Immunohistochemical localization of irisin in skin,eye, and thyroid and pineal glands of the crested porcupine (Hystrix cristata)

Irisin was first identified in muscle cells. We detected irisin immunoreactivity in various organs of the crested porcupine (Hystrix cristata). In the epidermis, irisin immunoreactivity was localized mainly in stratum basale, stratum spinosum and stratum granulosum layers; immunoreactivity was not observed in the stratum corneum. In the dermis, irisin was found in the external and internal root sheath, cortex and medulla of hair follicles, and in sebaceous glands. Irisin immunoreactivity was found in the neural retina and skeletal muscle fibers associated with the eye. The pineal and thyroid glands also exhibited irisin immunoreactivity.     

Effects of discontinuation of growth hormone treatment on body composition and metabolism

This study was directed to the investigation of two different aspects of growth hormone: What are the metabolic consequences following the discontinuation of treatment and are these metabolic effects correlated with the growth-promoting effects seen in the first year of treatment? The study was performed on 12 growth hormone-deficient (GHD) patients who reached their final height. Each patient was matched with a non-GHD person of the same sex and about the same age. Immediately after the discontinuation of treatment, and 6 weeks and 6 months later, the following anthropometric variables were assessed: height, weight, skinfold thicknesses (biceps, triceps, subscapular and suprailiacal), body volume (underwater weighing) and total body water (deuterium dilution). To describe energy metabolism, basal metabolic rate assessed by ventilated hood, and sleep metabolic rate assessed by respiration chamber, were studied. Body composition was calculated from weight, volume and total body water. Clear metabolic effects were found after the discontinuation of treatment in GHD children: there was a decrease in fat free mass and sleep metabolic rate. Also, a strong correlation between the above-mentioned effects and the growth-promoting effects of human growth hormone at the beginning of the treatment was observed. The fact that this correlation exists poses the interesting question of whether the results from a test treatment lasting some weeks could be used to predict the long-term effects of hGH.     

Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats

Background

Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries. Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease. However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. The first successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.

Results

This study demonstrates that atypical scrapie has distinct clinical, pathological and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype.

Conclusions

Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage.     

Fracture prevention in COPD patients; a clinical 5-step approach

Although osteoporosis and its related fractures are common in patients with COPD, patients at high risk of fracture are poorly identified, and consequently, undertreated. Since there are no fracture prevention guidelines available that focus on COPD patients, we developed a clinical approach to improve the identification and treatment of COPD patients at high risk of fracture. We organised a round-table discussion with 8 clinical experts in the field of COPD and fracture prevention in the Netherlands in December 2013. The clinical experts presented a review of the literature on COPD, osteoporosis and fracture prevention. Based on the Dutch fracture prevention guideline, they developed a 5-step clinical approach for fracture prevention in COPD. Thereby, they took into account both classical risk factors for fracture (low body mass index, older age, personal and family history of fracture, immobility, smoking, alcohol intake, use of glucocorticoids and increased fall risk) and COPD-specific risk factors for fracture (severe airflow obstruction, pulmonary exacerbations and oxygen therapy). Severe COPD (defined as postbronchodilator FEV₁ < 50% predicted) was added as COPD-specific risk factor to the list of classical risk factors for fracture. The 5-step clinical approach starts with case finding using clinical risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and imaging of the spine), differential diagnosis, treatment and follow-up. This systematic clinical approach, which is evidence-based and easy-to-use in daily practice by pulmonologists, should contribute to optimise fracture prevention in COPD patients at high risk of fracture.     

Evidence for cadherin-11 cleavage in the synovium and partial characterization of its mechanism

