutralizing antibody. Finally, the actual production of TNF-α by activated B cells was confirmed by an enzyme immunoassay. The current study implies an unrecognized cellular interaction between FDC and B cells leading to COX-2 expression during immune inflammatory responses.



http://ift.tt/2kq8lx6

Role of extracellular vesicles in rheumatoid arthritis

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Haitao Fu, Die Hu, Licheng Zhang, Peifu Tang
Cell-derived extracellular vesicles (EVs) are involved in the pathogenesis of rheumatoid arthritis (RA), playing important roles in antigen presentation, inflammation, angiogenesis, cell–cell signal communication, thrombosis, and articular cartilage extracellular matrix degradation. Understanding the pathogenic mechanism of RA is important for developing therapies. The pathogenic indicators of RA, such as submicron-sized EVs, represent promising biomarkers for evaluating RA activity. This review summarizes the recent advances in understanding the pathogenesis of RA, and sheds light on the pathogenic as well as anti-inflammatory or immunosuppressive roles of EVs. We suggest that EVs could be harnessed as tools for drug delivery or targets for RA therapies.



http://ift.tt/2jS5DRL

Crystal structures of murine and human Histamine-Releasing Factor (HRF/TCTP) and a model for HRF dimerisation in mast cell activation

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Katy A. Doré, Jun-ichi Kashiwakura, James M. McDonnell, Hannah J. Gould, Toshiaki Kawakami, Brian J. Sutton, Anna M. Davies
In allergic disease, mast cell activation is conventionally triggered by allergen-mediated cross-linking of receptor-bound IgE on the cell surface. In addition to its diverse range of intracellular roles in apoptosis, cell proliferation and cancer, Histamine-Releasing Factor (HRF) also activates mast cells and basophils. A subset of IgE antibodies bind HRF through their Fab regions, and two IgE binding sites on HRF have been mapped. HRF can form dimers, and a disulphide-linked dimer is critical for activity. The current model for the activity of HRF in mast cell activation involves cross-linking of receptor-bound IgE by dimeric HRF, mediated by HRF/Fab interactions. HRF crystal and solution structures have provided little insight into either the formation of disulphide-linked HRF dimers or the ability of HRF to activate mast cells. We report the first crystal structure of murine HRF (mHRF) to 4.0Å resolution, revealing a conserved fold. We also solved the structure of human HRF (hHRF) in two new crystal forms, one at the highest resolution (1.4Å) yet reported. The high resolution hHRF structure reveals a disulphide-linked dimer, in which the two molecules are closely associated, and provides a model for the role of both human and murine HRF in mast cell activation.



http://ift.tt/2jSRnIe

Characteristics of NK cells from leukemic microenvironment in MLL-AF9 induced acute myeloid leukemia

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Feifei Yang, Rong Wang, Wenli Feng, Chong Chen, Xiao Yang, Lina Wang, Yuting Hu, Qian Ren, Guoguang Zheng
NK cells are indispensable components of tissue microenvironment and play vital in both innate and adaptive immunity. The activation and function of NK cells are affected by tumor microenvironments. NK cells are also important players in leukemic microenvironment. However, their characteristics in leukemic microenvironment, including maturation status, phenotype, subpopulations and functional roles especially immunoregulatory potential, have not been well established. Here, we studied these characteristics of NK cells in MLL-AF9 induced mouse acute myeloid leukemia (AML) model. Increase of more mature NK cells were detected in the AML spleen. Splenic AML microenvironment promoted NK cell activation in early and middle stages of leukemia. Cytotoxicity molecules and cytokines were up-regulated in activated NK cells. Furthermore, NK cells from AML microenvironment regulated T cell function, not only by maintaining the activation of CD4⁺ and promoting the degranulation of cytotoxic CD8⁺ T cells but also by influencing the differentiation of CD4⁺ T cells. Moreover, two NK cell subpopulations marked by DNAM-1 (CD226) had distinct cytokine expression patterns but similar regulatory effects on T cells. Collectively, these findings highlight the significance of immunoregulatory role of NK cells, and suggest novel therapeutic potential for leukemia by manipulating NK cell immunoregulatory activity.

Graphical abstract

http://ift.tt/2kq8h0k

Molecular mechanism of LPS-induced TNF-α biosynthesis in polarized human macrophages

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Erik Schilling, Ronald Weiss, Anja Grahnert, Michael Bitar, Ulrich Sack, Sunna Hauschildt
In response to environmental stimuli such as granulocyte-macrophage or macrophage colony stimulating factor (GM-CSF/M-CSF), macrophages (MΦ) can acquire distinct functional phenotypes that control inflammatory processes on the one hand and contribute to a broad spectrum of pathologies on the other. Potential intervention strategies will require an understanding of the signalling processes that are associated with macrophage polarization.In the present study, we show that M-MΦ produce more IFN-β and IL-10 and a lot less TNF-α than do GM-MΦ in response to LPS. To define the molecular mechanisms that underlie the biosynthesis of TNF-α we carried out a detailed investigation of the LPS-induced activation of the canonical and non-canonical myeloid differentiation primary response 88 (MyD88)-dependent signal transduction pathways as well as the TIR-domain-containing adapter-inducing interferon-β (TRIF)-dependent pathway. Our results show that all three pathways are activated in both cell types and that the activation is more pronounced in M-MΦ. While IL-10 was found to interfere with TNF-α production in M-MΦ, we exclude a decisive role for IFN-β in this respect. Furthermore, we demonstrate that TNF-α mRNA is markedly destabilized in M-MΦ and that expression of the mRNA destabilizing protein tristetraprolin is greatly enhanced in these cells.Collectively, our study suggests that differential effects of LPS on TNF-α mRNA turnover and on signal transduction pathways influence the amount of TNF-α finally produced by GM-MΦ and M-MΦ.



