Comparison of immune modulatory properties of human multipotent mesenchymal stromal cells derived from bone marrow and placenta.

Multipotent mesenchymal stromal cells (MSC) can be isolated from many tissues, including bone marrow (BM) and placenta (PL). Human placenta can be obtained readily without invasive procedures. There may be differences, however, in differentiation capacity and immunomodulation by MSC isolated from BM or PL. The early pregnancy factor (heat shock protein 10; EPF/Hsp10) is a small protein that exhibits immunomodulatory properties. We compared BM- and PL-MSC, and assessed their efficacy for suppressing T-cell proliferation in vitro and the role of EPF/Hsp10 in this process. PL-MSC were collected from whole placenta after removal of the amniotic and chorionic membranes followed by serial enzymatic digestions. The PL-MSC were compared to BM-MSC, obtained from healthy donors. Differentiation capacity, cytokine secretion, expression and secretion of immunomodulatory molecules, immunophenotype and real time proliferation were assessed using cytokine arrays, ELISA assays, flow cytometry, immunohistochemical staining and western blotting. Whereas BM-MSC consisted of a homogeneous cell population with strong expression of mesenchymal markers, PL-MSC consisted of a mixed population of cells with variable CD73, CD90 and CD105 expression. PL-MSC exhibited a significantly greater proliferation rate than BM-MSC. The presence of both stem cells and more mature cells in the PL-MSC cultures resulted in decreased differentiation capacity and reduced efficacy of immune suppression in co-cultures with T-cells. Although robust intracellular expression of EPF/Hsp10 in both BM- and PL-MSC was observed, secretion of the protein in response to immune activating stimuli remained below detectable levels. Secretion of pro-inflammatory cytokines was significantly greater in BM-MSC than PL-MSC, whereas no difference was observed in the secretion of hematopoiesis supporting growth factors. Development of culture methods for isolation of pure populations of PL-MSC may improve the quality of the product and reproducibility of results.

Bilateral symmetrical adrenal hypermetabolism on FDG PET/CT due to Cushing syndrome in well differentiated neuroendocrine carcinoma.

The (18)F-FDG PET/CT scan has been suggested for whole-body imaging to identify ectopic adrenocorticotrophic hormone secreting tumours, but there are some challenges involved. The case of a patient is presented, who was admitted with the pre-diagnosis of ectopic ACTH syndrome. On the CT, a nodular lesion was detected in the medial segment of the right lung. The FDG uptake of the lesion seemed to be increased visually, but was not pathological quantitatively (SUVmax: 1.8) on the PET/CT. There was also diffuse increased uptake (SUVmax: 14.2) in the enlarged adrenal glands. The lesion was reported as a possible malignant lesion with low FDG affinity, such as a low grade neuroendocrine tumour, while the diffuse enlarged adrenal glands with high uptake were interpreted as diffusely hyperplasic, due to Cushing's syndrome. The patient was treated with a surgical wedge resection. The histopathological diagnosis confirmed that the tumour was a grade 1 well-differentiated neuroendocrine carcinoma.

Bardet-Biedl syndrome with vulva carcinoma presented with acute renal failure: a case report.

BACKGROUND: Bardet-Biedl syndrome is a rare disorder characterized by retinal dystrophy, obesity, kidney dysfunction, polydactyly, hypogonadism and cognitive impairment. It can be accompanied by systemic findings such as malignancy, hypertension, diabetes mellitus, constitutional and functional disorders of urogenital system and liver fibrosis. CASE REPORT: A 35-year-old woman with Bardet-Biedl syndrome was referred to our outpatient nephrology clinic with dysuria, acute renal failure, and urinary tract infection. A sized 2 x 1 cm mass between labia major and minor was noted, while CT scan showed a lesion that encompassed uterus and extended to the posterior side of the bladder in the left adnexal region and a 3 cm lesion in the liver. Excisional biopsy of the mass revealed a well-differentiated, squamous cell carcinoma. Dysuria resolved with insertion of urinary catheter after bougie dilatation and the patient was referred for radiotherapy. CONCLUSION: It should be kept in the mind that renal failure may develop due to constitutional urogenital anomalies such as vulva carcinoma. This can be an important cause of morbidity and mortality in patients with Bardet-Biedl syndrome.Hippokratia 2015; 19 (2):176-178.

