1000 Wall St
Ann Arbor MI 48105
Medical School: Other - Unknown
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License #: P24456
Taxonomy Codes:207R00000X 207W00000X
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Cytokines are both villains and potential therapeutic targets in thyroid-associated ophthalmopathy: From bench to bedside. - Expert review of ophthalmology
The pathophysiology underlying Graves' disease and its ocular manifestation, thyroid associated ophthalmopathy (TAO) is incompletely understood. Characterization of the mononuclear cells driving the disease and the cytokines they produce has led to significant advances in our understanding of TAO. This in turn has resulted in the identification of potentially attractive drug targets. For instance, development of inhibitors of specific cytokine pathways for use in other autoimmune diseases now presents an opportunity for their application in TAO. In this paper, we review the rationale for considering anti-cytokine therapy in TAO, evidence linking specific cytokines such as interleukin-6, tumor necrosis factor-Î±, and interleukin-17 pathways to TAO, and explore the potential for targeting of these pathways as therapy.
The demethylating agent 5-Aza reduces the growth, invasiveness, and clonogenicity of uveal and cutaneous melanoma. - Investigative ophthalmology & visual science
Uveal melanoma is the most common primary intraocular malignancy in adults. Although local disease can be controlled with radiation therapy or enucleation, many cases are complicated by metastases, which account for the significant mortality from this disease. To date, no chemotherapeutic regimens effectively treat local or metastatic disease. Epigenetic silencing of tumor suppressor genes has been shown to be an important factor in the growth and metastasis of many cancers. One form of epigenetic alteration is DNA methylation, which often occurs at promoter elements resulting in the silencing of target gene transcription.We used 5-aza-2'-deoxycytidine (5-Aza), a well characterized demethylating agent that is US Food and Drug Administration approved to decrease DNA methylation in multiple uveal and cutaneous melanoma cell lines.Demethylation of melanoma cell lines using 5-Aza causes significant decreases in growth, invasion, and clonogenicity. Treatment of melanoma cells with combined 5-Aza therapy and irradiation showed an even more pronounced effect on cell viability. In addition, treatment with 5-Aza decreased the number of metastases from the eye to the lung in a murine cutaneous melanoma xenograft model.We demonstrate in vitro and in vivo that demethylating agents such as 5-Aza may be promising chemotherapeutic agents for treating melanoma and decreasing progression to metastatic disease. These results provide proof of concept for an exciting potential therapy to reduce mortality from this disease. Future work will focus on identifying pathways that mediate these changes.Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Cataract surgery in patients with left ventricular assist device support. - Journal of cataract and refractive surgery
Left ventricular assist devices (LVADs) have been increasingly used for 20 years in terminally ill patients with advanced heart failure or awaiting cardiac transplantation. Despite improvement in morbidity and mortality from use of these devices, quality of life may be limited by cataract. Access to cataract surgery in this predominantly elderly population is essential but limited by unfamiliarity with these devices. We describe phacoemulsification and intraocular lens implantation in 2 patients with LVADs. The patients had extensive preoperative cardiology evaluations and were instructed to continue warfarin through the day of surgery. Monitored sedation was used with fentanyl and midazolam. Both patients experienced significant improvement in visual acuity and quality of life. Neither experienced intraoperative hemodynamic instability. Cataract surgery may be safely performed in patients with LVAD support when adequate monitoring resources are available.No author has a financial or proprietary interest in any material or method mentioned.Copyright Â© 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Intratarsal keratinous cyst - an emerging entity. - Case reports in ophthalmology
We report two cases of recurrent intratarsal keratinous cysts of the Meibomian gland, a recently described lesion thought to have been previously misdiagnosed. The correct diagnosis can be made based on histopathologic features alone, although expression of cytokeratin (CK) 5/6 in the cyst epithelium is a specific marker of these lesions. Recognition of these lesions, and distinguishing them from other intratarsal cysts that do not recur, is important to guide definitive therapy via full-thickness excision rather than simple incision and drainage.
