Evaluation of epidemiological and clinical factors in survival of patients with de novo myelodysplastic syndrome at the University of Texas MD Anderson cancer center

Little is known about epidemiological markers that are associated with survival of patients with myelodysplastic syndromes (MDS). We conducted a secondary case-based analysis of 465 de novo MDS patients from the University of Texas MD Anderson Cancer Center (UTMDACC). We investigated the association between demographic as well as occupational exposure markers and survival while incorporating known clinical markers of prognosis. In our patient population, 60.6% were men and the majority were white (93.1%). The distribution of MDS subtypes by the French–American–British (FAB) classification was 81 (19%) refractory anemia (RA), 46 (9.9%) refractory anemia with ringed sideroblasts (RARS), 57 (12.3%) chronic myelomonocytic leukemia (CMML), 173 (37.2%) RA with excess blasts (RAEB), and 86 (18.5%) RAEB in transformation (RAEBT). We found that those older at diagnosis (> 60 years of age) (HR = 1.68, CI = 1.26-2.25) were at a higher risk of dying compared to younger patients. Similarly, high pack years of smoking (>= 30 pack years of smoking) (HR = 1.34, CI = 1.02-1.74), and agricultural chemical exposure (HR = 1.61, CI = 1.05-2.46) were significantly associated with overall lower survival when compared to patients with none or medium exposures. Among clinical markers, greater than 5% bone marrow blasts (HR = 1.81 CI = 1.27-2.56), poor cytogenetics (HR = 3.20, CI = 2.37-4.33)), and platelet cytopenias (<100000/ul) (HR = 1.46, CI = 1.11-1.92) were also significantly associated with overall MDS survival.^ The identification of epidemiological markers could help physicians stratify patients and customize treatment strategies to improve the outcome of MDS based on patient lifestyle information such as smoking exposure and agrochemical exposure. We hope that this study highlights the impact of these exposures in MDS prognosis.^

Association of processed red meat and prostate cancer stage in Mexican-Americans: A population based case-control study

Objective: The objective of this study is to investigate the association between processed and unprocessed red meat consumption and prostate cancer (PCa) stage in a homogenous Mexican-American population. Methods: This population-based case-control study had a total of 582 participants (287 cases with histologically confirmed adenocarcinoma of the prostate gland and 295 age and ethnicity-matched controls) that were all residing in the Southeast region of Texas from 1998 to 2006. All questionnaire information was collected using a validated data collection instrument. Statistical Analysis: Descriptive analyses included Student's t-test and Pearson's Chi-square tests. Odds ratios and 95% confidence intervals were calculated to quantify the association between nutritional factors and PCa stage. A multivariable model was used for unconditional logistic regression. Results: After adjusting for relevant covariates, those who consume high amounts of processed red meat have a non-significant increased odds of being diagnosed with localized PCa (OR = 1.60 95% CI: 0.85 - 3.03) and total PCa (OR = 1.43 95% CI: 0.81 - 2.52) but not for advanced PCa (OR = 0.91 95% CI: 1.37 - 2.23). Interestingly, high consumption of carbohydrates shows a significant reduction in the odds of being diagnosed with total PCa and advanced PCa (OR = 0.43 95% CI: 0.24 - 0.77; OR = 0.27 95% CI: 0.10 - 0.71, respectively). However, consuming high amounts of energy from protein and fat was shown to increase the odds of being diagnosed with advanced PCa (OR = 4.62 95% CI: 1.69 - 12.59; OR = 2.61 95% CI: 1.04 - 6.58, respectively). Conclusion: Mexican-Americans who consume high amounts of energy from protein and fat had increased odds of being diagnosed with advanced PCa, while high amounts of carbohydrates reduced the odds of being diagnosed with total and advanced PCa.^

2-methylthio-N$\sp6$-dimethylallyl modification of adenosine 37 of tRNAs in {\it Escherichia coli\/} K-12

The hypermodified, hydrophobic 2-methylthio-N$\sp6$-(dimethylallyl)-adenosine (ms${2{\cdot}6}\atop1$A) residue occurs $3\sp\prime$ to the anticodon in tRNA species that read codons beginning with U. The first step (i$\sp6$A37 formation) of this modification is catalyzed by dimethylallyl diphosphate:tRNA dimethyallyltransferase (EC 2.5.1.8), which is the product of the miaA gene. Subsequent steps were proposed to be catalyzed by MiaB and MiaC enzymes to complete the ms${2{\cdot}6}\atop1$A37 modification. The study of functions of the ms${2{\cdot}6}\atop1$A37 is very important because this modified base is one of the best candidates for a role in global control in response to environmental stress. This dissertation describes the further delineation of functions of the ms${2{\cdot}6}\atop1$A37 modification in E. coli K-12 cells. This work provides significant information on functions of tRNA modifications in E. coli cells to adapt to stressful environmental conditions. Three hypotheses were tested in this work.^ The first hypothesis tested was that non-optimal translation processes cause increased spontaneous mutagenesis by the induction of SOS response in starving cells. To test this hypothesis, I measured spontaneous mutation rates of wild type cells and various mutant strains which are defective in tRNA modification, SOS response, or oxidative damage repair. I found that the miaA mutation acts as a mutator that increased Lac$\sp+$ reversion rates and Trp$\sp+$ reversion frequencies of the wild-type cells in starving conditions. However, the lexA3(Ind)(which abolishes the induction of SOS response) mutation abolished the mutator phenotype of the miaA mutant. The recA430 mutation, not other identified SOS genes, decreased the Lac$\sp+$ reversion to a less extent than that of the lexA3(Ind) mutation. These results suggest that RecA together with another unidentified SOS gene product are responsible for the process.^ The second hypothesis tested was that MiaA protein binds to full-length tRNA$\sp{\rm Phe}$ molecules in form of a protein dimer. To test this hypothesis, three versions of the MiaA protein and seven species of tRNA substrates were purified. Binding studies by gel mobility shift assays, filter binding assays and gel filtration shift assays support the hypothesis that MiaA protein binds to full-length tRNA$\sp{\rm Phe}$ as a protein dimer but as a monomer to the anticodon stem-and-loop. These results were further supported by using steady state enzyme kinetic studies.^ The third hypothesis tested in this work was that the miaB gene in E. coli exists and is clonable. The miaB::Tn10dCm insertion mutation of Salmonella typhimurium was transduced to E. coli K-12 cells by using P$\sb1$ and P$\sb{22}$ bacteriophages. The insertion was confirmed by HPLC analyses of nucleotide profiles of miaB mutants of E. coli. The insertion mutation was cloned and DNA sequences adjacent to the transposon were sequenced. These DNA sequences were 86% identical to the f474 gene at 14.97 min chromosome of E. coli. The f474 gene was then cloned by PCR from the wild-type chromosome of E. coli. The recombinant plasmid complemented the mutant phenotype of the miaB mutant of E. coli. These results support the hypothesis that the miaB gene of E. coli exists and is clonable. In summary, functions of the ms${2{\cdot}6}\atop1$A37 modification in E. coli cells are further delineated in this work in perspectives of adaptation to stressful environmental conditions and protein:tRNA interaction. (Abstract shortened by UMI.) ^