Interrelationship between liver hemodynamics and tumor metabolism in liver metastases: diagnostic value of Doppler perfusion index revisited.

It should be expected that the hepatic blood flow increase in the cases with liver metastasis. We aimed to find out if there is a correlation between Doppler parameters and hepatic metabolic activity in oncology patients. 35 patients with hepatic metastases who were identified by 18F-fluorodeoxyglucose positron emission tomography scan and assessed with Doppler ultrasound were included in this prospective study. Patients with hepatic disease, cardiac dysfunction, dehydration, history of alcoholism, intake of antihypertensive or vasoactive medication were excluded. Volume flow of the proper hepatic artery and the portal vein were measured in the hepatoduodenal ligament by Doppler sonography. Doppler perfusion index (the ratio of the hepatic artery flow to the total liver blood flow) and flow volumes of 31 age matched subjects were compared. Both flow of the proper hepatic artery and portal vein were found to be significantly higher in patients with liver metastasis. The mean Doppler perfusion index value was 0.2 ± 0.13 in hepatic metastases whereas 0.13 ± 0.05 in control group. Doppler perfusion index was significantly higher in liver metastases (p=0.008). A positive correlation was found between the maximum standardized uptake value of the liver and flow volume of the proper hepatic artery (r=0.774, p=0). Blood flow of the proper hepatic artery and Doppler perfusion index correlates with hepatic standardized uptake value. Flow measurements of the liver may become an important parameter for selecting patients for further positron emission tomography scan and following-up the response after systemic and local therapeutic procedures.

Interleukin-10 and tumor necrosis factor-alpha gene polymorphisms in tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease in humans killing nearly three million people and eight million cases annually. The cytokines TNF-alpha and IL-10 have been implicated in the pathogenesis of TB. Certain single nucleotide polymorphisms within the promoter region of the IL10 and TNF genes have been associated with altered levels of circulating IL10 and TNF-alpha. We analyzed TNF-alpha (-308 G/A, -238 G/A, -376 G/A) and IL10 (-1,082 G/A, -819 C/T, -592 C/A) polymorphisms in 128 patients with TB and 80 healthy subjects using by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). A significant association was found between TB and -1,082 G allele (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41). Significant difference was observed in IL10 GCC and ACC haplotypes distribution between TB and control subjects (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41; Pc: 0.004, O.R 0.53, 95% CI 0.35-0.81). No statistically significant association was found between IL-10 -819 C/T, TNF-alpha 308 G/A, -238 G/A, -376 G/A polymorphisms, functional TNFalpha/IL-10 genotypes and TB. Our findings suggest that IL-10 1082 G/A alleles or haplotypes containing these alleles may influence the Th1/Th2 balance and hence may play a role in TB susceptibility and increase risk of developing disease. This polymorphism may be one of the many genetic factors affecting disease outcome.

NRAMP1 (SLC11A1): a plausible candidate gene for systemic sclerosis (SSc) with interstitial lung involvement.

Systemic sclerosis (SSc), also termed "scleroderma," is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Nramp 1 gene has multiple pleiotropic effects on macrophage activation pathways, including up-regulation of the chemokine/cytokine genes KC, tumor necrosis factor alpha, interleukin-1 b, inducible nitric oxide syntase, and major histocompatibility complex class II expression, as well as tumoricial activity and antimicrobial activity. All of these pleiotropic effects are important for resistance to infection, but they may also be involved in the induction and maintenance of autoimmune diseases. We analyzed four natural resistance associated macrophage protein 1 (NRAMP1) gene polymorphisms including 5' promoter (GT)n microsatellite, INT4 (469 + 14G/C), 3'UTR (1729 + 55del4), and D543N (codon 543, Asp to Asn) in 52 systemic sclerosis patients with interstitial lung involvement and 136 healthy controls. We found a significant association between INT4, (GT)n polymorphisms (p = 0.006 and 0.027, respectively), and SSc. Our findings suggest that NRAMP1 is a plausible candidate gene for SSc.

The relationship between 99Tc(m)-sestamibi uptake and ultrastructural cell types of thyroid tumours.