Expression of the dominant negative retinoid receptor, RAR403, alters telencephalic progenitor proliferation, survival, and cell fate specification. - Developmental biology
Retinoic acid (RA) signaling plays critical roles in diverse cellular processes during nervous system development. In mouse models, the roles for RA signals in telencephalic development remain unclear, partly because of the ambiguity of RA telencephalic sources after E8.75. Here, we have developed a genetic approach that utilizes Cre-lox technology to conditionally express a potent dominant negative retinoid receptor, RAR403, in vivo. This approach blocks RA signaling pathways at the receptor level, enabling the disruption of RA signals in contexts in which the RA source is unknown. RAR403 expression throughout the developing telencephalon causes pronounced hypoplasia resulting from defective proliferation in dorsal telencephalic progenitors and extensive cell death. Furthermore, Nkx2.1(+) progenitors in the medial ganglionic eminence (MGE) are misspecified such that they acquire a subset of lateral ganglionic eminence (LGE)-specific properties at the expense of MGE fates. This genetic approach reveals new roles for RA signaling in telencephalic proliferation, survival and fate specification, and underscores its utility in investigating the function of retinoid signaling pathways throughout peri- and postnatal development.
pp32 reduction induces differentiation of TSU-Pr1 cells. - The American journal of pathology
pp32 (ANP32A) is a nuclear phosphoprotein expressed as a nonmutated form in self-renewing cell populations and neoplastic cells. Mechanistically, pp32 may regulate pathways important in the process of differentiation as part of separate complexes inhibiting histone acetylation and regulating immediate-early and cytokine mRNA stability. Prostatic adenocarcinomas express pp32 in a differentiation related manner-well-differentiated tumors express lower levels of pp32 than poorly differentiated tumors. In benign prostate, pp32 is expressed in basal cells but not in terminally differentiated glandular cells. Based on these observations, we hypothesized that reduction of pp32 expression might be an important differentiation signal. We used anti-sense pp32 and RNAi transfection to study the effects of reduced pp32 expression in the TSU-Pr1 carcinoma cell line. pp32 reduction induced TSU-Pr1 cells to differentiate into neuronal-like cells with associated inhibition of growth. Reduction of pp32 and consequent differentiation were accompanied by a marked reduction in expression of SET, which complexes with pp32, by a marked change in acetylation status of histone H4, and by further differential expression of genes in differentiation pathways. Thus, reduction of pp32 in the undifferentiated TSU-Pr1 neoplastic cell line induces differentiation and thus may be an element of a differentiation control pathway in both normal and neoplastic cells.
Intralesional Rituximab for the Treatment of Recurrent Ocular Adnexal Lymphoma. - Ophthalmic plastic and reconstructive surgery
A 41-year-old female with Sjogren syndrome presented with a 5-month history of bilateral upper eyelid swelling. Incisional biopsy of the left lacrimal gland revealed mucosa-associated lymphoid tissue lymphoma. Due to bilateral severe dry eyes, the patient declined external beam radiotherapy and systemic rituximab was initiated. The patient responded well to intravenous rituximab and the follow-up CT revealed decrease in size of both lacrimal glands. Eleven months after systemic rituximab, the patient developed bilateral lacrimal gland recurrence. The patient declined external beam radiotherapy. Intralesional rituximab (50 mg/1 ml) was injected into the left lacrimal gland, followed by injection in the right lacrimal gland 7 months later. Twenty-three months follow-up after the injection into the right lacrimal gland, there was significant decrease in size of bilateral lacrimal glands and subjective improvement of dry eye symptoms. This case highlights the intralesional rituximab as an alternative therapy for recurrent orbital mucosa-associated lymphoid tissue lymphoma in selected cases.
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1000 Wall St Ann Arbor, MI 48105
24 Frank Lloyd Wright Dr Lobby A
2215 Fuller Rd Vamc Dental Service (160)