Dalia M Mikhael

Interests

Teaching

Medical student and residency education, effective and efficient inpatient care

Research

As above

Courses

Scholarly Contributions

Journals/Publications

• Mikhael, D. M., Babiker, H. M., Betancourt, R., Maestas, T., & Bailey, M. (2019). A Rare Cause of Thrombotic Thrombocytopenia Purpura- (TTP-) Like Syndrome, Vitamin B12 Deficiency: Interpretation of Significant Pathological Findings. Case reports in hematology. doi:10.1155/2019/1529306
• Hakim, I., Garland, L., Cordova, C., & Mikhael, D. M. (2017). Modulation of Oxidative Damage by Green and Black Tea: Role of Smoking and Gender in a Randomized Trial. Journal of Nutrition & Food Sciences, 7(633). doi:10.4172/2155-9600.1000633
• Hakim, I. A., Harris, R., Garland, L., Cordova, C. A., Mikhael, D. M., & Sherry Chow, H. (2012). Gender difference in systemic oxidative stress and antioxidant capacity in current and former heavy smokers. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 21(12), 2193-200.
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  Several studies suggested that women may be more susceptible to oxidative damage induced by cigarette smoking, but the role of smoking status and antioxidant capacity in gender difference in susceptibility to oxidative damage has not been well studied.
• Chow, H. S., Hakim, I. A., Vining, D. R., Crowell, J. A., Tome, M. E., Ranger-Moore, J., Cordova, C. A., Mikhael, D. M., Briehl, M. M., & Alberts, D. S. (2007). Modulation of human glutathione s-transferases by polyphenon e intervention. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 16(8), 1662-6.
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  Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Induction of detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer-preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea polyphenol administration on a major group of detoxification enzymes, glutathione S-transferases (GST).
• Goodman, L., Harris, R. B., Mikhael, D. M., Cordova, C. A., Tobar, M., Rodney, S., Garland, L. L., Hakim, I. A., & Chow, H. S. (2006).

  Gender differences in smoking-induced DNA damage.

  . Cancer Epidemiology and Prevention Biomarkers, 15.
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  B54 Background: Oxidative reactions have been implicated as important modulators of human health and can play a role in both disease prevention and disease development. A large number of studies have demonstrated an increased oxidant burden and consequently increased markers of oxidative stress in the blood, and urine of patients with chronic obstructive pulmonary disease (COPD).The overall goal of this study is to explore the association between urinary markers of DNA damage as measured by 8-hydroxydeoxyguanosine ( 8-OhDG), antioxidant enzymes, and FEV1/FVC among smokers and former smokers with different levels of pulmonary obstruction. Methods : Cross-sectional analysis of data from baseline samples from participants in an ongoing chemoprevention trial. The study participants provided blood and urine samples which were used for the analysis of 8-OHdG, superoxide dismutase (SOD) and catalase (CAT) levels. All statistical analyses (descriptive & linear regressions) were performed using STATA. Results : The study protocol was approved by all parties in April 2004. A total of 119 COPD (mean FEV1/FVC = 65.7 ± 13.5) subjects (61 females and 58 males)were included in the study. Fifty nine percent were former smokers and 41% current smokers, with a mean pack year of 49.2±23.5. Urinary 8-OHdG levels were significantly associated with sex (p=0.0008), with females having higher levels of DNA damage regardless of theis smoking status or pack/years. Catalase levels were significantly associated with pack years (p=0.019) when sex was also considered (p=0.057). SOD levels were not associated with any of the studied variables. As expected FEV1/FVC was significantly associated with pack years in the study population (p=0.0058), however, this association was mainly significant among males (p=0.0489) compared to females(p=0.2023). Conclusions : Among older adult smokers and former smokers, females have higher levels of DNA damage than males as measured by urinary 8-OHdG even after controlling for smoking. Catalase activity has a negative association with pack years, and is lower among female subjects. FEV1/FVC was associated with pack years - as we expected more smoking is associated with lower lung function - but more significantly among males No significant relationship between FEV1/FVC and pack years was found among females. In summary, it seems that female smokers are much more prone to oxidative stress as compared to male smokers. More studies are needed to explore the role of gender in susceptibility to DNA damage among smokers.
• Mikhael, D. M., Alberts, D. S., Chow, H. S., Cordova, C. A., Crowell, J. A., Hakim, I. A., Ranger-moore, J., & Vining, D. R. (2006).

  Effects of green tea catechin intervention on human Phase II detoxification enzymes.

