Regulation of B cell proliferation and differentiation by retinoic acid

Vitamin A protects against development of infectious diseases, and B cells are important players in this process. Keys to the protective role of retinoic acid (RA) against infections appear to be its ability to enhance antibody responses against T-cell dependent and independent type 2 antigens, as well as to locally stimulate IgA production in mucosal tissues. The elucidation of molecular mechanisms involved in RA-mediated regulation of proliferation and differentiation of B cells not only helps us to understand how RA differentially regulates subsets of B cells, but might also lead to more targeted treatment of selected immune disorders and B cell malignancies.     

Fuzzy Logic Modeling of Factors Affecting Musculoskeletal Disorders in a Steel Factory in Iran: A Cross-Sectional Study

ObjectivesThe aim of this study was to model associated factors affecting musculoskeletal disorders (MSDs), using fuzzy logic in a steel factory in Iran.MethodsA cross-sectional study was conducted on steel industry workers. A 6-part questionnaire was used, consisting of demographic characteristics, occupational stress, work–family conflict, general health, occupational postures, and Nordic Musculoskeletal Questionnaire. Pearson correlation was used for statistical analysis.ResultsThe prevalence of MSDs for 270 participants in the studied factory was 94.8%. Job stress, work–family conflict, general health, and work posture had a statistically significant relationship with MSDs (P < .05). The fuzzy model demonstrated 23.8% predictability for the actual data of the study. The defuzzification data had significant correlation with real data of MSDs.ConclusionsThe results of this study provided a new perspective about associated factors affecting MSDs and demonstrate that fuzzy logic can be used as a possible tool for evaluating MSDs.     

Minimally differentiated acute myeloid leukemia (FAB AML-M0) is associated with an adverse outcome in children: a report from the Children's Oncology Group, studies CCG-2891 and CCG-2961

To assess the impact of minimally differentiated acute myeloid leukemia (AML-M0) morphology in children, we analyzed 2 sequential Children's Cancer Group AML clinical trials. We compared presenting characteristics and outcomes of 82 CCG-2891 and CCG-2961 patients with de novo, non-Down syndrome (DS) AML-M0 with those of 1620 patients with non-M0 AML, and of 10 CCG-2891 patients with DS-associated AML-M0 with those of 179 with DS-associated non-M0 AML. Morphology and cytogenetics were centrally reviewed. The non-DS AML-M0 children had a lower white blood cell (WBC) count (P = .001) than their non-M0 counterparts and a higher incidence of chromosome 5 deletions (P = .002), nonconstitutional trisomy 21 (P = .027), and hypodiploidy (P = .002). Outcome analyses considering all children with non-DS AML demonstrated no significant differences between M0 and non-M0 patients. Analyses restricted to intensive-timing CCG-2891 and CCG-2961 demonstrated comparable complete response (CR) rates (79% and 78%) between non-DS M0 and non-M0 patients. Overall survival (OS) from diagnosis (38% +/- 14% versus 51% +/- 3%; P = .160) was not significantly different between the 2 groups. OS from end of induction (45% +/- 17% versus 63% +/- 3%; P = .038), event-free survival (EFS; 23% +/- 11% versus 41% +/- 3%; P = .018), and disease-free survival (DFS; 31% +/- 14% versus 52% +/- 3%; P = .009) were inferior in the M0 group. There was no significant outcome difference between DS-associated AML-M0 and non-M0 children. This study suggests that intensively treated non-DS-associated AML-M0 children have an inferior outcome compared with children with non-M0 AML.     

Molecular targets in acute myelogenous leukemia

Acute myeloid leukemia (AML) remains the most common form of leukemia and the most common cause of leukemia death. Although conventional chemotherapy can cure between 25 and 45% of AML patients, most patients will either die of relapse or die from the complications associated with treatment. Thus, more specific and less toxic treatments for AML patients are needed. Recently, a small molecular inhibitor (STI571 or Gleevec) that targets the BCR-ABL gene was found to have a dramatic clinical effect in patients with chronic myelogenous leukemia (CML). These results have encouraged investigators to search for additional small molecular inhibitors and other targeted therapies that may be applicable to other forms of leukemia. In this review, we examine some of the signaling pathways that are aberrantly regulated in AML, focusing on the tyrosine kinase/RAS/MAP kinase and JAK/STAT pathways. After reviewing these two pathways, we explore some of the targeted therapies directed at these pathways that are under development for AML, many of which are already in clinical trials.     

Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients

Background

Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome. For the detection of circulating cancer cells, this study applied a sensitive method that employed specific tumor markers for early detection.