http://ift.tt/2kp00d6

Phospholipase A1-based cross-reactivity among venoms of clinically relevant Hymenoptera from Neotropical and temperate regions

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Amilcar Perez-Riverol, Luís Gustavo Romani Fernandes, Alexis Musacchio Lasa, José Roberto Aparecido dos Santos-Pinto, Débora Moitinho Abram, Gabriel Hideki Izuka Moraes, Frederic Jabs, Michaela Miehe, Henning Seismman, Mario Sergio Palma, Ricardo de Lima Zollner, Edzard Spillner, Márcia Regina Brochetto-Braga
Molecular cross-reactivity caused by allergen homology or cross-reactive carbohydrate determinants (CCDs) is a major challenge for diagnosis and immunotherapy of insect venom allergy. Venom phospholipases A1 (PLA1s) are classical, mostly non-glycosylated wasp and ant allergens that provide diagnostic benefit for differentiation of genuine sensitizations from cross-reactivity. As CCD-free molecules, venom PLA1s are not causative for CCD-based cross-reactivity. Little is known however about the protein-based cross-reactivity of PLA1 within vespid species. Here, we address PLA1-based cross-reactivity among ten clinically relevant Hymenoptera venoms from Neotropical and temperate regions including Polybia paulista (paulistinha) venom and Vespula vulgaris (yellow jacket) venom. In order to evaluate cross-reactivity, sera of mice sensitized with recombinant PLA1 (rPoly p 1) from P. paulista wasp venom were used. Pronounced IgE and IgG based cross-reactivity was detected for wasp venoms regardless the geographical region of origin. The cross-reactivity correlated well with the identity of the primary sequence and 3-D models of PLA1 proteins. In contrast, these mice sera showed no reaction with honeybee (HBV) and fire ant venom. Furthermore, sera from patients monosensitized to HBV and fire ants did not recognize the rPoly p 1 in immunoblotting. Our findings reveal the presence of conserved epitopes in the PLA1s from several clinically relevant wasps as major cause of PLA1-based in vitro cross-reactivity. These findings emphasize the limitations but also the potential of PLA1-based HVA diagnostics.

Graphical abstract

http://ift.tt/2jSCfKZ

Asparaginase inhibits the lectin pathway of complement activation

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): M.P. Keizer, C. Aarts, A.M. Kamp, H.N. Caron, M.D. van de Wetering, D. Wouters, T.W. Kuijpers
Oncological treatment has been associated with an increased risk of infection, most often related to therapy-induced pancytopenia. However, limited research has been conducted on the effect of oncological therapy on the complement system, being part of the non-cellular innate immune system. This became the rationale for an observational clinical study (C2012) in which we have investigated the prevalence of transient complement defects. Once we had observed such defects, a correlation of the complement defects to specific clinical parameters or to specific therapeutic regimens was investigated. A prominent defect observed in C2012 was the inhibition of the lectin pathway (LP) of complement activation during the treatment of acute lymphoblastic leukemia (ALL), which we could directly associate to the use of asparaginase (ASNase). Ex-vivo experiments confirmed a direct dose-dependent inhibitory effect of ASNase on the LP functionality.



http://ift.tt/2jRYPDz

DNA/RNA hybrid substrates modulate the catalytic activity of purified AID

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Hala S. Abdouni, Justin J. King, Atefeh Ghorbani, Heather Fifield, Lesley Berghuis, Mani Larijani
Activation–induced cytidine deaminase (AID) converts cytidine to uridine at Immunoglobulin (Ig) loci, initiating somatic hypermutation and class switching of antibodies. In vitro, AID acts on single stranded DNA (ssDNA), but neither double-stranded DNA (dsDNA) oligonucleotides nor RNA, and it is believed that transcription is the in vivo generator of ssDNA targeted by AID. It is also known that the Ig loci, particularly the switch (S) regions targeted by AID are rich in transcription-generated DNA/RNA hybrids. Here, we examined the binding and catalytic behavior of purified AID on DNA/RNA hybrid substrates bearing either random sequences or GC-rich sequences simulating Ig S regions. If substrates were made up of a random sequence, AID preferred substrates composed entirely of DNA over DNA/RNA hybrids. In contrast, if substrates were composed of S region sequences, AID preferred to mutate DNA/RNA hybrids over substrates composed entirely of DNA. Accordingly, AID exhibited a significantly higher affinity for binding DNA/RNA hybrid substrates composed specifically of S region sequences, than any other substrates composed of DNA. Thus, in the absence of any other cellular processes or factors, AID itself favors binding and mutating DNA/RNA hybrids composed of S region sequences. AID:DNA/RNA complex formation and supporting mutational analyses suggest that recognition of DNA/RNA hybrids is an inherent structural property of AID.



