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Lead exposure causes thyroid abnormalities in diabetic rats. - International journal of clinical and experimental medicine
Lead is a widely-spread environmental pollutant and a commonly-used industrial chemical that can cause multisystemic adverse health effects. However, the effects of lead exposure on diabetic animals have not been reported so far. The aim of this study is to evaluate the effects of lead exposure on thyroid, renal and oxidative stress markers in diabetic Wistar rats. Diabetes was induced with an intraperitoneal (i.p.) injection of streptozocin (STZ). Six weeks later, rats were exposed i.p. to either distilled water (control group) or 25, 50 and 100 mg/kg of lead acetate (treatment groups). We found a positive relationship between the administered doses of lead acetate and its measured levels in blood samples (P < 0.01). Treatment of diabetic animals with lead acetate resulted in significant weight loss (P < 0.001). It also caused an increase in thyroid stimulating hormone levels (P < 0.05) and reductions in thyroxine (P < 0.05) and triiodothyronine levels (P < 0.01), a clinical picture consistent with hypothyroidism. Lead acetate exposure increased urea levels (P < 0.05) and caused a significant decrease in creatinine (P < 0.05). Besides, while the concentrations of malondialdehyde were not affected, glutathione stores were depleted (P < 0.01); in response to lead exposure. In conclusion, exposure of diabetic rats to lead acetate resulted in weight loss, clinical hypothyroidism, renal damage and oxidative stress.
Simultaneous regulation of cell size and chromosome replication in bacteria. - Frontiers in microbiology
Bacteria are able to maintain a narrow distribution of cell sizes by regulating the timing of cell divisions. In rich nutrient conditions, cells divide much faster than their chromosomes replicate. This implies that cells maintain multiple rounds of chromosome replication per cell division by regulating the timing of chromosome replications. Here, we show that both cell size and chromosome replication may be simultaneously regulated by the long-standing initiator accumulation strategy. The strategy proposes that initiators are produced in proportion to the volume increase and is accumulated at each origin of replication, and chromosome replication is initiated when a critical amount per origin has accumulated. We show that this model maps to the incremental model of size control, which was previously shown to reproduce experimentally observed correlations between various events in the cell cycle and explains the exponential dependence of cell size on the growth rate of the cell. Furthermore, we show that this model also leads to the efficient regulation of the timing of initiation and the number of origins consistent with existing experimental results.
Vanadium(V) removal from aqueous solution and real wastewater using quaternized pine sawdust. - Water science and technology : a journal of the International Association on Water Pollution Research
Cross-linked and quaternized pine sawdust was tested for vanadium removal from a synthetic aqueous solution as well as from real industrial wastewater which had a considerable amount of vanadium and other ions such as sulphate, ammonium and nickel. The maximum vanadium sorption capacity of the modified pine sawdust was found to be 130 mg/g in synthetic solution and 103 mg/g in real wastewater. Modified pine sawdust worked well over a wide range of pH. Column studies with real wastewater proved that vanadium was efficiently desorbed from the material with 2 M NaOH and that the material could be reused.
Developmental phonagnosia: Neural correlates and a behavioral marker. - Brain and language
A 20-year old female, AN, with no history of neurological events or detectable lesions, was markedly poorer than controls at identifying her most familiar celebrity voices. She was normal at face recognition and in discriminating which of two speakers uttered a particular sentence. She evidences normal fMRI sensitivity for human speech and non-speech sounds. AN, and two other phonagnosics, were unable to imagine the voices of highly familiar individuals. A region in the ventromedial prefrontal cortex (vmPFC) was differentially activated in controls when imagining familiar celebrity voices compared to imagining non-voice sounds. AN evidenced no differential activation in this area, which has been termed a person identity semantic system. Rather than a deficit in the representation of voice-individuating cues, AN may be unable to associate those cues to the identity of a familiar person. In this respect, the deficit in developmental phonagnosia may bear a striking parallel to developmental prosopagnosia.Copyright Â© 2015 Elsevier Inc. All rights reserved.
Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components. - Biologicals : journal of the International Association of Biological Standardization
The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar. At neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197 conjugates. This was verified in AlPO4 formulations containing DTwP-Hib, where the adsorption of TT-conjugated Hib was higher than CRM197-conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate ions reduced the binding of the conjugates to the adjuvants. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates.Copyright Â© 2015. Published by Elsevier Ltd.
Regulation of Elg1 activity by phosphorylation. - Cell cycle (Georgetown, Tex.)
