Adrian Kis

The protective role of bone morphogenetic protein-8 in the glucocorticoid-induced apoptosis on bone cells

One of the side effects associated with glucocorticoid therapy is glucocorticoid-induced bone loss. Glucocorticoids partly detain bone formation via the inhibition of osteoblastic function, however, the exact mechanism of this inhibition remains elusive. In this study, we examined the effect of dexamethasone, an active glucocorticoid analogue, on cell viability and expression of bone remodelling-related genes in primary mouse calvarial and cloned MC3T3-E1 osteoblasts. Using sensitive biochemical assays, we demonstrated the apoptotic effect of dexamethasone on osteoblastic cells. Then, utilizing Taqman probe-based quantitative RT-PCR technology, gene expression profiles of 111 bone metabolism-related genes were determined. As a result of dexamethasone treatment we have detected significant apoptotic cell death, and six genes, including Smad3, type-2 collagen α-1, type-9 collagen α-1, matrix metalloproteinase-2, bone morphogenetic protein-4 and bone morphogenetic protein-8 showed (BMP-8) significant changes in their expression on a time- and concentration-dependent manner. BMP-8, (a novel player in bone-metabolism) exhibited a two orders of magnitude elevation in its mRNA level and highly elevated protein concentration by Western blot in response to dexamethasone treatment. The knockdown of BMP-8 by RNA interference significantly increased dexamethasone-induced cell death, confirming a protective role for BMP-8 in the glucocorticoid-induced apoptosis of osteoblasts. Our results suggest that BMP-8 might be an essential player in bone metabolism, especially in response to glucocorticoids.

Sarcoidosis lymphoma syndrome - the value of PET-CT in the diagnosis

We report a 52-year-old patient who developed B-cell non-Hodgkin’s lymphoma subsequent to sarcoidosis. Sarcoidosis was diagnosed 16 years ago and remained asymptomatic for 14 years after steroid treatment. She presented with new symptoms of arthralgia, photosensitivity, butterfly erythema, autoimmune antibodies (ANA, chromatin positivity) associated with progression of the known left upper lobe lesion on the chest X-ray suggesting primary autoimmune disease (systemic lupus erythematosus). As steroid treatment was not effective, we started bolus cyclophosphamide therapy after which progression was seen on the chest X-ray. Computed tomography (CT)-guided needle biopsy confirmed malignancy of indefinable origin. Despite of the well-known fluorodeoxyglucose (FDG) avidity in active sarcoidosis, a FDG-positron emission tomography (PET) scan was performed to stage the primary tumour. Intensive FDG uptake was detected in the affected lung segment, with moderate uptake in mediastinal lymph nodes. The patient underwent left upper lobectomy. The histology showed pulmonary mucosa-associated lymphoma (bronchus-associated lymphoid tissue (BALT) lymphoma) in the lung tissue, while only sarcoidosis was present in the mediastinal lymph nodes. Bone marrow biopsy was negative.The association between sarcoidosis and lymphoma is known as sarcoidosis lymphoma syndrome, which is a rare disease. PET-CT was helpful in the differentiation of sarcoidosis and malignancy in this patient. It is important to be aware of the risk of lymphoma in sarcoidosis and FDG-PET, used for adequate purpose, can help the diagnosis.

Gene expression patterns in the bone tissue of women with fibrous dysplasia.

Fibrous dysplasia is an isolated skeletal disorder caused by a somatic activating mutation of GNAS gene with abnormal unmineralized matrix overproduction and extensive undifferentiated bone cell accumulation in the fibro‐osseous lesions. The aim of our investigation was to identify genes that are differently expressed in fibrous versus non‐fibrous human bone and to describe the relationships between these genes using multivariate data analysis. Six bone tissue samples from female patients with fibrous dysplastia (FD) and seven bone tissue samples from women without FD (non‐FD) were examined. The expression differences of selected 118 genes were analyzed by the TaqMan probe‐based quantitative real‐time RT‐PCR system. The Mann–Whitney U‐test indicated marked differences in the expression of 22 genes between FD and non‐FD individuals. Nine genes were upregulated in FD women compared to non‐FD ones and 18 genes showed a downregulated pattern. These altered genes code for minor collagen molecules, extracellular matrix digesting enzymes, transcription factors, adhesion molecules, growth factors, pro‐inflammatory cytokines, and lipid metabolism‐affected substrates. Canonical variates analysis demonstrated that FD and non‐FD bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via a G‐protein coupled pathway and BMP cascade as well as genes coding for extracellular matrix composing molecules. The remarkable changed gene expression profile observed in the fibrous dysplastic human bone tissue may provide further insight into the pathogenetic process of fibrous degeneration of bone.

Spontaneous Pneumomediastinum After Kidney Transplantation: Case Report

Spontaneous pneumomediastinum is a rare condition with nonspecific signs and symptoms. A 39-year-old underwent cadaver kidney transplantation. After an uncomplicated operation, progressive dyspnea of unknown origin developed. Findings at chest radiography suggested pneumomediastinum, which was confirmed at computed tomography. Esophageal or tracheal injury was ruled out. The rapidly developing atelectasis of the left lung necessitated urgent bronchoscopy, which revealed occlusion of the left main bronchus. After removal of the occluding mucus plug, the clinical symptoms immediately improved, and the spontaneous pneumomediastinum resolved within 3 days. Asymptomatic increase in airway secretions in patients receiving peritoneal dialysis may result in mucus plug formation during general anesthesia, which can cause spontaneous pneumomediastinum.