Medical Specialties Commons^™

Identification Of A Unique Core Domain Of Par-4 Sufficient For Selective Apoptosis Induction In Cancer Cells, Vivek M. Rangnekar

Radiation Medicine Faculty Patents

The present invention relates to Par-4 mutants which cause apoptosis in cancer cells which are sensitive to Par-4 and also induce apoptosis in cancer cells which are resistant to Par-4. The present invention also relates to methods of using the Par-4 mutant to treat certain cancers, as well as to kits, vectors, and polypeptides for same.

Inhibition Of Allogeneic Inflammatory Responses By The Ribonucleotide Reductase Inhibitors, Didox And Trimidox, Mohammed S. Inayat, Ismail S. El-Amouri, Mohammad Bani-Ahmad, Howard L. Elford, Vincent S. Gallicchio, Oliver R. Oakley

Health and Clinical Sciences Faculty Publications

BACKGROUND: Graft-versus-host disease is the single most important obstacle facing successful allogeneic stem cell transplantation (SCT). Even with current immunosuppressive therapies, morbidity and mortality rates are high. Current therapies including cyclosporine A (CyA) and related compounds target IL-2 signaling. However, although these compounds offer great benefit, they are also associated with multiple toxicities. Therefore, new compounds with a greater efficacy and reduced toxicity are needed to enable us to overcome this hurdle.

METHODS: The allogeneic mixed lymphocyte reaction (MLR) is a unique ex vivo method to study a drug's action on the initial events resulting in T-cell activation and proliferation, …

White Matter Diffusion Alterations In Normal Women At Risk Of Alzheimer's Disease, Charles D. Smith, Himachandra Chebrolu, Anders H. Andersen, David A. Powell, Mark A. Lovell, Shuling Xiong, Brian T. Gold

Neurology Faculty Publications

Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal …

High-Throughput Experimental Studies To Identify Mirna Targets Directly, With Special Focus On The Mammalian Brain, Peter T. Nelson, Marianthi Kiriakidou, Zissimos Mourelatos, Grace S. Tan, Mary H. Jennings, Kevin Xie, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

We review the pertinent literature on methods used in high-throughput experimental identification of microRNA (miRNA) "targets" with emphasis on neurochemical studies. miRNAs are short regulatory noncoding RNAs that play important roles in the mammalian brain. The functions of miRNAs are related to their binding of RNAs including mRNAs. Since mammalian miRNAs tend to bind to target mRNAs via imperfect complementarity, understanding exactly which target mRNAs are recognized by which specific miRNAs is a challenge. Based on early experimental evidence, a set of "binding rules" for miRNAs has been described. These have focused on the 5' "seed" region of miRNAs binding …

Vampirism, Vampire Cults And The Teenager Of Today, Megan White, Hatim A. Omar

Pediatrics Faculty Publications

The aim of this paper is to summarize the limited literature on clinical vampirism, vampire cults and the involvement of adolescents in vampire-like behavior. The various definitions of clinical vampirism are outlined and the emergence of vampire cults from Gothic culture is examined. Further, the clinical features of cult behavior, the attraction to cults, the risk factors for cult involvement, and the clinical management of cult members are discussed. Additionally, vampire popular media is briefly introduced and a case study presented.

Organic Cation Transporter Preferentially Expressed In Hematopoietic Cells And Leukemias And Uses Thereof, Jeffrey A. Moscow, Xin Lu, Craig Jordan

Markey Cancer Center Faculty Patents

A novel organic cation transporter (OCT) gene, OCT 6, and use thereof is described. The OCT6 gene is preferentially expressed in human hematopoietic tissues, including CD34+ cells and leukemia cells. Its narrow tissue distribution, substrate specificity, and close homology to other cell membrane transporters make OCT6 an attractive target for the treatment of myeloid diseases.

Individual Micrornas (Mirnas) Display Distinct Mrna Targeting "Rules", Wang-Xia Wang, Bernard R. Wilfred, Kevin Xie, Mary H. Jennings, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) guide Argonaute (AGO)-containing microribonucleoprotein (miRNP) complexes to target mRNAs.It has been assumed that miRNAs behave similarly to each other with regard to mRNA target recognition. The usual assumptions, which are based on prior studies, are that miRNAs target preferentially sequences in the 3'UTR of mRNAs,guided by the 5' "seed" portion of the miRNAs. Here we isolated AGO- and miRNA-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with anti-AGO antibody. Cells were transfected with miR-107, miR-124,miR-128, miR-320, or a negative control miRNA. Co-IPed RNAs were subjected to downstream high-density Affymetrix Human Gene 1.0 ST microarray analyses using …

Rituximab In The Treatment Of B-Cell Non-Hodgkin Lymphoma, Focus On Outcomes And Comparative Effectiveness, Firas Badin, John Hayslip

