Interleukin 17 regulates SHP-2 and IL-17RA/STAT-3 dependent Cyr61, IL-23 and GM-CSF expression and RANKL mediated osteoclastogenesis by fibroblast-like synoviocytes in rheumatoid arthritis

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Ramamoorthi Ganesan, Mahaboobkhan Rasool
Interleukin (IL)-17 predominately produced by the Th17 cells, plays a crucial role in the fibroblast-like synoviocytes (FLS) mediated disease process of rheumatoid arthritis (RA). IL-17 exerts its pathogenic effects in RA-FLS by IL-17/IL-17RA/STAT-3 signaling. Recent studies have shown that RA-FLS produces SHP-2, Cyr61, IL-23, GM-CSF and RANKL which results in worsening of the disease. However, whether IL-17/IL-17RA/STAT-3 signaling regulates SHP-2, Cyr61, IL-23, GM-CSF and RANKL expressions in RA-FLS remains unknown. In this study, IL-17 treatment dramatically induced the production of Cyr61, IL-23 and GM-CSF in FLS isolated from adjuvant induced arthritis (AA) rats. Conversely, IL-17 mediated production of Cyr61, IL-23 and GM-CSF was abrogated by knockdown of IL-17RA using a small interfering RNA or blockade of STAT-3 activation with S3I-201 in AA-FLS. Interestingly, IL-17 treatment noticeably increased the expression of IL-17RA and SHP-2 in AA-FLS. However, silencing of IL-17RA reversed the effect of IL-17 on the expression of IL-17RA and SHP-2 in AA-FLS. In addition, an increased number of TRAP-positive multinucleated cells were observed in a coculture system consisting of IL-17 treated AA-FLS and rat bone marrow derived monocytes/macrophages. Further, mechanistically we found that IL-17 upregulated RANKL expression in AA-FLS that was dependent on the IL-17/IL-17RA/STAT-3 signaling cascade. Knockdown of IL-17RA or inhibition of STAT-3 activation decreased the IL- 17 induced RANKL expression by AA-FLS and their osteoclastogenic potential. Taken together, our findings demonstrate that IL-17 regulates SHP-2 expression and IL-17RA/STAT-3 dependent production of Cyr61, IL-23, GM-CSF and RANKL in AA-FLS and may reveal a new insight into the pathogenesis of RA.



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The varying role of vertebrae in Pacific fishbone analysis; comparing tropical versus temperate midden assemblages

Abstract

Archaeologists working in the tropical Pacific have demonstrated the feasibility and value of including fish vertebrae in midden analyses, and recent New Zealand studies draw similar conclusions. This work provides an illustrated guide to the identification of vertebrae from key New Zealand fish taxa and shows the effects of including vertebrae on a large fishbone assemblage from southern New Zealand. We note major differences between New Zealand and tropical Pacific assemblages resulting from the inclusion of vertebrae. Unlike the Indo-Pacific taxa of the tropical Pacific, no New Zealand species have been shown to be sensitive to the inclusion of vertebrae. In both places including vertebrae results in changes in relative abundance and rank order but in New Zealand this is a function of processing practices, not fishing behaviours. This work serves to highlight changes in the Polynesian fishing adaption following the colonisation of New Zealand.

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Animal Remains from Ritual Sites: a Cautionary Tale from the Eastern Adriatic

Abstract

This article assesses the potential pitfalls of extant methods and criteria used for identifying of the ritual use and consumption of animals. Previous analysis of the Late Iron Age sanctuary assemblage from Spila Nakovana identified the ritual consumption of domestic animals in the sanctuary through comparison with a common set of criteria for the identification of ritual patterning in faunal assemblages. A recent analysis of a larger sample from Spila Nakovana has overturned this original determination, leading to a re-evaluation of the ranked importance of the common criteria utilised for ritual patterning identification. The importance of context is addressed in the determination of ritual patterning within archaeological faunal assemblages, with regard to both the direct and wider context of the sample.

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Role of imaging in the diagnosis of parotid infantile hemangiomas