http://ift.tt/2koAKUi

Natural killer cells and anti-tumor immunity

Publication date: Available online 9 December 2017
Source:Molecular Immunology
Author(s): Sandra E. Nicholson, Narelle Keating, Gabrielle T. Belz
Immune checkpoint inhibitors harness the power of the immune system to fight cancer. The clinical success achieved with antibodies against the inhibitory T cell receptors PD-1 and CTLA4 has focused attention on the possibility of manipulating other immune cells, in particular those involved in innate immunity. Here we review the role of innate lymphoid cells (ILCs) and their contribution to tumor immunity. As the prototypical ILC, the natural killer (NK) cell has an intrinsic ability to detect and kill cancer cells. NK cells are dependent on the cytokine interleukin (IL)-15 for their development and effector activity. We discuss the role of the Suppressor of cytokine (SOCS) proteins in negatively regulating IL-15 and NK cell responses and the potential for targeting these small intracellular regulators as new immune checkpoints.



http://ift.tt/2jRYIb7

Silencing of H19 inhibits the adipogenesis and inflammation response in ox-LDL-treated Raw264.7 cells by up-regulating miR-130b

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Yong Han, Jie Ma, Junping Wang, Liping Wang
Atherosclerosis (AS) is the main cause of cardiovascular diseases (CADs). Lipid accumulation and inflammatory response in macrophages are two key factors in the pathogenesis of AS. In this study, we aimed to explore the regulating role of long non-coding RNA (LncRNA)-H19 in oxygenized low density lipoprotein (ox-LDL)-treated Raw264.7 cells. Compared with the healthy control, a relatively higher level of H19 was detected in the blood samples from AS patients. Obviously up-regulated expression of TG (triglycerides)/TC (total cholesterol)/LDL-C (low density lipoprotein-cholesterol) and down-regulated level of HDL-C (high density lipoprotein-cholesterol) were detected in ox-LDL-treated Raw264.7 cells. Besides that, increased expression of H19 was detected in ox-LDL-treated Raw264.7 cells. To examine the function of H19, gene knockdown was performed using short hairpin RNAs (shRNAs). The expression of TG, TC, LDL-C and HDL-C was detected by enzyme linked immunosorbent assay (Elisa) and the expression of lipolytic genes/lipogenic genes (PPARα, CPT-1/REBP-1c, ACS) was examined through western blot. In combination with the result of oil red O staining, we concluded that H19 shRNA effectively decreased lipid accumulation in ox-LDL-treated Raw264.7 cells. Besides that, H19 shRNA decreased the level of pro-inflammatory factors (TNF-α, IL-1β)/CD68+ cells and increased the level of anti-inflammatory factors (IL-4, IL-10)/CD163+ cells compared with the control group. Combined the bioinformatics analyses/luciferase assay with the promoting effect of H19 shRNA on the expression of miR-130b, we speculated that miR-130b was a target of H19 in ox-LDL-treated Raw264.7 cells. Moreover, the adding of LncRNA H19 abolished the facilitating effect of miR-130b inhibitor on adipogenesis and inflammation response by up-regulating the expression of miR-130b. Taken together, our research indicated a H19-miR130b pathway in regulating lipid metabolism and inflammation response in ox-LDL-treated Raw264.7 cells, providing new targets for AS treatment.



http://ift.tt/2koDDEP

The 20S immunoproteasome and constitutive proteasome bind with the same affinity to PA28αβ and equally degrade FAT10

Publication date: Available online 6 December 2017
Source:Molecular Immunology
Author(s): Gunter Schmidtke, Richard Schregle, Gerardo Alvarez, Eva M. Huber, Marcus Groettrup
The 20S immunoproteasome (IP) is an interferon(IFN)-γ − and tumor necrosis factor (TNF) −inducible variant of the 20S constitutive proteasome (CP) in which all its peptidolytically active subunits β1, β2, and β5 are replaced by their cytokine inducible homologues β1i (LMP2), β2i (MECL-1), and β5i (LMP7). These subunit replacements alter the cleavage specificity of the proteasome and the spectrum of proteasome-generated peptide ligands of MHC class I molecules. In addition to antigen processing, the IP has recently been shown to serve unique functions in the generation of pro-inflammatory T helper cell subtypes and cytokines as well as in the pathogenesis of autoimmune diseases, but the mechanistic involvement of the IP in these processes has remained elusive. In this study we investigated whether the IP differs from the CP in the interaction with two IFN-γ/TNF inducible factors: the 11S proteasome regulator PA28αβ and the ubiquitin-like modifier FAT10 (ubiquitin D). Using thermophoresis, we determined the affinity of PA28αβ for the CP and IP to be 12.2nM +/− 2.8nM and 15.3nM +/− 2.7nM, respectively, which is virtually identical. Also the activation of the peptidolytic activities of the IP and CP by PA28αβ did not differ. For FAT10 we determined the degradation kinetics in cycloheximide chase experiments in cells expressing almost exclusively IP or CP as well as in IFN-γ stimulated and unstimulated cells and found no differences between the degradation rates. Taken together, we conclude that neither differences in the binding strength to, nor activation by PA28αβ, nor a difference in the rate of FAT10-mediated degradation can account for distinct functional capabilities of the IP as compared to the CP.

