Antitumor Activity of miR-1280 in Melanoma by Regulation of Src

MicroRNAs (miRNAs) play a key role in cancer progression by coordinately repressing target genes involved in cell proliferation, migration, and invasion. miRNAs regulate gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report that expression of miR-1280 is significantly suppressed in human melanoma specimens when compared with nevi, and in human melanoma cell lines when compared with cultured normal human melanocytes. The proto-oncogene Src was identified as a target of miR-1280 action. Levels of Src expression were significantly higher in melanoma samples and cell lines than in nevi and normal melanocytes. miR-1280 overexpression significantly suppressed the luciferase activity of reporter plasmids containing the full-length 3′ untranslated region of Src. miR-1280-mediated suppression of Src led to substantial decreases in melanoma cell proliferation, cell cycle progression, invasion, as well as induced melanoma cell apoptosis. The effects of miR-1280 overexpression on melanoma cell proliferation and growth were reversed by Src overexpression. Intratumoral delivery of miR-1280 significantly suppressed melanoma cell growth in vivo. Our results demonstrate a novel role for miR-1280 as a tumor suppressor in melanoma, identify the Src signaling pathway as a target of miR-1280 action, and suggest a potential therapeutic role for miR-1280 in melanoma.     

Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction

We have developed a real-time quantitative polymerase chain reaction (PCR) assay using TaqMan technology (Applied Biosystems, Foster City, CA) for monitoring donor cell engraftment in allogenic hematopoietic stem cell transplant recipients. For this purpose, we selected 19 specific sequence polymorphisms belonging to 11 human biallelic loci located on 9 different chromosomes. Using a set of specially designed primers and fluorogenic probes, we evaluated the 19 markers' informativity on a panel of 126 DNA samples from 63 recipient/donor pairs. In more than 90% of these pairs, discrimination between recipient and donor genetic profile was possible. By using serial dilutions of mixed DNAs, we evaluated the linearity and sensitivity of the method. A linear correlation with r higher than 0.98 and a sensitivity of 0.1% proved reproducible. Fluorescent-based PCR of short tandem repeats (STR-PCR) and real-time PCR chimerism assay were compared with a panel of artificial cell mixtures. The main advantage of the real-time PCR method over STR-PCR chimerism assays is the absence of PCR competition and plateau biases, and results evidenced greater sensitivity and linearity with the real-time PCR method. Furthermore, different samples can be tested in the same PCR run with a final result in fewer than 48 hours. Finally, we prospectively analyzed patients who received allografts and present 4 different clinical situations that illustrate the informativity level of our method. In conclusion, this new assay provides an accurate quantitative assessment of mixed chimerism that can be useful in guiding early implementation of additional treatments in hematopoietic stem cell transplantation.     

Monozygotic twins concordant for narcolepsy-cataplexy without any detectable abnormality in the hypocretin (orexin) pathway

Narcolepsy with cataplexy is thought to be a hypocretin ligand or hypocretin receptor deficiency syndrome caused by genetic and environmental factors. We looked for an abnormality of the hypocretin pathway in HLA-DQB1*0602-positive monozygotic twins who were concordant for narcolepsy-cataplexy. They had normal cerebrospinal fluid concentrations of hypocretin-1, and we found no mutation in the prepro-hypocretin gene or either hypocretin receptor gene. Our finding points to the existence of presumably genetic forms of narcolepsy with cataplexy without any demonstrable defect in the hypocretin pathway.     

Dynamics of Red Cell Egress from Bone Marrow after Blood Letting

S ummary . To study the dynamics of red cell egress from the marrow, the demand for red cell delivery was enhanced in splenectomized rats by removing 25% of the blood volume, which was then immediately replaced by plasma. Within 15 min, packed cell volume declined by 22% of the initial value. Corrected reticulocyte count followed a biphasic pattern: an initial peak amounting to 26% occurred within 4-6 h followed by a more marked peak after 48 h. Quantitative electron microscopy of the marrow sinus wall indicated significant increases in the numbers of reticulocytes and leucocytes in transit after 5 h. Vesicles containing a flocculant substance were seen in the endothelium. The vesicles could cause segmental destabilization of endothelium, providing suitable areas for cell migration. There was also a significant reduction in the mean length of the overlapping segments of the endothelial cells, suggesting that these cells slid over one another to increase the luminal calibre. Within the rigid confines of bones where the marrow volume is fixed, this increase may lead to the displacement of mature haemopoietic cells into the lumen and whence into the circulation.     

