Medicine and Health Sciences Commons^™

Activity Of Analogs Of Anticancer Drugs On The Serine Protease Enzymes Subtilisin And Chymotrypsin, Dhatri Ravipati

Masters Theses & Specialist Projects

The anticancer activity of several platinum compounds is due to the formation of complexes with DNA. We hypothesize that the size and shape of the platinum compounds would impact interaction with proteins, and these interactions may be partly responsible for the anticancer activity. Chymotrypsin and subtilisin are serine proteases that have a histidine residue in the active site. We are investigating the inhibition of the digestive enzymes chymotrypsin and subtilisin by analogs of the anticancer drug cisplatin and trying to discern trends in the inhibition as the active site residues vary. In our research, we found that the enzyme subtilisin …

Enforced Expression Of Tbx1 In Fetal Thymic Epithelial Cells Antagonizes Thymus Organogenesis, Kim T. Cardenas

Dissertations & Theses (Open Access)

Enforced expression of Tbx1 in fetal thymic epithelial cells antagonizes

thymus organogenesis

Kim T. Cardenas

The thymus and parathyroid glands originate from organ-specific domains of 3rd pharyngeal pouch (PP) endoderm. At embryonic day 11.5 (E11.5), the ventral thymus and dorsal parathyroid domains can be identified by Foxn1 and Gcm2 expression respectively. Neural crest cells, (NCCs) play a role in regulating patterning of 3rd PP endoderm. In addition, pharyngeal endoderm influences fate determination via secretion of Sonic hedgehog (Shh), a morphogen required for Gcm2 expression and generation of the parathyroid domain. Gcm2 is a downstream target of the transcription factor Tbx1, …

Immune And Hemorheological Changes In Chronic Fatigue Syndrome, Ekua W. Brenu, Donald R. Staines, Oguz K. Baskurt, Kevin J. Ashton, Sandra B. Ramos, Rhys M. Christy, Sonya M. Marshall-Gradisnik

Sonya Marshall-Gradisnik

Background - Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients. Methods - Flow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56dimCD16+ …

Immune And Hemorheological Changes In Chronic Fatigue Syndrome, Ekua W. Brenu, Donald R. Staines, Oguz K. Baskurt, Kevin J. Ashton, Sandra B. Ramos, Rhys M. Christy, Sonya M. Marshall-Gradisnik

Kevin Ashton

Background - Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients. Methods - Flow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56dimCD16+ …

Prevalence And Molecular Study Of G6pd Deficiency In Malaysian Orang Asli, Farahnaz Amini

Farahnaz Amini

This study aims to define the prevalence and the molecular basis of G6PD deficiency in the Negrito tribe of the Malaysian Orang Asli. Four hundred and eighty seven consenting Negrito volunteers were screened for G6PD deficiency through the use of a fluorescent spot test. DNA from deficient individuals underwent PCR-RFLP analysis using thirteen recognized G6PD mutations. In the instances when the mutation could not be identified by PCR-RFLP, the entire coding region of the G6PD gene was subjected to DNA sequencing. In total, 9% (44/486) of the sample were found to be G6PD-deficient. However, only 25 samples were subjected to …

Age-Associated Alterations In The F344xbn Rat Heart And The Efficacy Of Chronic Acetaminophen Ingestion As A Therapeutic Approach, Sunil K. Kakarla

Theses, Dissertations and Capstones

Despite advances in therapeutic and diagnostic strategies cardiovascular disease still remains the leading cause of death in older people. Recent studies suggest that age- related elevations in oxidative stress are associated with increases in cardiac apoptosis and compensatory hypertrophy of the remaining cardiomyocytes. Acetaminophen has been shown to exhibit cardioprotective effects following ischemia-reperfusion injury by acting as an antioxidant. Here, we investigate the molecular mechanisms underlying aging associated cardiac remodeling in male F344XBN rats and examine the efficacy of chronic acetaminophen ingestion as a therapeutic approach.

Aging in male F344XBN rats is characterized by a significant increase in heart size, …

Muscle Plasticity And Intramuscular Signaling In The Insulin-Resistant Obese Zucker Rat, Anjaiah Katta

Theses, Dissertations and Capstones

The ability to increase skeletal muscle mass may have important implications for the treatment of insulin resistance (IR) and diabetes [1-3]. Recent data suggest that IR muscle may adapt differently than normal muscle; however, molecular mechanism(s) responsible for this finding are not well understood [4]. Herein, we investigate the molecular mechanisms underlying the skeletal muscle remodeling in the IR Obese Zucker (OZ) rat.

The OZ rat is characterized by skeletal muscle insulin resistance, hyperglycemia, and hyperlipidemia. Compared to LZ rats, our data demonstrate that soleus muscle hypertrophy was significantly attenuated in the OZ rats after 3-weeks of muscle overload and …

Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin M. Rice, Bin Wang, Eric R. Blough

MIIR Faculty Research

Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, …

Biomimetic Precipitation Of Uniaxially Grown Calcium Phosphate Crystals From Full-Length Human Amelogenin Sols, Vuk Uskoković, Wu Li, Stefan Habelitz

Pharmacy Faculty Articles and Research

Human dental enamel forms over a period of 2 – 4 years by substituting the enamel matrix, a protein gel mostly composed of a single protein, amelogenin with fibrous apatite nanocrystals. Self-assembly of a dense amelogenin matrix is presumed to direct the growth of apatite fibers and their organization into bundles that eventually comprise the mature enamel, the hardest tissue in the mammalian body. This work aims to establish the physicochemical and biochemical conditions for the synthesis of fibrous apatite crystals under the control of a recombinant fulllength human amelogenin matrix in combination with a programmable titration system. The growth …

Hydrolysis Of Amelogenin By Matrix Metalloprotease-20 Accelerates Mineralization In Vitro, Vuk Uskoković, Feroz Khan, Haichuan Liu, Halina Ewa Witkowska, Li Zhu, Wu Li, Stefan Habelitz

Pharmacy Faculty Articles and Research

In the following respects, tooth enamel is a unique tissue in the mammalian body: (a) it is the most mineralized and hardest tissue in it comprising up to 95 wt% of apatite; (b) its microstructure is dominated by parallel rods composed of bundles of 40 – 60 nm wide apatite crystals with aspect ratios reaching up to 1:10,000 and (c) not only does the protein matrix that gives rise to enamel guides the crystal growth, but it also conducts its own degradation and removal in parallel. Hence, when mimicking the process of amelogenesis in vitro, crystal growth has to …

Altered Self-Assembly And Apatite Binding Of Amelogenin Induced By N-Terminal Proline Mutation, Li Zhu, Vuk Uskoković, Thuan Le, Pamela Denbesten, Yulei Huang, Stefan Habelitz, Wu Li

Pharmacy Faculty Articles and Research

Objective—A single Pro-70 to Thr (p.P70T) mutation of amelogenin is known to result in hypomineralized amelogenesis imperfecta (AI). This study aims to test the hypothesis that the given mutation affects the self-assembly of amelogenin molecules and impairs their ability to conduct the growth of apatite crystals.

Design—Recombinant human full-length wild-type (rh174) and p.P70T mutated amelogenins were analyzed using dynamic light scattering (DLS), protein quantification assay and atomic force microscopy (AFM) before and after the binding of amelogenins to hydroxyapatite crystals. The crystal growth modulated by both amelogenins in a dynamic titration system was observed using AFM.

Results—As …