Graphical abstract

http://ift.tt/2jQ49HA

Linking T cell epitopes to a common linear B cell epitope: A targeting and adjuvant strategy to improve T cell responses

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Sara M. Mangsbo, Erika A.K. Fletcher, Wendy W.C. van Maren, Anke Redeker, Robert A. Cordfunke, Inken Dillmann, Jasper Dinkelaar, Kahina Ouchaou, Jeroen D.C. Codee, Gijs A. van der Marel, Peter Hoogerhout, Cornelis J.M. Melief, Ferry Ossendorp, Jan W. Drijfhout
Immune complexes are potent mediators of cellular immunity and have been extensively studied for their disease mediating properties in humans and for their role in anti-cancer immunity. However, a viable approach to use antibody-complexed antigen as vehicle for specific immunotherapy has not yet reached clinical use. Since virtually all people have endogenous antibodies against tetanus toxoid (TTd), such commonly occurring antibodies are promising candidates to utilize for immune modulation. As an initial proof-of-concept we investigated if anti-tetanus IgG could induce potent cross-presentation of a conjugate with SIINFEKL, a MHC class I presented epitope of ovalbumin (OVA), to TTd. This protein conjugate enhanced OVA-specific CD8+ T cell responses when administrated to seropositive mice. Since TTd is poorly defined, we next investigated whether a synthetic peptide–peptide conjugate, with a chemically defined linear B cell epitope of tetanus toxin (TTx) origin, could improve cellular immune responses. Herein we identify one linear B cell epitope, here after named MTTE thru a screening of overlapping peptides from the alpha and beta region of TTx, and by assessment of the binding of pooled IgG, or individual human IgG from high-titer TTd vaccinated donors, to these peptides. Subsequently, we developed a chemical protocol to synthesize defined conjugates containing multiple copies of MTTE covalently attached to one or more T cell epitopes of choice. To demonstrate the potential of the above approach we showed that immune complexes of anti-MTTE antibodies with MTTE-containing conjugates are able to induce DC and T cell activation using model antigens.



http://ift.tt/2jRYAZb

Rational selection of immunodominant and preserved epitope Sm043300e from Schistosoma mansoni and design of a chimeric molecule for biotechnological purposes

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Cláudia de Souza, Marcelo Donizete Lopes, Flávio Martins De Oliveira, Maria Juliana Ferreira Passos, Laís Cunha Grossi Ferreira, Bruna Franciele Faria, José Augusto Ferreira Perez Villar, Moacyr Comar Junior, Alex Guterres Taranto, Luciana Lara dos Santos, Cristina Toscano Fonseca, Débora de Oliveira Lopes
Human schistosomiasis is a neglected tropical disease of great importance in public health. A large number of people are infected with schistosomiasis, making vaccine development and effective diagnosis important control strategies. A rational epitope prediction workflow using Schistosoma mansoni hypothetical proteins was previously presented by our group, and an improvement to that approach is presented here. Briefly, immunodominant epitopes from parasite membrane proteins were predicted by reverse vaccinology strategy with additional in silico analysis. Furthermore, epitope recognition was evaluated using sera of individuals infected with S. mansoni. The epitope that stood out in both in silico and in vitro assays was used to compose a rational chimeric molecule to improve immune response activation. Out of 2185 transmembrane proteins, four epitopes with high binding affinities for human and mouse MHCII molecules were selected through computational screening. These epitopes were synthesized to evaluate their ability to induce TCD4+ lymphocyte proliferation in mice. Sm204830e and Sm043300e induced significant TCD4+ proliferation. Both epitopes were submitted to enzyme-linked immunosorbent assay to evaluate their recognition by IgG antibodies from the sera of infected individuals, and epitope Sm043300 was significantly recognized in most sera samples. Epitope Sm043300 also showed good affinity for human MHCII molecules in molecular docking, and its sequence is curiously highly conserved in four S. mansoni proteins, all of which are described as G-protein-coupled receptors. In addition, we have demonstrated the feasibility of incorporating this epitope, which showed low similarity to human sequences, into a chimeric molecule. The stability of the molecule was evaluated by molecular modeling aimed at future molecule production for use in diagnosis and vaccination trials.



http://ift.tt/2kp9nJL

Reduced PTEN involved in primary immune thrombocytopenia via contributing to B cell hyper-responsiveness