Markey Cancer Center Faculty Publications

Rituximab is an important and well established component in the treatment of many patients with B-cell non-Hodgkin lymphoma. In this paper we review recent clinical trials investigating the addition of rituximab to standard chemotherapy regimens for treatment of patients with diffuse large B cell lymphoma and follicular lymphoma. This report focuses upon treatment efficacy, quality of life, and safety of rituximab or rituximab-containing regimens. More uniquely, we review economic aspects of lymphoma treatments, including the cost of standard chemotherapy regimens with or without rituximab, cost effectiveness of rituximab in both induction and maintenance treatment, and lymphoma's impacts on patient's productivity …

Omega-3 Fatty Acids: Potential Role In The Management Of Early Alzheimer's Disease, Gregory A. Jicha, William R. Markesbery

Sanders-Brown Center on Aging Faculty Publications

Omega-3 fatty acids are essential for brain growth and development. They play an important role throughout life, as critical modulators of neuronal function and regulation of oxidative stress mechanisms, in brain health and disease. Docosahexanoic acid (DHA), the major omega-3 fatty acid found in neurons, has taken on a central role as a target for therapeutic intervention in Alzheimer's disease (AD). A plethora of in vitro, animal model, and human data, gathered over the past decade, highlight the important role DHA may play in the development of a variety of neurological and psychiatric disorders, including AD. Cross sectional and prospective …

Microrna In Situ Hybridization In The Human Entorhinal And Transentorhinal Cortex, Peter T. Nelson, James Dimayuga, Bernard R. Wilfred

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) play key roles in gene expression regulation in both healthy and disease brains. To better understand those roles, it is necessary to characterize the miRNAs that are expressed in particular cell types under a range of conditions. In situ hybridization (ISH) can demonstrate cell- and lamina-specific patterns of miRNA expression that would be lost in tissue-level expression profiling. In the present study, ISH was performed with special focus on the human entorhinal cortex (EC) and transentorhinal cortex (TEC). The TEC is the area of the cerebral cortex that first develops neurofibrillary tangles in Alzheimer's disease (AD). However, the …

Anti-Argonaute Rip-Chip Shows That Mirna Transfections Alter Global Patterns Of Mrna Recruitment To Microribonucleoprotein Complexes, Wang-Xia Wang, Bernard R. Wilfred, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) play key roles in gene expression regulation by guiding Argonaute (AGO)-containing microribonucleoprotein (miRNP) effector complexes to target polynucleotides. There are still uncertainties about how miRNAs interact with mRNAs. Here we employed a biochemical approach to isolate AGO-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with a previously described anti-AGO antibody. Co-immunoprecipitated (co-IPed) RNAs were subjected to downstream Affymetrix Human Gene 1.0 ST microarray analysis. During rigorous validation, the "RIP-Chip" assay identified target mRNAs specifically associated with AGO complexes. RIP-Chip was performed after transfecting brain-enriched miRNAs (miR-107, miR-124, miR-128, and miR-320) and nonphysiologic control miRNA to identify …

A Comprehensive Approach To Obesity, Hypertension, And Mental Health Evaluation, Stefan G. Kiessling, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

The global epidemic of childhood and adolescent obesity in developing and developed countries has become a major public health concern. Given the relationship between obesity and hypertension as documented in several landmark studies, it is no surprise that, as the prevalence of obesity has increased in the pediatric population, rates of hypertension have also increased substantially. Hypertension is one of the most important risk factors for cardiovascular diseases and stroke; therefore, evaluation and initiation of appropriate treatment are extremely important in the pediatric population. Evaluation for secondary causes of hypertension, including renovascular, renoparenchymal, and endocrine disease, is the approach most …

Substance Abuse Among Adolescents, Abdel Salous, Hatim A. Omar

Pediatrics Faculty Publications

This chapter aims to provide a global perspective on substance abuse among adolescents across different cultures, and to review appropriate strategies in communicating with the adolescent population about substance abuse. Drug abuse continues to be a major public health issue in the United States, especially among adolescents. The attitude toward and involvement in drug abuse among adolescents is a complex problem shaped by multiple psychosocial parameters. Psychosocial variables such as ethnicity, and religion, and group dynamics, while deeply intertwined in shaping the cultural identity of adolescents, also deliver their impact to substance abuse in this patient population. In a society …

Hyperandrogenism And Obesity, Amit M. Deokar, Shawn J. Smith, Amanda J. Goodwin, Hatim A. Omar

Pediatrics Faculty Publications

This chapter has a two-fold objective. One, ti addresses the association of hyperandrogenism and obesity and the complex metabolic derangements that are part of the problem. Clinical management of these co-morbidities is challenging and complex. Second, this chapter will aid health care providers with the key features to an early diagnosis and intervention to decrease the morbidities in the short as well as long term. Method: Systematic review of articles and information on the topic of interest that were published in the last 15 years. Conclusion: Obesity and hyperandrogenism are integral parts of Metabolic Syndrome/Polycystic Ovarian Syndrome (PCOS)/Hyperandrogenism, Insulin resistance, …