ELG1 is a conserved gene with important roles in the maintenance of genome stability. Elg1`s activity prevents gross chromosomal rearrangements, maintains proper telomere length regulation, helps repairing DNA damage created by a number of genotoxins and participates in sister chromatid cohesion. Elg1 is evolutionarily conserved, and its Fanconi Anemia-related mammalian ortholog (also known as ATAD5) is embryonic lethal when lost in mice and acts as a tumor suppressor in mice and humans. Elg1 encodes a protein that forms an RFC-like complex that unloads the replicative clamp, PCNA, from DNA, mainly in its SUMOylated form. We have identified two different regions in yeast Elg1 that undergo phosphorylation. Phosphorylation of one of them, S112, is dependent on the ATR yeast ortholog, Mec1, and probably is a direct target of this kinase. We show that phosphorylation of Elg1 is important for its role at telomeres. Mutants unable to undergo phosphorylation suppress the DNA damage sensitivity of Î”rad5 mutants, defective for an error-free post-replicational bypass pathway. This indicates a role of phosphorylation in the regulation of DNA repair. Our results open the way to investigate the mechanisms by which the activity of Elg1 is regulated during DNA replication and in response to DNA damage.
Outcomes of Estrogen Receptor Negative and Progesterone Receptor Positive Breast Cancer. - PloS one
To describe the clinical features and outcomes of estrogen receptor negative (ER-) and progesterone receptor positive (PgR+) breast cancer.We retrospectively reviewed a well-characterized database of sequential patients diagnosed with early stage invasive breast carcinoma. Outcomes of interest were time to relapse (TTR) and overall survival (OS). Multivariable Cox proportional hazards analysis was conducted to assess the association of ER-/PgR+ with TTR and OS in comparison to ER+ and to ER- and PgR negative (ER-/PgR-) tumors irrespective of HER2 status. ER and PgR expression was conservatively defined as 10% or greater staining of cancer cells.815 patients were followed for a median of 40.5 months; 56 patients (7%) had ER-/PgR+, 624 (77%) had ER+ and 136 (17%) had ER-/PgR- phenotypes. Compared with ER+ tumors, ER-/PgR+ tumors were associated with younger age (50 versus 59 years, p=0.03), high grade (50% versus 24%, p<0.001) and more frequent HER2 overexpression/amplification (43% versus 14%, p<0.001). TTR for ER-/PgR+ was intermediate between ER+ and ER-/PgR- tumors, but was not significantly different from ER+ tumors. Recurrences in the ER-/PgR+ and ER-/PgR- groups occurred early in follow-up while in ER+ tumors recurrences continued to occur over the duration of follow-up. OS of ER-/PgR+ was similar to ER+ tumors and better than that of ER-/PgR- tumors.The ER-/PgR+ phenotype is associated with higher grade with HER2 overexpression/amplification and occurs more commonly in younger women. Risk of relapse and death more closely resembles ER+ than ER-/PgR- tumors suggesting this phenotype represents a group of more aggressive hormone receptor positive tumors.
Birth-Weight, Pregnancy Term, Pre-Natal and Natal Complications Related to Child's Dental Anomalies. - The Journal of clinical pediatric dentistry
This cross-sectional study was aimed at determining whether certain pre-natal and natal conditions can predict specific dental anomalies. The conditions observed were: low birth-weight, preterm birth, pre-natal & natal complications. The dental anomalies observed were: enamel defects, total number of decayed, missing and filled teeth (total DMFT), disturbances in the tooth shape and disturbances in the number of teeth.Out of more than 2000 medical files of children aged 2-17 years old which were reviewed, 300 files met the selection criteria. Information recorded from the files included: age, gender, health status (the ASA physical status classification system by the American Society of Anesthesiologists), birth week, birth weight, total DMFT, hypomineralization, abnormal tooth shape, abnormal number of teeth and hypoplasia.Twenty one children out of 300 (7%) were born after a high-risk pregnancy, 25 children (8.3%) were born after high-risk birth, 20 children (6.7%) were born preterm - before week 37, and 29 children (9.7%) were born with a low birth weight (LBW) - 2500 grams or less. A relationship between a preterm birth and LBW to hypomineralization was found. And a relationship between a preterm birth and high-risk pregnancy to abnormal number of teeth was found. No relationship was found between birth (normal/high-risk) and the other parameters inspected.Preterm birth and LBW may predict hypomineralization in both primary and permanent dentitions. Furthermore, the study demonstrated that preterm birth and high-risk pregnancy may predict abnormal number of teeth in both dentitions.
Drainoscopy: a doorway to the abdomen in the post-surgical patient. - Techniques in coloproctology
The ability to optically visualize the abdominal cavity in the post-surgical patient can prove to be invaluable, particularly when imaging studies and exam findings can be difficult to interpret. Post-surgical drains are often used and provide a window into the abdominal cavity. In this proof-of-concept study, it is demonstrated that an ordinary drain can be used as a point of access and hence a doorway into the abdominal cavity. This technique has been termed drainoscopy, and the approach is demonstrated with video supplement.
IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer. - Biochemical and biophysical research communications
IL-15 has pivotal roles in the control of CD8(+) memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-Î³ production, the different inÂ vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-Î³ in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-Î³ production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-Î³ production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-Î³ production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion inÂ vitro, a crucial step in adoptive T cell therapy.Copyright Â© 2015 Elsevier Inc. All rights reserved.
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