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Shixuan Wang, Yue Guan, Yunlong Wang, Huiyuan Li, Donglei Zhang, Mankai Ju, Yating Hao, Xuewen Song, Boyang Sun, Xueqing Dou, Renchi Yang
Phosphatase and tensin homolog (PTEN) is thought to mediate B cell activation by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. This pathway is important for activation, growth, and proliferation. Although enhanced B cell receptor (BCR) signaling contributes to increased B cell activity in immune thrombocytopenia (ITP), the role of PTEN is unclear. In this study, we analyzed B cells of ITP patients using flow cytometry and found that all B cell subsets, excluding memory B cells, showed lower PTEN expression than cells from healthy controls (HCs). PTEN expression was also positively-correlated with blood platelet count, although levels were lower in patients who were platelet autoantibody-positive compared with those who were negative. We next evaluated the effects of IL-21, anti-IgM, and CD40L on PTEN expression, demonstrating that they were potent inducers of PTEN expression in normal B cells. Induction of PTEN expression was lower in B cells of ITP patients. We also found that IL-21 increased the proportion of plasma cells in peripheral blood mononuclear cells (PBMCs) of ITP patients, independent of BCR signaling. This effect was reproducible using PTEN inhibitors with cells from HCs. In summary, defective PTEN expression, regulation, and function all contribute to the B cell hyper-responsiveness that associates with ITP.



http://ift.tt/2jRYuRj

Discovery of microRNAs associated with the antiviral immune response of Atlantic cod macrophages

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Khalil Eslamloo, Sabrina M. Inkpen, Matthew L. Rise, Rune Andreassen
MicroRNAs (miRNAs) are known to play important immunoregulatory roles in teleosts, although miRNAs involved in the antiviral immune response of Atlantic cod (Gadus morhua) were previously uncharacterised. Using deep sequencing and qPCR, the present study was conducted to identify miRNAs responsive to the viral mimic, polyriboinosinic polyribocytidylic acid (pIC) in Atlantic cod macrophages. Macrophage samples isolated from Atlantic cod (n=3) and treated with pIC or phosphate buffered saline (PBS control) for 24 and 72h were used for miRNA profiling. Following deep sequencing, DESeq2 analyses identified four (miR-731-3p, miR-125b-3-3p, miR-150-3p and miR-462-3p) and two (miR-2188-3p and miR-462-3p) significantly differentially expressed miRNAs at 24 and 72h post-stimulation (HPS), respectively. Sequencing-identified miRNAs were subjected to qPCR validation using a larger number of biological replicates (n=6) exposed to pIC or PBS over time (i.e. 12, 24, 48 and 72 HPS). As in sequencing, miR-731-3p, miR-462-3p and miR-2188-3p showed significant up-regulation by pIC. The sequencing results were not qPCR-validated for miR-125b-3-3p and miR-150-3p as up- and down-regulated miRNAs at 24 HPS, respectively; however, qPCR results showed significant up-regulation in response to pIC stimulation at later time points (i.e. 48 and/or 72 HPS). We also used qPCR to assess the expression of other miRNAs that were previously shown as immune responsive in other vertebrates. qPCR results at 48 and/or 72 HPS revealed that miR-128-3-5p, miR-214-1-5p and miR-451-3p were induced by pIC, whereas miR-30b-3p and miR-199-1-3p expression were repressed in response to pIC. The present study identified ten pIC-stimulated miRNAs, suggesting them as important in antiviral immune responses of Atlantic cod macrophages. Some pIC-responsive miRNAs identified in this study were predicted to target putative immune-related genes of Atlantic cod (e.g. miR-30b-3p targeting herc4), although the regulatory functions of these miRNAs need to be validated by future studies.



http://ift.tt/2kp9ipr

IL-17 is a protection effector against the adherent-invasive Escherichia coli in murine colitis

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Hai-jia Zhang, Bin Xu, Hu Wang, Bing Xu, Guo-dong Wang, Ming-zuo Jiang, Chao Lei, Mei-ling Ding, Peng-fei Yu, Yong-zhan Nie, Kai-chun Wu, Su-mei Sha, Meng-bin Li
Inflammatory bowel disease (IBD) is caused by aberrant immune responses to the gut microbiota. Among the gut microbiota, adherent-invasive Escherichia Coli (AIEC) is thought to be the pathogen through invading the intestinal epithelial cells and causing inflammation. IL-17 secretion increase, induced by enhanced bacterial adhesion to the intestine epithelium, could on one hand protect the mucosa, but on the other hand, over amount of IL-17 initializes inflammation reactions that in turn damages the mucosa. The relationship between IL-17 and AIEC is still unclear. In this study, we tried to elucidate the function of IL-17 in AIEC-mediated colitis. Wild type (WT) and IL-17 knockout (IL-17 KO) mice were inoculated with AIEC strain E. coli LF82 and treated with dextran sodium sulphate (DSS). Histological examination of the colon was performed. Mucosa damage was assessed and scored. IL-22 and IL-17 in colon tissues were detected by ELISA, qPCR and immunohistochemistry methods. Transient AIEC colonization in IL-17 KO mice resulted in increased intestinal epithelial damage, systemic bacterial burden and mortality compared with WT controls. Moreover, IL-17 is required for the induction of IL-22 in the experimental animal models during AIEC strain E. coli LF82 colonization. These results indicate IL-17 plays a protective role in AIEC strain E. coli LF82 induced colitis by promoting IL-22 secretion.