Mir-107 Is Reduced In Alzheimer's Disease Brain Neocortex: Validation Study, Peter T. Nelson, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

MiR-107 is a microRNA (miRNA) that we reported previously to have decreased expression in the temporal cortical gray matter early in the progression of Alzheimer's disease (AD). Here we study a new group of well-characterized human temporal cortex samples (N=19). MiR-107 expression was assessed, normalized to miR-124 and let-7a. Correlation was observed between decreased miR-107 expression and increased neuritic plaque counts (P< 0.05) and neurofibrillary tangle counts (P< 0.02) in adjacent brain tissue. Adjusted miR-107 and BACE1 mRNA levels tended to correlate negatively (trend with regression P< 0.07). In sum, miR-107 expression tends to be lower relative to other miRNAs as AD progresses.

Parenting Adolescents, Sandra D'Angelo, Hatim A. Omar

Pediatrics Faculty Publications

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included.

A Policy And Intervention For Overweight Children And Adolescents, Kimberly K. Mcclanahan, Marlene B. Huff, Hatim A. Omar

Pediatrics Faculty Publications

The global epidemic of childhood and adolescent overweight has become a major public health concern. Not only are these youth more likely to become obese adults, and thus more prone to obesity-related diseases than their non overweight peers, they are also likely to suffer emotional and social effects associated with overweight. Overweight in youth has been linked to depression, low self-esteem, eating disorders, negative body image, and stigma. It appears to be bi-directional in nature, with overweight sometimes predicting certain psychological effects and psychosocial issues sometimes predicting overweight. Effective assessment and treatment of psychological and mental health issues in overweight …

Mental Health And Chronic Disease, Marlene B. Huff, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

By 2015, worldwide, 1.2 billion children aged 5-14 years will have some kind of significant chronic disease. Although scientific evidence indicates that children with chronic illness have more mental health issues than their healthy peers, many controversies and gaps in the literature exist. It is imperative that an understanding of the effects of chronic illness upon the mental health status of children and adolescents be undertaken. This chapter uses a biopsychosocial perspective to investigate the connection between chronic illness and mental health. The intent of the chapter is to suggest ways that medical and mental health professionals can provide services …

Youth Suicide Prevention In Rural Kentucky, Hatim A. Omar

Pediatrics Faculty Publications

Youth suicide continues to be one of the leading causes of death in the United States. Nation wide it is the third leading cause of death in the 10-24 year old age group. The rate of suicide varies somewhat from state to state. In the state of Kentucky, youth suicide is the second leading cause of death. This article describes a grass roots, community based program for youth suicide prevention and its impact on the community. The Stop Youth Suicide Campaign was launched in 2000 and included more than 30 local agencies. This program worked through public education, education of …

Pregnancy And Abortion, Shawn J. Smith, Amit M. Deokar, Hatim A. Omar

Pediatrics Faculty Publications

The role of caring for a pregnant adolescent can be rewarding, but it also possess unique challenges. A significant number of adolescent pregnancies are unintended and therefore providing comprehensive counseling is important even before the initiation of sexual activity. By understanding the risk factors the patient may further be provided delivery of appropriate health prevention/promotion services. It is also important for the health provider to continue to be an integral part of the life of the teenager and her child for an optimal development and growth.

The Female Athlete, Dilip R. Patel, Donald E. Greydanus, Hatim A. Omar

Pediatrics Faculty Publications

The female athlete has today became an accepted part of sports in elementary school, junior high, senior high, and college. This chapter covers various aspects of the prepubertal and pubertal female athlete. An historical perspective will be presented and selected comments provided on psychological and physiologic aspects of the female athlete. Concepts of adolescent gynecology are reviewed, including breast concerns and menstrual dilemmas in relation to sports activity. Exercise during pregnancy is also considered. Iron deficiency anemia and stress urinary incontinence

Radical Hysterectomy With Pelvic Lymphadenectomy: Indications, Technique, And Complications, Rachel A. Ware, John R. Van Nagell Jr.

Obstetrics and Gynecology Faculty Publications

Radical hysterectomy with pelvic lymphadenectomy remains the treatment of choice for women with Stages IA₂ and IB₁carcinoma of the cervix, and selected patients with Stage II endometrial cancer. Improvement in surgical techniqe, administration of prophylactic antibiotics, thromboemolic prophylaxis, and advances in critical care medicine have resulted in lower operative morbidity associated with this procedure. Major urinary tract complications such as ureteral injury or vesico-vaginal fistula are now extremely rare (< 1%). Five-year survival rates following this procedure vary according to a number of clinical and histologic variables, and may be as high as 90% in women without lymph node metastases.

