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1.  A Synthetic Model of Human Beta-Thalassemia Erythropoiesis Using CD34+ Cells from Healthy Adult Donors 
PLoS ONE  2013;8(7):e68307.
Based upon the lack of clinical samples available for research in many laboratories worldwide, a significant gap exists between basic and clinical studies of beta-thalassemia major. To bridge this gap, we developed an artificially engineered model for human beta thalassemia by knocking down beta-globin gene and protein expression in cultured CD34+ cells obtained from healthy adults. Lentiviral-mediated transduction of beta-globin shRNA (beta-KD) caused imbalanced globin chain production. Beta-globin mRNA was reduced by 90% compared to controls, while alpha-globin mRNA levels were maintained. HPLC analyses revealed a 96% reduction in HbA with only a minor increase in HbF. During the terminal phases of differentiation (culture days 14–21), beta-KD cells demonstrated increased levels of insoluble alpha-globin, as well as activated caspase-3. The majority of the beta-KD cells underwent apoptosis around the polychromatophilic stage of maturation. GDF15, a marker of ineffective erythropoiesis in humans with thalassemia, was significantly increased in the culture supernatants from the beta-KD cells. Knockdown of beta-globin expression in cultured primary human erythroblasts provides a robust ex vivo model for beta-thalassemia.
doi:10.1371/journal.pone.0068307
PMCID: PMC3704632  PMID: 23861885
2.  Prevalence of Uterine Leiomyomas in Lymphangioleiomyomatosis 
Fertility and sterility  2011;96(3):711-714.e1.
Objective
To determine the frequency of uterine leiomyomas and hysterectomy in patients with lymphangioleiomyomatosis (LAM), a disease characterized by proliferation of abnormal-appearing smooth muscle-like cells.
Design
Retrospective study.
Patients
456 patients with sporadic LAM and LAM associated with tuberous sclerosis complex (LAM/TSC).
Setting
Natural history study at the National Institutes of Health.
Intervention(s)
Review of records and pelvic computed axial tomography scans.
Main Outcome Measure(s)
prevalence of uterine leiomyomas and hysterectomy.
Results
A total of 174 women had uterine leiomyomas (38%). One hundred eighteen were diagnosed by CT scan and 56 were diagnosed by hysterectomy. Among 323 patients who did not have hysterectomy, 105 of 270 patients (39%) with sporadic LAM and 13 of 53 (25%) with LAM/TSC had uterine leiomyomas. Hysterectomy was performed in 108 of 378 subjects with sporadic LAM and 25 of 78 with LAM/TSC. Fifty six patients were found to have uterine fibroids at hysterectomy. The most common indications for hysterectomy were uterine leiomyoma, lymphangioleiomyomatosis and endometriosis.
Conclusions
Uterine leiomyomas are not more common in LAM than in the general population. However, in LAM, the frequency of hysterectomy is higher because of it having been recommended for treatment of LAM.
doi:10.1016/j.fertnstert.2011.06.038
PMCID: PMC3165169  PMID: 21880281
Uterine leiomyomas; hysterectomy; lymphangioleiomyomatosis
3.  Expression of growth differentiation factor 15 is not elevated in individuals with iron deficiency secondary to volunteer blood donation 
Transfusion  2010;50(7):1532-1535.
BACKGROUND
Low serum hepcidin levels provide a physiologic response to iron demand in patients with iron deficiency (ID). Based on a discovery of suppressed hepcidin expression by a cytokine named growth differentiation factor 15 (GDF15), it was hypothesized that GDF15 may suppress hepcidin expression in humans with ID due to blood loss.
STUDY DESIGN AND METHODS
To test this hypothesis, GDF15 and hepcidin levels were measured in peripheral blood from subjects with iron-deficient erythropoiesis before and after iron supplementation.
RESULTS
Iron variables and hepcidin levels were significantly suppressed in iron-deficient blood donors compared to healthy volunteers. However, ID was not associated with elevated serum levels of GDF15. Instead, iron-deficient subjects’ GDF15 levels were slightly lower than those measured in the control group of subjects (307 ± 90 and 386 ± 104 pg/mL, respectively). Additionally, GDF15 levels were not significantly altered by iron repletion.
CONCLUSIONS
ID due to blood loss is not associated with a significant change in serum levels of GDF15.
doi:10.1111/j.1537-2995.2010.02601.x
PMCID: PMC3282986  PMID: 20210929
4.  HEPCIDIN, ANAEMIA, AND PROSTATE CANCER 
Bju International  2011;107(4):678-679.
doi:10.1111/j.1464-410X.2011.10108.x
PMCID: PMC3277454  PMID: 21276178
5.  Sporadic Lymphangioleiomyomatosis and Tuberous Sclerosis Complex with Lymphangioleiomyomatosis: Comparison of CT Features1 
Radiology  2006;242(1):277-285.
Purpose
To retrospectively compare the frequencies of computed tomographic (CT) findings in patients with lymphangioleiomyomatosis (LAM) and patients with tuberous sclerosis complex (TSC) and LAM.
Materials and Methods
Institutional review board approval and informed consent were obtained for the HIPAA-compliant study. In 256 patients with LAM (mean age, 44 years) and 67 patients with TSC/LAM (mean age, 40 years), CT scans of the chest, abdomen, and pelvis were reviewed by a single radiologist. The fraction of lung involvement with cysts was estimated from high-spatial-resolution CT scans. Other findings assessed included noncalcified pulmonary nodules, pleural effusion, thoracic duct dilatation, hepatic and renal angiomyolipomas (AMLs), lymphangioleiomyoma (LALM), ascites, nephrectomy, and renal embolization. Confidence intervals and hypothesis tests of differences in frequencies, comparison of age quartiles, RIDIT analysis, analysis of variance, and correlation coefficients were used in the statistical analysis.
Results
Patients with LAM had more extensive lung involvement (RIDIT score, 0.36) and higher frequency of LALM (29% vs 9%, P < .001), thoracic duct dilatation (4% vs 0, P = .3), pleural effusion (12% vs 6%, P = .2), or ascites (10% vs 6%, P = .3). Patients with TSC/LAM had higher frequency of noncalcified pulmonary nodules (12% vs 1%, P < .01), hepatic (33% vs 2%, P < .001) and renal (93% vs 32%, P < .001) AMLs, nephrectomy (25% vs 7%, P < .001), or renal artery embolization (9% vs 2%, P < .05).
Conclusion
The extent of lung disease is greater in LAM than TSC/LAM. Hepatic and renal AMLs and noncalcified lung nodules are more common in TSC/LAM, while lymphatic involvement—thoracic duct dilatation, chylous pleural effusion, ascites, and LALM—is more common in LAM.
doi:10.1148/radiol.2421051767
PMCID: PMC2940246  PMID: 17105849

Results 1-5 (5)