IntroductionEngagement of the homotypic cell-to-cell adhesion molecule cadherin-11 on rheumatoid arthritis (RA) synovial fibroblasts with a chimeric molecule containing the cadherin-11 extracellular binding domain stimulated cytokine, chemokine, and matrix metalloproteinases (MMP) release, implicating cadherin-11 signaling in RA pathogenesis. The objective of this study was to determine if cadherin-11 extracellular domain fragments are found inside the joint and if a physiologic synovial fibroblast cleavage pathway releases those fragments.MethodsCadherin-11 cleavage fragments were detected by western blot in cell media or lysates. Cleavage was interrupted using chemical inhibitors or short-interfering RNA (siRNA) gene silencing. The amount of cadherin-11 fragments in synovial fluid was measured by western blot and ELISA.ResultsSoluble cadherin-11 extracellular fragments were detected in human synovial fluid at significantly higher levels in RA samples compared to osteoarthritis (OA) samples. A cadherin-11 N-terminal extracellular binding domain fragment was shed from synovial fibroblasts after ionomycin stimulation, followed by presenilin 1 (PSN1)-dependent regulated intramembrane proteolysis of the retained membrane-bound C-terminal fragments. In addition to ionomycin-induced calcium flux, tumor necrosis factor (TNF)-α also stimulated cleavage in both two- and three-dimensional fibroblast cultures. Although cadherin-11 extracellular domains were shed by a disintegrin and metalloproteinase (ADAM) 10 in several cell types, a novel ADAM- and metalloproteinase-independent activity mediated shedding in primary human fibroblasts.ConclusionsCadherin-11 undergoes ectodomain shedding followed by regulated intramembrane proteolysis in synovial fibroblasts, triggered by a novel sheddase that generates extracelluar cadherin-11 fragments. Cadherin-11 fragments were enriched in RA synovial fluid, suggesting they may be a marker of synovial burden and may function to modify cadherin-11 interactions between synovial fibroblasts.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0647-9) contains supplementary material, which is available to authorized users.     

An IGF-I promoter polymorphism modifies the relationships between birth weight and risk factors for cardiovascular disease and diabetes at age 36

BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging.     

Tuberculosis masquerading as malignancy: a multimodality approach to the correct diagnosis – a case report

BACKGROUND: Extrapulmonary tuberculosis is one of the great mimickers of medicine, and often masquerades as malignancy. As a result, patients may be referred to oncologists and surgeons for further evaluation and management, delaying the institution of appropriate anti-tuberculous drug therapy. CASE PRESENTATION: We present the case of a 21 year old man with tuberculous osteomyelitis, who was referred to the Bone and Soft Tissue Sarcoma Service at our institution with a provisional diagnosis of malignancy. Further investigation revealed extensive retroperitoneal abdominal and pelvic lymphadenopathy. The recognition of certain patterns on imaging, and finally the isolation of Mycobacterium tuberculosis from tissue samples obtained under image guidance, enabled the correct diagnosis to be made. CONCLUSION: This case highlights the importance of remaining cognisant of the protean manifestations of extrapulmonary tuberculosis, and illustrates the advantage of a clinically directed multi-modality imaging approach to diagnosis.     

Multidisciplinary approach to diagnosis and management of osteosarcoma – a review of the St Vincent's Hospital experience

Background

Osteosarcoma is the most common primary malignant bone tumour in children and young adults. Despite advances in the diagnosis and management of osteosarcoma, there have been few recent studies describing the experiences of tertiary referral centres. This paper aims to describe and discuss the clinical features, pre-operative work-up, management and outcomes of these patients at St Vincent's Hospital (Melbourne, Australia).

Methods

Retrospective study of fifty-nine consecutive patients managed for osteosarcoma at St Vincent's Hospital between 1995 and 2005.

Results

Median age at diagnosis was 21 (range, 11–84) years. Gender distribution was similar, with thirty-one male and twenty-eight female patients.Twenty-five patients had osteosarcoma in the femur, eleven each were located in the humerus and tibia, six were identified in the pelvis, and one each in the clavicle, maxilla, fibula, sacrum, ulna and radius.Pre-operative tissue diagnosis of osteosarcoma was obtained through computed tomography-guided percutaneous biopsy in over ninety percent of patients.Following initial therapy, over fifty percent of patients remained relapse-free during the follow-up period, with twelve percent and twenty-seven percent of patients documented as having local and distant disease recurrence, respectively. Of patients with recurrent disease, sixty-two percent remained disease-free following subsequent surgical intervention (most commonly, pulmonary metastatectomy).

Conclusion

Patient outcomes can be optimised through a multidisciplinary approach in a tertiary referral centre. At St Vincent's Hospital, survival and relapse rates of patients managed for osteosarcoma compare favourably with the published literature.