Acute Musculoskeletal Sports Injury And Topical Nsaid, Amit M. Deokar, Shawn J. Smith, Hatim A. Omar

Pediatrics Faculty Publications

The objective of this chapter is to summarize the current standards of pain management in minor sports related musculoskeletal injuries. We also address the topical form of non-steroidal anti-inflammatory drug as an effective pain management option in an out-patient setting. Design: Quantitive systematic review of randomized controlled trials. Methods: The data was obtained through literature review of articles published in the last 10 years. In addition, FDA information on non-steroidal anti-inflammatory medications was also reviewed. The patient population studied in the articles included children and adults. Conclusion: Current standards of managing pain resulting from sports injuries involve a number of …

Down Syndrome And Sexuality, Maria José Carvalho Sant'anna, Bruna Marques Bononi, André Chao Vasconcellos De Oliveira, Tadeu Silveira Renattini, Carla Franchi Pinto, Maria Lucia Passarelli, Veronica Coates, Hatim A. Omar

Pediatrics Faculty Publications

In recent years important gains and changes have been observed in the life of teenagers with Down syndrome (DS) with increased inclusion into society. This chapter will discuss adolescence and sexuality in teenagers with DS from a descriptive study of 50 patients with DS between the ages of 10 and 20 years. The mean age was 13.5 years, 50% females. 86% went to school with 62.2% in school for over six years. Of the patients that attended school, 60% went to special education school and only 10% read and wrote correctly. In evaluation of autonomy, 66% took shower, 78% performed …

Chronic Illness And Mental Health Issues, Marlene B. Huff, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

By 2015, worldwide, 1.2 billion children aged 5-14 years will have some kind of significant chronic disease. Although scientific evidence indicates that children with chronic illness have more mental health issues than their healthy peers, many controversies and gaps in the literature exist. It is imperative that an understanding of the effects of chronic illness upon the mental health status of children and adolescent be undertaken. This article uses a biopsychosocial perspective to investigate the connection between chronic illness and mental health. The intent of the article is to suggest ways that medical and mental health professionals can provide services …

Educating Adolescents About Puberty: Are We Missing Something?, Hatim A. Omar

Pediatrics Faculty Publications

Adolescents undergo significant physical and cognitive changes during their pubertal development. These changes contribute to and impact their future development. Educating adolescents at an early age about their expected development decreases the possible anxiety associated with this period of life and also helps adolescents make better choices in regards to their sexuality. In order to assess the degree of education regarding pubertal development and sexuality, we conducted a survey of late adolescents (median age 19 years) and parents of adolescents. A total of 409 adolescents (237 females, 172 males) and 124 parents completed the survey. 14.4% of teens (36.6% of …

Mental Health Aspects Of An Adolescent Medicine Clinic Patient Population, Abdel Salous, Linah Al-Alem, Hatim A. Omar

Pediatrics Faculty Publications

The correlation between exposure to forms of violence and development of mental disorders in victims is well established. The purpose of this chapter was to identify mental health problems in an adolescent medicine clinic population in Lexington, KY and to investigate potential correlation of mental disorders with psychosocial factors. Data were gathered from the charts of 169 adolescent clinic patients (age 10-22) seen in the clinic for mental health care and analyzed using Excel. 68% of the patient population was urban, while 32% was rural. In terms of gender, 40% of the patients were male and 60% were female. 80% …

Quality Of Life And Adolescents In Rural Kentucky, Hatim A. Omar, Søren Ventegodt, Joav Merrick

Pediatrics Faculty Publications

In many rural areas in Kentucky, adolescents lack the basic assets for a good quality of life, such as having caring adults, a safe place and useful activities after school. In this chapter we analyze data from middle and high school students referred to a comprehensive school based health promotion center (SBHPC). From August 2006 to February 2008, a total of 382 students (200 female, 182 male, aged 12-18 years) were referred to the SBHPC for help. Only two (0.5%) students had two parents living with them and 12 (3.1 %) had safe, organized after school activities. 19.9% of the …

The Vampire Adolescent, Megan White, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

Quality Of Life And Persons With Intellectual Disability: Can We Measure Qol In This Population?, Søren Ventegodt, Hatim A. Omar, Flemming Struve, Tove K. Nielsen, Isack Kandel, Joav Merrick

Pediatrics Faculty Publications

Quality of life (QOL) has been discussed by professionals working with persons with intellectual disability (ID) for some time, but since QOL is concerned with subjective well-being, satisfaction and happiness, how is it possible to measure, when the person in question is unable to communicate? Consciousness is believed to be an internal and personal thing, but we have done the simple experiment to ask observers to rate QOL of another person, also in sub dimensions like self-assessed physical and mental health, relationship with self, self-assessed sexual ability, self-assessed social ability, and we have found that people are able to assess …