http://ift.tt/2jRYqkx

The science behind skin care: Cleansers

Summary

Two of the most important skin care categories with profound dermatologic implications are cleansers and moisturizers. Cleansers are composed of alkaline soaps or the less barrier-damaging synthetic detergents, known as syndets. The lower skin irritation and dryness found with syndets are related to their reduced tendency to cause protein denaturation due to the charge density of protein-bound micelle-like surfactant aggregates. Many cleansing formulations are available for purchase to meet hygiene needs varying by sex, age, ethnicity, occupation, environment, personal preferences, and the presence or absence of skin disease. This discussion covers the science of skin cleansing.

http://ift.tt/2C5gsHv

Management of Intractable Nasal Hyperreactivity by Selective Resection of Posterior Nasal Nerve Branches

The posterior nasal nerves emerge from the sphenopalatine foramen and contain sensory and autonomic nerve components. Posterior nasal neurectomy is an effective method to remove pathological neural networks surrounding the inferior turbinate that cause unregulated nasal hypersensitivity with excess secretion in patients with severe allergic rhinitis (AR). We describe the sophisticated endoscopic surgical procedure that allows feasible access to the confined area and selective resection of the nerve branches with the preservation of the sphenopalatine artery (SPA). We retrospectively analyzed the cases of 23 symptomatic severe AR patients who failed to respond to standard medical treatment and underwent surgery. There have been no major complications after surgery including nasal bleeding or transient numbness of the upper teeth. The mean total nasal symptom scores (TNSS) were decreased by 70.2% at 12 months after the procedure. Our comparison of the clinical effectiveness based on the number of severed nerve branches revealed that the improvement of the TNSS was significantly higher in patients with >2 branches. We conclude that this minimally invasive technique that preserves the SPA is clinically useful and decreases the rate of postoperative complications. This trial is registered with UMIN000029025.

http://ift.tt/2AvdZsR

Overexpression of S100A7 protein is an integral part of abnormal epidermal differentiation in cornoid lamella of porokeratosis

http://ift.tt/2yhOhC9

Female pattern hair loss: a pilot study investigating combination therapy with low-dose oral minoxidil and spironolactone

Abstract

Background

Minoxidil and spironolactone are oral antihypertensives known to stimulate hair growth.

Objective

To report on a case series of women with pattern hair loss (PHL) treated with once daily minoxidil 0.25 mg and spironolactone 25 mg.

Methods

Women newly diagnosed with a Sinclair stage 2–5 PHL were scored for hair shedding and hair density before and after 12 months of treatment with oral minoxidil 0.25 mg and spironolactone 25 mg.

Results

A total of 100 women were included in this observational pilot study. Mean age was 48.44 years (range 18–80). Mean hair loss severity at baseline was Sinclair 2.79 (range 2–5). Mean hair shedding score at baseline was 4.82. Mean duration of diagnosis was 6.5 years (range 0.5–30). Mean reduction in hair loss severity score was 0.85 at 6 months and 1.3 at 12 months. Mean reduction in hair shedding score was 2.3 at 6 months and 2.6 at 12 months. Mean change in blood pressure was −4.52 mmHg systolic and −6.48 mmHg diastolic. Side effects were seen in eight women but were generally mild. No patients developed hyperkalemia or any other blood test abnormality. Six of these women continued treatment, and two women who developed urticaria discontinued treatment.

Limitations

Prospective, uncontrolled, open-label observational study.

Discussion

Once daily capsules containing minoxidil 0.25 mg and spironolactone 25 mg appear to be safe and effective in the treatment of FPHL. Placebo-controlled studies to investigate this further are warranted.

http://ift.tt/2ygZLFU

SLURP-1 is mutated in Mal de Meleda, a potential molecular signature for melanoma and a putative squamous lineage tumor suppressor gene

Abstract

Background

Mal de Meleda (MDM) is a rare inherited autosomal recessive genodermatosis characterized by palmoplantar keratoderma (PPK) with transgrediens and caused by mutations in the SLURP1 gene. Uncommonly, cutaneous tumors have been found at PPK sites in MDM patients.

Objective

To study a Middle Eastern family with MDM with both PPK and skin tumors.

Methods

We studied a Middle Eastern (Palestinian) family with clinical features of MDM and cutaneous tumors. Histopathological analysis was performed on biopsies from skin lesions found in the affected individuals. Direct sequencing of SLURP1 was performed in MDM affected members. In silico analysis of publicly available datasets was used to survey SLURP1 mRNA levels in normal and malignant tissues. Statistical analysis was performed in the R statistical language.

