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Mapping transcription factor interactome networks using HaloTag protein arrays

Yazaki, Junshi; Galli, Mary; Kim, Alice Y; Nito, Kazumasa; Aleman, Fernando; Chang, Katherine N; Carvunis, Anne-Ruxandra; Quan, Rosa; Nguyen, Hien; Song, Liang; Alvarez, José M; Huang, Shao-Shan Carol; Chen, Huaming; Ramachandran, Niroshan; Altmann, Stefan; Gutiérrez, Rodrigo A; Hill, David E; Schroeder, Julian I; Chory, Joanne; LaBaer, Joshua; Vidal, Marc; Braun, Pascal; Ecker, Joseph R
Protein microarrays enable investigation of diverse biochemical properties for thousands of proteins in a single experiment, an unparalleled capacity. Using a high-density system called HaloTag nucleic acid programmable protein array (HaloTag-NAPPA), we created high-density protein arrays comprising 12,000 Arabidopsis ORFs. We used these arrays to query protein-protein interactions for a set of 38 transcription factors and transcriptional regulators (TFs) that function in diverse plant hormone regulatory pathways. The resulting transcription factor interactome network, TF-NAPPA, contains thousands of novel interactions. Validation in a benchmarked in vitro pull-down assay revealed that a random subset of TF-NAPPA validated at the same rate of 64% as a positive reference set of literature-curated interactions. Moreover, using a bimolecular fluorescence complementation (BiFC) assay, we confirmed in planta several interactions of biological interest and determined the interaction localizations for seven pairs. The application of HaloTag-NAPPA technology to plant hormone signaling pathways allowed the identification of many novel transcription factor-protein interactions and led to the development of a proteome-wide plant hormone TF interactome network.
PMID: 27357687
ISSN: 1091-6490
CID: 3209312

A case report of adalimumab-associated optic neuritis

Kim, Alice; Saffra, Norman
PURPOSE: To describe a case of retrobulbar optic neuritis that presented within 3 weeks of adalimumab treatment initiation. METHODS: This index case was evaluated with visual field testing, brain magnetic resonance imaging, lumbar puncture, and laboratory evaluation, and treated with intravenous methylprednisolone followed by a steroid taper. RESULTS: Our patient made a full visual recovery, but was found to have extensive T2/FLAIR foci of hyperintensities that enhanced and had restricted diffusion on magnetic resonance imaging (MRI). Six months later, these demyelinating lesions still persisted and our patient was initiated on immunomodulatory treatment. CONCLUSION: With the extensive burden of disease at presentation and persistence of lesions on follow-up MRI, this unusual case seems to suggest an unmasking of an underlying demyelinating process by adalimumab. The clinician should be mindful of this association and monitor for any manifestations and treat appropriately.
PMID: 22271346
ISSN: 1869-5760
CID: 210912

Pelvic ultrasound immediately following MDCT in female patients with abdominal/pelvic pain: is it always necessary?

Yitta, Silaja; Mausner, Elizabeth V; Kim, Alice; Kim, Danny; Babb, James S; Hecht, Elizabeth M; Bennett, Genevieve L
To determine the added value of reimaging the female pelvis with ultrasound (US) immediately following multidetector CT (MDCT) in the emergent setting. CT and US exams of 70 patients who underwent MDCT for evaluation of abdominal/pelvic pain followed by pelvic ultrasound within 48 h were retrospectively reviewed by three readers. Initially, only the CT images were reviewed followed by evaluation of CT images in conjunction with US images. Diagnostic confidence was recorded for each reading and an exact Wilcoxon signed rank test was performed to compare the two. Changes in diagnosis based on combined CT and US readings versus CT readings alone were identified. Confidence intervals (95%) were derived for the percentage of times US reimaging can be expected to lead to a change in diagnosis relative to the diagnosis based on CT interpretation alone. Ultrasound changed the diagnosis for the ovaries/adnexa 8.1% of the time (three reader average); the majority being cases of a suspected CT abnormality found to be normal on US. Ultrasound changed the diagnosis for the uterus 11.9% of the time (three reader average); the majority related to the endometrial canal. The 95% confidence intervals for the ovaries/adnexa and uterus were 5-12.5% and 8-17%, respectively. Ten cases of a normal CT were followed by a normal US with 100% agreement across all three readers. Experienced readers correctly diagnosed ruptured ovarian cysts and tubo-ovarian abscesses (TOA) based on CT alone with 100% agreement. US reimaging after MDCT of the abdomen and pelvis is not helpful: (1) following a normal CT of the pelvic organs or (2) when CT findings are diagnostic and/or characteristic of certain entities such as ruptured cysts and TOA. Reimaging with ultrasound is warranted for (1) less-experienced readers to improve diagnostic confidence or when CT findings are not definitive, (2) further evaluation of suspected endometrial abnormalities. A distinction should be made between the need for immediate vs. follow-up imaging with US after CT
PMID: 21638034
ISSN: 1438-1435
CID: 137438

Isolated sixth cranial nerve palsy as the presenting symptom of a rapidly expanding ACTH positive pituitary adenoma: a case report