Although several hypotheses have been suggested regarding the accumulation of 99Tc(m)-sestamibi in tumours, the exact uptake mechanism is still a matter of discussion. We investigated ultrastructural cell type of thyroid tumours by electron microscopy (EM) and compared them with uptake of 99Tc(m)-sestamibi. Thyroid scintigraphy with 99Tc(m)-sestamibi was performed on 25 patients who displayed a cold nodule on previous pertechnetate scintigraphy. Tumour-to-thyroid (T/N) uptake ratio was measured semiquantitatively. Surgery was performed in all patients and cytological evaluations were done by EM. Histopathology revealed six papillary carcinomas, 16 follicular adenomas and three Hurthle cell tumours. Thyroid cells were classified as A and B cells using EM. The cytoplasm of an A cell has the normal amount of mitochondria, whereas cytoplasm of a B cell (mitochondria-rich oxyphilic cell) contains abundant mitochondria. The median T/N ratio on the early scan for an A-cell tumour was 1.21 (range, 0.74-3.2), late T/N ratio was 1.25 (range, 0.72-3.85). The T/N ratio for the B-cell tumours was 1.42 (range, 0.6-3.6) on the early scan and 1.18 (range, 0.64-5.58) on the late scan. There was no statistically significant difference between T/N ratios of A- and B-cell tumour groups. A significant difference was also not seen between early and late T/N ratios. According to our findings, 99Tc(m)-sestamibi accumulates in thyroid tumours with both A and B cells, therefore these results suggest that the mitochondrial content of tumours is not only responsible for sestamibi uptake and retention.

The role of single photon emission computed tomography in bone imaging.

Single photon emission computed tomography (SPECT) of the bone is the second most frequently performed SPECT examination in routine nuclear medicine practice, with cardiac SPECT being the most frequent. Compared with planar scintigraphy, SPECT increases image contrast and improves lesion detection and localization. Studies have documented the unique diagnostic information provided by SPECT, particularly for avascular necrosis of the femoral head, in patients with back pain, for the differential diagnosis between malignant and benign spinal lesions, in the detection of metastatic cancer in the spine, for the diagnosis of temporomandibular joint internal derangement, and for the evaluation of acute and chronic knee pain. Although less rigorously documented, SPECT is being increasingly used in all types of situations that demand more precise anatomic localization of abnormal tracer uptake. The effectiveness of bone SPECT increases with the selection of the proper collimator, which allows one to acquire adequate counts and minimize the patient-to-detector distance. Low-energy, ultrahigh-resolution or high-resolution collimation is preferred over all-purpose collimators. Multihead gamma cameras can increase the counts obtained or shorten acquisition time, making SPECT acquisitions more practical in busy departments and also increasing image quality compared with single-head cameras. Iterative reconstruction, with the use of ordered subsets estimation maximization, provides better quality images than classical filtered back projection algorithms. Three-dimensional image analysis often aids lesion localization.

Mechanism and potential applications of bio-ligninolytic systems in a CELSS.

A large amount of inedible plant material, generated as a result of plant growth in a Controlled Ecological Life Support System (CELSS), should be pretreated and converted into forms that can be recycled on earth as well as in space. The main portion of the inedible biomass is lignocellulosic material. Enzymatic hydrolysis of this cellulose would provide sugars for many other uses by recycling carbon, hydrogen, oxygen, and nitrogen through formation of carbon dioxide, heat, and sugars, which are potential foodstuffs. To obtain monosaccharides from cellulose, the protective effect of lignin should be removed. White-rot fungi degrade lignin more extensively and rapidly than other microorganisms. Pleurotus ostreatus degrades lignin effectively, and produces edible and flavorful mushrooms that increase the quality and nutritional value of the diet. This mushroom is also capable of metabolizing hemicellulose, thereby providing a food use of this pentose containing polysaccharide. This study presents the current knowledge of physiology and biochemistry of primary and secondary metabolisms of basidiomycetes, and degradation mechanism of lignin. A better understanding of the ligninolytic activity of white-rot fungi will impact the CELSS Program by providing insights on how edible fungi might be used to recycle the inedible portions of the crops.