An Unusual Case of Hematochezia: Acute Ischemic Proctosigmoiditis

Acute ischemia of the rectum is uncommon and usually occurs after aorto-iliac surgery. In this report, we present a case of acute ischemic proctosigmoiditis that developed from a brief episode of hypotension. An 85-year-old male presented to the emergency room with hypotension, mental confusion, and passage of maroon-colored stool. He was resuscitated and treated for presumed sepsis. Computerized tomography of the abdomen and pelvis displayed signs of acute inflammation of the distal colon and rectum. Endoscopic findings and microscopic examination of the rectal biopsy revealed changes consistent with acute ischemic proctosigmoiditis. An evaluation for infectious etiologies was negative. The patient's clinical condition improved over the next 24 h with supportive care. Involvement of the rectum is rare in ischemic colitis because of its abundant collateral blood supply. Acute ischemic proctosigmoiditis should be considered in the differential diagnosis of elderly patients with multiple co-morbidities presenting with hematochezia.     

Blood sugar changes and hospital mortality in multiple trauma

Objectives

Hyperglycemia with unknown mechanism plays a predictive role in determining the prognosis of multiple trauma patients. The exact time of blood sugar measurement and the role of blood sugar changes in the monitoring of these patients have not been well established.

Structural and impedance spectroscopy characteristics of BaCO3/BaSnO3/SnO2 nanocomposite: observation of a non-monotonic relaxation behavior

A BaCO₃/BaSnO₃/SnO₂ nanocomposite has been prepared using a co-precipitation method without adding any additives. The prepared sample was characterized by using X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectroscopy, energy dispersive X-ray spectroscopy (EDS) and Raman spectroscopy. Detailed studies on the dielectric and electrical behavior (dielectric constant, complex impedance Z*, ac conductivity, and relaxation mechanisms) of the nanocomposite have been performed using the nondestructive complex impedance spectroscopy technique within the temperature range 150–400 K. The dielectric constant of the sample as a function of temperature showed the typical characteristics of a relaxor. The maximum dielectric constant value was observed to depend on frequency. The non-monotonic relaxation behavior of the prepared nanocomposite was evidenced from the spectra of loss tan, tan(δ). The relaxation kinetics was modeled using a non-Arrhenius model.

A BaCO₃/BaSnO₃/SnO₂ nanocomposite has been prepared using a co-precipitation method without adding any additives.     

Work-related accidents among the Iranian population: a time series analysis, 2000–2011

Background

Work-related accidents result in human suffering and economic losses and are considered as a major health problem worldwide, especially in the economically developing world.

Objectives

To introduce seasonal autoregressive moving average (ARIMA) models for time series analysis of work-related accident data for workers insured by the Iranian Social Security Organization (ISSO) between 2000 and 2011.

Methods

In this retrospective study, all insured people experiencing at least one work-related accident during a 10-year period were included in the analyses. We used Box–Jenkins modeling to develop a time series model of the total number of accidents.

Results

There was an average of 1476 accidents per month (1476·05±458·77, mean±SD). The final ARIMA (p,d,q) (P,D,Q)_s model for fitting to data was: ARIMA(1,1,1)×(0,1,1)₁₂ consisting of the first ordering of the autoregressive, moving average and seasonal moving average parameters with 20·942 mean absolute percentage error (MAPE).

Conclusions

The final model showed that time series analysis of ARIMA models was useful for forecasting the number of work-related accidents in Iran. In addition, the forecasted number of work-related accidents for 2011 explained the stability of occurrence of these accidents in recent years, indicating a need for preventive occupational health and safety policies such as safety inspection.     

Modification on Direct Agglutination Antigen Preparation for Simplified Sero-Diagnosis of Human and Canine Visceral Leishmaniasis

Background: Visceral leishmaniasis is systematic serous parasitic disease with public health importance. Zoonotic form of visceral leishmaniasis is wide spread in Mediterranean basin and South America regions. Direct agglutination test (DAT) is an accurate, reliable and non-expensive serological test for the diagnosis of visceral leishmaniasis in human and canines but the antigen preparation involves some limitations. This study aimed to compare the conventional production of DAT antigen with our modified DAT antigen and then assessed on human and dog pooled sera. Methods: Conventional DAT antigen has been prepared at the School of Public Health, Tehran University of Medical Sciences and some modifications were carried out on it, which named as modified DAT antigen. Three positive and one negative human and dog pooled serum were separately used for the comparison of modified DAT with conventional DAT antigen batches with one-month interval for a period of 9 months. Results: A good concordance was observed between modified DAT compared to conventional DAT antigens for the detection of visceral leishmaniasis on human (100%) and dog (94.4%) pooled sera, respectively. Conclusion: Since the modified DAT antigen could be reduced the preparation time from 3 days to several hours and a good degree of agreement was found between modified DAT and convention DAT antigen batches, it can be used as a simple and easy tool for screening and serodiagnosis of human and canine L. infantum infection.Key Words: Direct agglutination test, Antigen modification, Visceral leishmaniasis