Saffra, Norman; Kaplow, Elizabeth; Mikolaenko, Irina; Kim, Alice; Rubin, Benjamin; Jafar, Jafar
BACKGROUND: Pituitary adenoma may present with neuro-ophthalmic manifestations and, typically, rapid tumor expansion is the result of apoplexy. Herein, we present the first case of an isolated sixth cranial nerve palsy as initial feature of a rapidly expanding ACTH positive silent tumor without apoplexy. CASE PRESENTATION: A 44 year old female with a history of sarcoidosis presented with an isolated sixth cranial nerve palsy as the initial clinical feature of a rapidly expanding ACTH positive silent pituitary adenoma. The patient underwent emergent transsphenoidal hypophysectomy for this rapidly progressive tumor and subsequently regained complete vision and ocular motility. Despite tumor extension into the cavernous sinus, the other cranial nerves were spared during the initial presentation. CONCLUSIONS: This case illustrates the need to consider a rapidly growing pituitary tumor as a possibility when presented with a rapidly progressive ophthalmoplegia
PMID: 21272327
ISSN: 1471-2415
CID: 143652

Correlation of apparent diffusion coefficient with neuropsychological testing in temporal lobe epilepsy

Lui, Yvonne W; Nusbaum, Annette O; Barr, William B; Johnson, Glyn; Babb, James S; Orbach, Darren; Kim, Alice; Laliotis, Georgia; Devinsky, Orrin
BACKGROUND AND PURPOSE: Patients with nonlesional temporal lobe epilepsy have long been known to have abnormalities of memory. Recently, these patients have been shown to have increased diffusivity in the hippocampus. We hypothesized that in these patients, a negative correlation would exist between diffusivity measures of the mesial temporal lobe and performance on neuropsychological tests. METHODS: Twenty presurgical patients with temporal lobe epilepsy and 20 age- and sex-matched healthy controls underwent MR imaging of the brain. Apparent diffusion coefficient region of interest measures were taken in both hippocampi and parahippocampal gyri by 2 independent observers. Mean whole brain diffusivity was calculated. All patients completed neuropsychological testing. Electroencephalogram and pathology results were collected. Patients and controls were compared with respect to each apparent diffusion coefficient measure. In patients, apparent diffusion coefficients ipsilateral and contralateral to the seizure focus were compared. Associations were assessed between diffusivity measures and neuropsychological scores. RESULTS: Eleven patients had right-sided seizure foci and 9 had left-sided seizure foci. Patients demonstrated higher apparent diffusion coefficient values than controls over the whole brain, in the hippocampi, and in the parahippocampal gyri (P < .05). Patients demonstrated higher apparent diffusion coefficient within the ipsilateral hippocampus (1.19 +/- 0.22 x 10(-3) s/mm2) and parahippocampal gyrus (1.02 +/- 0.12 x 10(-3) s/mm2) compared with the contralateral side (1.02 +/- 0.16 x 10(-3) s/mm2 and 0.96 +/- 0.09 x 10(-3) s/mm2, respectively) (P < .05). Negative correlations were seen between hippocampal apparent diffusion coefficients and multiple memory tests (P < .05). CONCLUSION: Quantitative diffusion measurements in the hippocampus correlate with memory dysfunction in patients with temporal lobe epilepsy
PMID: 16091538
ISSN: 0195-6108
CID: 57871

Paclitaxel-induced apoptosis and mitotic arrest assessed by serial fine-needle aspiration: implications for early prediction of breast cancer response to neoadjuvant treatment

Symmans WF; Volm MD; Shapiro RL; Perkins AB; Kim AY; Demaria S; Yee HT; McMullen H; Oratz R; Klein P; Formenti SC; Muggia F
The extent of tumor reduction from neoadjuvant chemotherapy for breast cancer correlates with outcome. We investigated whether the initial cellular responses to paclitaxel are related to the extent of tumor reduction. Eleven women with breast cancer received paclitaxel (every 2 weeks for 4 cycles) as neoadjuvant treatment. Serial fine-needle aspirations (FNA; 25-gauge, 1 pass) were obtained before treatment and at 24, 48, 72, and 96 h after the first paclitaxel dose. Microscopic counts of apoptotic and mitotic indices were performed. The change in cancer volume from treatment was determined using radiological measurements with allowance for change in the histopathological amount of cancer. Apoptotic and mitotic responses usually subsided within 4 days. The duration of the initial apoptotic response was different for women with different treatment results. Cumulative apoptotic response for the first 4 days inversely correlated with the proportion of residual cancer after neoadjuvant treatment. FNA is a versatile clinical method to obtain breast cancer cells for therapy response studies. Apoptotic response to the first dose of paclitaxel is almost complete within 4 days, implying that more frequent (weekly) paclitaxel dosing might be beneficial. The apoptotic response to the first dose of paclitaxel appeared to predict the amount of cancer reduction from this treatment. This is a promising start toward the development of an early chemopredictive assay for paclitaxel treatment of breast cancer
PMID: 11156210
ISSN: 1078-0432
CID: 22642

Small-bowel obstruction associated with sigmoid diverticulitis: CT evaluation in 16 patients

Kim AY; Bennett GL; Bashist B; Perlman B; Megibow AJ
OBJECTIVE: The purpose of this study was to identify acute sigmoid diverticulitis as a cause of small-bowel obstruction and to describe the CT findings. CONCLUSION: CT scanning enabled accurate preoperative diagnosis of colonic diverticulitis as the cause of the small-bowel obstruction, thereby allowing proper management and surgical planning
PMID: 9574608
ISSN: 0361-803x
CID: 7627