Results

Affected members from the Middle Eastern family displayed severe forms of PPK consistent with MDM. Histopathological analysis of the skin lesions revealed that the examined affected members exhibited skin squamous cell carcinomas (SCCs) and melanoma. Sequence analysis revealed homozygous SLURP1 mutations (c.82delT) in the affected members. Following analysis of various publicly available expression datasets, SLURP1 mRNA levels were found to be markedly elevated in tissues of epithelial lineage, relative to tissues of other lineages, and significantly suppressed in malignant tumors of epithelial lineage relative to normal or their premalignant counterparts. There was significant decrease in SLURP-1 expression in melanomas versus melanocytic nevi as well as a highly significant decrease in SLURP-1 expression in metastatic melanomas as compared to primary melanoma.

Conclusion

Our study underscores cases of Middle Eastern MDM with SLURP1 mutations and skin malignancies at PPK sites. Our findings also highlight a plausible epithelial lineage-specific tumor suppressor role for the SLURP1 gene, as well as a role in the development and metastasis of melanoma and thus a potential molecular signature for melanoma.

http://ift.tt/2AwtqRu

A case of heroin linear track hyperpigmentation: histopathology and treatment with Q-switched Nd:YAG 1064nm laser

http://ift.tt/2yhSKEP

Two cases of human cutaneous anthrax with massive tissue damage, severe edema, and slight injury to the liver

http://ift.tt/2Awtsc4

Syphilis of the pharynx

http://ift.tt/2Aw3ghN

Population-based incidence and melanoma-specific survival of cutaneous malignant melanoma in a Colombian population 2000–2009

Abstract

Background

Demographic, clinical, and morphological characteristics of cutaneous melanoma are unknown for the Colombian population. We aim to provide these characteristics as well as population-based incidence and survival data.

Methods

All patients with an invasive cutaneous melanoma diagnosed in the period 2000–2009 registered in the population-based cancer registry of the metropolitan area of Bucaramanga were included for analysis (n = 169). Age-standardized incidence rates were calculated and melanoma-specific and overall survival estimated with follow-up until June 9, 2016, using Kaplan–Meier methodology, stratifying for gender, anatomical localization, and type of affiliation to the social security system.

Results

The age-standardized melanoma incidence rate was 1.7 per 100,000, with lower limbs being the most affected body sites (42.6% of all melanomas). A high proportion of melanomas presented on the plants or palms (16%) and under the nails (7.1%); at least 24.3% of melanomas were ulcerated, and 21.1% had a Breslow thickness more than 2 mm. Melanoma-specific 5-year survival was 79.3%, with worst survival for melanomas localized on the plants (64.6%) and subungual areas (55.6%). Affiliation to the subsidized type of affiliation to the social security system was statistically significantly (P = 0.003) associated with poorer survival (68.8%) compared to the special regimes (95.8%).

Conclusions

Melanoma is a relatively rare cancer in Colombia with mainly the acral sites, high proportion of thick and ulcerated melanomas, and relatively poor survival being distinct features, indicating the need for tailor-made primary and secondary prevention strategies. Better training of pathologists in the difficult field of melanoma would improve precision of available data.

http://ift.tt/2yhP6uE

Is Lactobacillus reuteri administration beneficial to oral candida levels?

http://ift.tt/2Av1PQv

Unusual cutaneous manifestation of dermatomyositis

http://ift.tt/2C3u3iy

Medikamentöse Therapie der Acne inversa

Zusammenfassung

Acne inversa ist eine chronisch entzündliche, destruierende Hauterkrankung, die ca. 1 % der Bevölkerung betrifft. Die Therapie der Erkrankung erfolgt personalisiert und umfasst chirurgische und konservative Maßnahmen. Antibiotika kommen topisch und systemisch zum Einsatz. Sehr effektiv ist eine Kombinationstherapie bestehend aus Clindamycin und Rifampicin über 10 bis 12 Wochen. Außerdem zeigen TNF (Tumor-Nekrose-Faktor)-α-Inhibitoren eine gute Wirksamkeit und werden empfohlen. Adalimumab ist zurzeit das einzige für die Therapie von Acne inversa zugelassene Systemtherapeutikum. Die Wirksamkeit von Retinoiden ist sehr unterschiedlich. Isotretinoin wird für die Therapie von Acne inversa nicht empfohlen, jedoch zeigt Acitretin einen besseren Effekt. Immunmodulierende Substanzen, wie z. B. Dapson, Cyclosporin A, Methotrexat, Colchicin oder Kortikosteroide können für die Therapie erwogen werden, allerdings ist die Studienlage für eine Empfehlung nicht ausreichend. Hormonpräparate können den Verlauf der Erkrankung beeinflussen. Antiseptika werden stadienunabhängig unterstützend angewendet. Patienten sollten über Triggerfaktoren der Erkrankung aufgeklärt werden.

http://ift.tt/2iWqHFO

Lichen planus pigmentosus inversus in children: Case report and updated review of the literature

Abstract

Lichen planus pigmentosus inversus (LPPI) is a rare variant of lichen planus characterized by slate grey to dark black-brown macules, papules, or patches occurring in the skin folds. We present a case of LPPI in an 11-year-old girl, the second-youngest case and only the third pediatric case. This article also reviews the differential diagnosis and treatment of LPPI.