Methods

A total of 80 blood samples from 40 CRC patients and 40 age-matched healthy controls were collected for the study. The circulating mRNA levels of two CRC tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using an absolute quantitative real-time PCR assay in a Stratagene Mx-3000P real-time PCR system. GAPDH was used as the endogenous control.

Results

TEM-8 and CEA were primarily detected more in the CRC patients rather than in the controls: 22/40 vs 9/40, p=0.009 and 30/40 vs 11/40, p=0.00054, respectively. In the CRC patients, the mRNA level of these markers was significantly higher in comparison to the normal controls (p=0.018 and 0.01). The overall sensitivity of this panel was 65% with a specificity of 75%. Statistical analysis for demographic variants did not reach significant values.

Conclusions

TEM-8 and CEA markers were detected more frequently and in significantly higher levels in the blood samples of patients compared with samples from age-matched healthy controls. The copy number of CEA and TEM-8 mRNA, as detected by a real-time quantitative PCR, appears to be a promising marker for evaluating the risk of tumor spread.     

From the Cover: Metabolic engineering of essential oil yield and composition in mint by altering expression of deoxyxylulose phosphate reductoisomerase and menthofuran synthase

Peppermint (Mentha x piperita L.) was independently transformed with a homologous sense version of the 1-deoxy-d-xylulose-5-phosphate reductoisomerase cDNA and with a homologous antisense version of the menthofuran synthase cDNA, both driven by the CaMV 35S promoter. Two groups of transgenic plants were regenerated in the reductoisomerase experiments, one of which remained normal in appearance and development; another was deficient in chlorophyll production and grew slowly. Transgenic plants of normal appearance and growth habit expressed the reductoisomerase transgene strongly and constitutively, as determined by RNA blot analysis and direct enzyme assay, and these plants accumulated substantially more essential oil (about 50% yield increase) without change in monoterpene composition compared with wild-type. Chlorophyll-deficient plants did not afford detectable reductoisomerase mRNA or enzyme activity and yielded less essential oil than did wild-type plants, indicating cosuppression of the reductoisomerase gene. Plants transformed with the antisense version of the menthofuran synthase cDNA were normal in appearance but produced less than half of this undesirable monoterpene oil component than did wild-type mint grown under unstressed or stressed conditions. These experiments demonstrate that essential oil quantity and quality can be regulated by metabolic engineering. Thus, alteration of the committed step of the mevalonate-independent pathway for supply of terpenoid precursors improves flux through the pathway that leads to increased monoterpene production, and antisense manipulation of a selected downstream monoterpene biosynthetic step leads to improved oil composition.     

Reliability of a patient survey assessing ＂Short Form Injury Questionnaire 7＂ in Iran

Objective: Injury is a major cause of morbidity and mortality in the world.The assessment of patterns and severity of injury in high-risk groups is crucial for planning and service development.On a lar...     

Association of Plasma Retinol Binding Protein-4 (RBP4) and Sonographic Grading of Fatty Liver in Obese Iranian Children

Background

The prevalence of obesity and its related comorbidities, such as fatty liver, in children is increasing worldwide mostly due to changes in diet and life-style. Many serological markers have been suggested for screening of fatty liver but investigations for finding more reliable factors are still in progress.

Objectives

This study aimed to investigate the correlation between the level of retinol binding protein-4 (RBP4) in the serum and sonographic grading of fatty-liver severity in obese Iranian children.

Patients and Methods

This case-control, double-blind study involved 51 obese children aged between five and 17 years as the case group. In addition, 35 healthy lean children with no liver problems were selected as the control group. Plasma RBP4 (using an ELISA), serum triglycerides (TG), low-density-lipoproteins (LDL), high-density-lipoproteins (HDL), total-cholesterol (Chol), and body mass index (BMI) were measured. Grading the severity of the fatty liver condition was done by an expert radiologist in the case group.

Results

RBP4 levels in obese children (19 482.9 ± 3 302.2 pg/ml) were higher than those found in the lean control group (14 295.68 ± 2 381.3 pg/ml) (P < 0.05). In the obese patients, RBP4 levels showed a significant correlation with the grade of fatty liver and BMI (P < 0.05).

Conclusions

It was found that the level of RBP4 had a strong correlation with the severity of fatty liver. Therefore, RBP4 may be considered as a useful, noninvasive predictive biomarker of intrahepatic lipid content in obese children prior to using radiological investigations. In particular, abdominal sonography, for the evaluation of intrahepatic lipid content in obese patients, as the sensitivity of a sonography is decreased due to the increased thickness of the abdominal wall as a result of fat deposits.