Publication date: November 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 102
Author(s): Fabiola C. Weber, Arin K. Greene, Denise M. Adams, Marilyn G. Liang, Mohammed H. Alomari, Stephan D. Voss, Gulraiz Chaudry
ObjectivesTo review the clinical presentation, imaging and follow-up of parotid infantile hemangiomas (IH).MethodsOver a 15-year period, all patients with a clinical diagnosis of parotid IH were evaluated. Imaging was available in 35. The medical records, photographs, and radiology studies of these patients were reviewed.ResultsAll patients presented at less than 4 months of age (M:F, 13:21). 19 (55)% of tumors were on the left and were bilateral in 2 patients. The majority (29 patients) presented due to localized swelling or palpable mass; the remainder had a cutaneous lesion, but no palpable mass at the time of presentation. The referring diagnosis was incomplete or incorrect in 9 patients (26%).The imaging studies all demonstrated a well-defined homogeneous mass, with no abnormality of the surrounding subcutaneous fat. Sonography showed a uniformly vascular lesion with pulsatile fast-flow seen on Doppler. On MRI, the lesion was hyperintense on T2-weighted images, isointense on T1, with intense enhancement post-contrast.Oral therapy (propranolol or corticosteroids) was prescribed in 15 (45%). Follow-up in 28 patients demonstrated stability of the lesion in 11, regression in size in 11 and complete involution in 6. After involution 2 patients underwent resection of residual tissue and/or excess skin.ConclusionsTypical clinical presentation alone may be adequate to establish a diagnosis of parotid infantile hemangioma. However, in patients with no overlying cutaneous lesion, imaging can play a critical role in confirming the diagnosis. The sonographic findings are sufficiently characteristic to allow for a definitive diagnosis, obviating the need for further investigations. If diagnostic uncertainty remains or the full extent of the lesion cannot be appreciated, then MRI should be preferred over CT to avoid ionizing radiation.



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Shrinkage in oral squamous cell carcinoma: An analysis of tumor and margin measurements in vivo, post-resection, and post-formalin fixation

Publication date: Available online 12 September 2017
Source:American Journal of Otolaryngology
Author(s): Lauren A. Umstattd, Jonathan C. Mills, William A. Critchlow, Gregory J. Renner, Robert P. Zitsch
PurposeTo quantify changes in tumor size and tumor-free margins following surgical resection and formalin fixation of oral cavity squamous cell carcinoma.Materials and methodsNineteen patients were studied via cohort design. Between May and December 2011, measurements of tumor size and tumor-free margin were made in patients with squamous cell carcinoma of the oral cavity. Mucosal reference points were marked with sutures, representing tumor diameter and two separate resection margins. Measurements were recorded immediately before resection, after resection, and following fixation in formalin.ResultsThe overall mean shrinkage in tumor size was 10.7% (95% CI 3.4–18.0, p=0.006). When comparing mean tumor measurements, most of the tumor size decrease (6.4%, 95% CI 0.4–12.4, p=0.039) occurred between pre- and post-excision measurements. To a lesser extent, tumor size decreased following formalin fixation. Comparison of tumor-free margin measurements revealed a pre-excision to post-fixation mean decrease of 11.3% (95% CI 2.9–19.6%, p=0.011), with a statistically significant decrease of 14.9% (95% CI 8.5–21.3%, p<0.001) occurring between pre- and post-excision, and no significant decrease from post-excision to post-formalin fixation.ConclusionMucosal dimensions of both tumor and tumor-free margins in oral cavity squamous cell carcinoma specimens decrease between surgical resection and pathologic analysis. Most of this decrease occurs prior to fixation, especially for margins, and may be due to intrinsic tissue properties rather than formalin effects.



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Focal hyperkeratosis overlying the palmar faces of interphalangeal and metacarpophalangeal joints revealing a juvenile dermatomyositis

Abstract

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by an inflammatory infiltrate primarily affecting the skeletal muscle and skin [1]. It is the commonest of the idiopathic inflammatory myopathies of childhood, comprising 85% of cases. It has an annual incidence estimated to range between 1.9 and 4.1 per million children [2, 3].

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Clinical predictors of multiple tympanostomy tube placements in Ontario children

Objectives

To characterize risk factors that predict the need for multiple tympanostomy tube (TT) procedures.

Study Design

Retrospective population-based cohort study of children aged 18 years and younger in Ontario, Canada, who underwent at least one TT placement between January 1, 1994, and October 31, 2013.

Methods

The relative risk (RR) of need for multiple TT procedures was determined using log-binomial regression.

Results

There were 193,880 children who underwent TT insertion included in this cohort. Of these, 28.58% underwent at least two separate TT procedures. Over time, the RR of undergoing multiple TT procedures is decreasing for all children. In general, the younger the child was at the first TT procedure, the more likely the child was to undergo multiple TT procedures. Significantly higher RR for multiple TT procedures also was associated with male sex, the second-highest neighborhood income quintile, asthma or reactive airways, gastrointestinal disease, prematurity, or cleft lip and/or palate. Significantly lower RR for multiple TT procedures was associated with adenoidectomy or tonsillectomy (with or without adenoidectomy) at first TT placement or within 3 years prior. Furthermore, the benefit of adjuvant adenoidectomy or tonsillectomy was present for children aged under 4 years, in addition to those aged 4 years and older.

Conclusion

Among Ontario children who have had TT placement, more than one in four will have multiple sets placed. These identified risk factors permit improved preoperative counseling and enable identification of children who need closer follow-up.

Level of Evidence

2b. Laryngoscope, 2017

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