http://ift.tt/2B8R7hM

Pernio as the presenting sign of blast crisis in acute lymphoblastic leukemia

Abstract

A previously healthy 5-year-old girl presented with acute onset of blue toes and red spots on the nose and fingers. The striking nature of these lesions, along with the finding of submandibular lymphadenopathy, prompted further evaluation. Laboratory findings were remarkable for anemia, high transaminase levels, and high blast count. Histopathologic findings were consistent with early pernio. Further examination revealed acute B-cell lymphoblastic leukemia. Treatment of the leukemia led to resolution of the pernio.

http://ift.tt/2BEML32

A case of keratosis circumscripta in a Chinese boy

Abstract

Keratosis circumscripta is a rare dermatosis occurring in children and adolescents that has been reported in the English literature only in Africans and their descendants. We report here a case of keratosis circumscripta in a 13-year-old Chinese boy who presented with pruritic follicular keratotic rashes below both knees. This case indicates that keratosis circumscripta may not occur only in individuals of African descent.

http://ift.tt/2B8QTqW

Circadian rhythm in atopic dermatitis—Pathophysiology and implications for chronotherapy

Abstract

Circadian rhythm is a biological clock that controls a wide range of physiological functions throughout the body, including various skin functions. A 24-h diurnal cycle, governed by an endogenous clock in the brain, largely controls cutaneous diurnal rhythm, which external factors, including temperature, humidity, diet, and stress, also modulate locally. Circadian rhythm influences cutaneous blood flow and properties of skin barrier function, such as transepidermal water loss and capacitance, and has important implications in atopic dermatitis (AD). This review explores how aberrations in circadian rhythm may play a role in the pathogenesis of AD and proposes implementation of chronotherapy to improve treatment outcomes in patients with AD.

http://ift.tt/2BE5uvI

Internal venous anomalies in patients with a genital venous malformation

Abstract

Background

Cutaneous venous malformation (VM) can be associated with internal vascular anomalies. Our objective was to investigate the frequency of internal vascular anomalies in patients with an isolated genital venous malformation to assess the utility of screening for internal findings.

Methods

We retrospectively reviewed our Vascular Anomalies Center database for patients with a focal genital venous malformation presenting between 1999 and 2016. Abdominal and pelvic imaging reports were reviewed for internal vascular anomalies. Endoscopy reports were also reviewed when available.

Results

A focal genital venous malformation was found in 22 patients (14 female, 8 male). Ten (45%) had a venous malformation of at least one internal structure, most commonly the pelvic floor (n = 6), colon (n = 5), urethra (n = 4), and/or bladder (n = 3). Eight experienced hematuria, hematochezia, and/or rectorrhagia secondary to their internal venous malformation. In patients with internal venous malformations, the mean age of symptom presentation was 7.3 years (range 1-22 years). Two patients had malformed inferior mesenteric and portal veins visible using ultrasonography and magnetic resonance imaging. They required surgical intervention to prevent thrombosis and decrease urogenital and gastrointestinal bleeding.

Conclusion

Nearly half of our patients with a focal genital venous malformation had internal venous anomalies. Physicians should suspect urogenital or gastrointestinal venous malformations in patients with a focal genital venous malformation, especially if they develop hematuria, hematochezia, or rectorrhagia. Significant mesenteric venous trunk anomalies can also occur. Because these require surgical intervention, early recognition is important. We recommend that all patients with a focal genital venous malformation undergo abdominal and pelvic ultrasound to evaluate for internal venous anomalies.

http://ift.tt/2B8QK6S

Characteristics of pediatric recurrent erythema multiforme

Abstract

Background

Erythema multiforme (EM) is an acute condition characterized by distinctive target lesions of the skin often accompanied by mucosal ulcers. A subset of individuals experience frequent episodes of recurrent EM, which is rare and poorly understood, especially in children.

Objective

To characterize clinical features, laboratory findings, and treatment responses of pediatric recurrent EM.

Methods

A retrospective chart review was conducted at the Children's Hospital of Wisconsin in Milwaukee, Wisconsin (2000-2015) and the Mayo Clinic in Rochester, Minnesota (1990-2015). Inclusion criterion was a diagnosis before age 18 years with recurrent EM, defined as a symmetrically distributed, fixed eruption, including target lesions, with or without mucous membrane involvement, occurring on at least three occasions. A literature review was conducted to include individuals who met the inclusion criterion.

Results

Twenty-six patients were included, of whom 16 (62%) were male. The median age of onset was 9.1 years (range 0-15.7 years). Nine patients (35%) required hospitalization. Herpes simplex virus testing was positive in 9 of 17 (65%) patients. Remission was achieved in 5 of 16 (31%) patients while taking suppressive antivirals. Eight patients received continuous anti-inflammatory treatment, two (25%) of whom experienced remission.

Conclusion

This study of pediatric recurrent EM found a greater male predominance, more hospitalizations, fewer cases caused by herpes simplex virus, and a lower response to immunosuppression in children than in the general population.

http://ift.tt/2BCU8YR