  . Cancer Epidemiology and Prevention Biomarkers, 15.
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  Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 B152 Purpose: Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Modulation of carcinogen activation and detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea catechin administration on human Phase II detoxification enzymes. Methods: Forty-two healthy volunteers underwent a 4-week washout period by refraining from tea or tea related products. At the end of the washout period, a fasting blood sample was collected, and serum and lymphocytes were isolated for assessment of glutathione S-transferase (GST) activity and level. Following the baseline evaluation, study participants underwent 4 weeks of green tea catechin intervention at a dose that contains 800 mg epigallocatechin gallate once a day. Upon completion of the green tea catechin intervention, a fasting blood sample was collected and serum and lymphocytes isolated for post-intervention GST assessment. Serum total bilirubin levels were analyzed before and after repeated green tea catechin administration as a surrogate measurement of UDP-glucuronosyltransferase (UGT) 1A1 enzyme activity. Results: Four weeks of green tea catechin intervention significantly enhanced the GST activity and GST-π levels in peripheral blood lymphocytes in individuals with baseline activity or level in the lowest tertile. Repeated green tea catechin administration had minimal effects on plasma GST-α level. Furthermore, green tea catechin intervention significantly lowered serum bilirubin levels, implicating an induction of UGT1A1 activity, in individuals with baseline bilirubin levels in the highest tertile. Conclusions: We conclude that repeated green tea catechin administration induced GST and UGT1A1 activity in individuals with low baseline enzyme activity. This suggests that green tea catechin intervention would enhance the detoxification of carcinogens in individuals with low baseline detoxification capacity.
• Vazdarjanova, A., Ramirez-Amaya, V., Insel, N., Plummer, T. K., Rosi, S., Chowdhury, S., Mikhael, D., Worley, P. F., Guzowski, J. F., & Barnes, C. A. (2006). Spatial exploration induces ARC, a plasticity-related immediate-early gene, only in calcium/calmodulin-dependent protein kinase II-positive principal excitatory and inhibitory neurons of the rat forebrain. The Journal of comparative neurology, 498(3), 317-29.
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  Active behavior, such as exploring a novel environment, induces the expression of the immediate-early gene Arc (activity-regulated cytoskeletal associated protein, or Arg 3.1) in many brain regions, including the hippocampus, neocortex, and striatum. Arc messenger ribonucleic acid and protein are localized in activated dendrites, and Arc protein is required for the maintenance of long-term potentiation and memory consolidation. Although previous evidence suggests that Arc is expressed in neurons, there is no direct demonstration that only neurons can express Arc. Furthermore, there is no characterization of the main neuronal types that express Arc. The data reported here show that behavior- or seizure-induced Arc expression in the hippocampus, primary somatosensory cortex, and dorsal striatum of rats colocalizes only with neuronal (NeuN-positive) and not with glial (GFAP-positive) cells. Furthermore, Arc was found exclusively in non-GABAergic alpha-CaMKII-positive hippocampal and neocortical neurons of rats that had explored a novel environment. Some GAD65/67-positive neurons in these regions were observed to express Arc, but only after a very strong stimulus (electroconvulsive seizure). In the dorsal striatum, spatial exploration induced Arc only in GABAergic and alpha-CaMKII-positive neurons. Combined, these results show that although a very strong stimulus (seizure) can induce Arc in a variety of neurons, behavior induces Arc in the CaMKII-positive principal neurons of the hippocampus, neocortex, and dorsal striatum. These results, coupled with recent in vitro findings of interactions between Arc and CaMKII, are consistent with the hypothesis that Arc and CaMKII act as plasticity partners to promote functional and/or structural synaptic modifications that accompany learning.
• Ramírez-Amaya, V., Vazdarjanova, A., Mikhael, D., Rosi, S., Worley, P. F., & Barnes, C. A. (2005). Spatial exploration-induced Arc mRNA and protein expression: evidence for selective, network-specific reactivation. The Journal of neuroscience : the official journal of the Society for Neuroscience, 25(7), 1761-8.
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  The immediate-early gene Arc is transcribed in neurons that are part of stable neural networks activated during spatial exploratory behaviors. Arc protein has been demonstrated to regulate AMPA-type glutamate receptor trafficking by recruiting endosomal pathways, suggesting a direct role in synaptic plasticity. The purpose of the present study is to examine the fidelity of Arc mRNA translation and the temporal dynamics of behaviorally induced Arc protein expression after rats explore a novel environment. These experiments reveal two waves of Arc protein expression after a single exploration session. In the initial wave, virtually all cells that express Arc mRNA in the hippocampus and parietal cortex also express Arc protein, indicating, at a cellular level, that mRNA transcription and translation are closely correlated from 30 min to 2 h in hippocampal CA and parietal neurons. A second wave of protein expression spans the interval from 8 to 24 h and is also remarkably specific to cells active in the original behavior-induced network. This second wave is detected in a subset of the original active network and displays the novel property that the proportions of Arc-positive neurons become correlated among regions at 24 h. This suggests that the second expression wave is driven by network activity, and the stabilization of circuits reflecting behavioral experience may occur in temporally discrete phases, as memories become consolidated. This is the first demonstration of network-selective translational events consequent to spatial behavior and suggests a role for immediate-early genes in circuit-specific, late-phase synaptic biology.

Presentations

• Mikhael, D. (2022, September). Strategies for Challenging Patient Situations and Residents as Teachers Education . Internal medicine residency academic half day. University of Arizona, Tucson AZ.
• Mikhael, D. (2021, October). Pleural Effusions Diagnosis and Management. Internal Medicine Grand Rounds Clinicopathological Conference. University of Arizona, Tucson AZ.
• Mikhael, D. M. (2019, October). Ask-Tell-Ask on the Wards an Ignite Presentation. ACP Arizona Chapter. Tucson, AZ.
• Mikhael, D. M., Meinke, L. E., Ellis, S. C., & Scott, S. (2019, May). Innovations Quickfire: Residents as Teachers. Graduate Medical Education (GME). Tucson, AZ.

Case Studies

• Bailey, M., Maestas, T., Mikhael, D. M., & Babiker, H. M. (2019. A Rare Cause of Thrombotic Thrombocytopenia Purpura (TTP)-Like Syndrome, Vitamin B12 Deficiency: Interpretation of Significant Pathological Findings(pp NA).