• 8-Cl-Adenosine enhances 1,25-dihydroxyvitamin D3-induced growth inhibition without affecting 1,25-dihydroxyvitamin D3-stimulated differentiation of primary mouse epidermal keratinocytes.

      Bollag, Wendy B; Zhong, Xiaofeng; Josephson, Sarah; Department of Medicine; Department of Cellular Biology and Anatomy; Institute of Molecular Medicine and Genetics (2004-08-10)
      BACKGROUND: Epidermal keratinocytes continuously proliferate and differentiate to form the mechanical and water permeability barrier that makes terrestrial life possible. In certain skin diseases, these processes become dysregulated, resulting in abnormal barrier formation. In particular, skin diseases such as psoriasis, actinic keratosis and basal and squamous cell carcinomas are characterized by hyperproliferation and aberrant or absent differentiation of epidermal keratinocytes. We previously demonstrated that 8-Cl-adenosine (8-Cl-Ado) can induce keratinocyte growth arrest without inducing differentiation. RESULTS: To determine if this agent might be useful in treating hyperproliferative skin disorders, we investigated whether 8-Cl-Ado could enhance the ability of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], a known keratinocyte differentiating agent and a clinical treatment for psoriasis, to inhibit keratinocyte growth. We found that low concentrations of 8-Cl-Ado and 1,25(OH)2D3 appeared to act additively to reduce proliferation of primary mouse epidermal keratinocytes. However, another agent (transforming growth factor-beta) that triggers growth arrest without inducing differentiation also coincidentally inhibits differentiation elicited by other agents; inhibition of differentiation is suboptimal for treating skin disorders, as differentiation is often already reduced. Thus, we determined whether 8-Cl-Ado also decreased keratinocyte differentiation induced by 1,25(OH)2D3, as measured using the early and late differentiation markers, keratin 1 protein levels and transglutaminase activity, respectively. 8-Cl-Ado did not affect 1,25(OH)2D3-stimulated keratin 1 protein expression or transglutaminase activity. CONCLUSIONS: Our results suggest that 8-Cl-Ado might be useful in combination with differentiating agents for the treatment of hyperproliferative disorders of the skin.
    • Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice

      Seto, Jong; Busse, Bjorn; Gupta, Himadri S.; Schafer, Cora; Krauss, Stefanie; Dunlop, John W. C.; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; et al. (2012-10-16)
      The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix - a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth.
    • Anomalous coronary artery found in the syncopal workup of an elderly man

      Oommen, Ronnie; Wilkins, Thad; Chen, Stephen Y; Arora, Vishal; Department of Family Medicine; Department of Medicine; Department of Cardiology (2012-07)
      Syncope, defined as a transient loss of consciousness, is seen in 1% of all visits to emergency departments and urgent care clinics in the United States. Syncope is categorized as cardiogenic, neurologic, or psychogenic. Anomalies of the coronary arteries are rare, and anomalous coronary arteries present as syncope more often in the young than in the elderly; syncope rarely occurs in patients 65 years of age and older. There are 2 major variants of coronary anomalies. In the first variant, the left main coronary artery arises from the right aortic sinus. In the second variant, the right coronary artery arises from the left aortic sinus. The risk of sudden death is higher in patients with the left coronary artery arising from the right aortic sinus. We present a case of an anomalous coronary artery discovered during the syncopal workup in a 66-year-old man because no such cases have been published in the United States. We will discuss the management of anomalous coronary arteries as well as a systematic approach to the diagnosis and management of syncope.
    • Association between Genetic Variants in DNA and Histone Methylation and Telomere Length

      Kim, Sangmi; Parks, Christine G.; Xu, Zongli; Carswell, Gleta; DeRoo, Lisa A.; Sandler, Dale P.; Taylor, Jack A.; Department of Medicine (2012-07-11)
      Telomere length, a biomarker of aging and age-related diseases, exhibits wide variation between individuals. Common genetic variation may explain some of the individual differences in telomere length. To date, however, only a few genetic variants have been identified in the previous genome-wide association studies. As emerging data suggest epigenetic regulation of telomere length, we investigated 72 single nucleotide polymorphisms (SNPs) in 46 genes that involve DNA and histone methylation as well as telomerase and telomere-binding proteins and DNA damage response. Genotyping and quantification of telomere length were performed in blood samples from 989 non-Hispanic white participants of the Sister Study, a prospective cohort of women aged 35–74 years. The association of each SNP with logarithmically-transformed relative telomere length was estimated using multivariate linear regression. Six SNPs were associated with relative telomere length in blood cells with p-values<0.05 (uncorrected for multiple comparisons). The minor alleles of BHMT rs3733890 G>A (p = 0.041), MTRR rs2966952 C>T (p = 0.002) and EHMT2 rs558702 G>A (p = 0.008) were associated with shorter telomeres, while minor alleles of ATM rs1801516 G>A (p = 0.031), MTR rs1805087 A>G (p = 0.038) and PRMT8 rs12299470 G>A (p = 0.019) were associated with longer telomeres. Five of these SNPs are located in genes coding for proteins involved in DNA and histone methylation. Our results are consistent with recent findings that chromatin structure is epigenetically regulated and may influence the genomic integrity of telomeric region and telomere length maintenance. Larger studies with greater coverage of the genes implicated in DNA methylation and histone modifications are warranted to replicate these findings.
    • Asymptomatic Severe Hypocalcemia Secondary to Vitamin D Deficiency in an Elderly Patient

      Aldasouqi, Saleh; Glassy, Crystal M.; Glassy, Matthew S.; Treska, Anxhela; Caldwell-McMillan, Molly; Gossain, Ved; Department of Medicine (2011-11-2)
    • Can novel Apo A-I polymorphisms be responsible for low HDL in South Asian immigrants?

      Dodani, Sunita; Dong, Yanbin; Zhu, Haidong; George, Varghese; Department of Medicine (2010-03-19)
      Coronary artery disease (CAD) is the leading cause of death in the world. Even though its rates have decreased worldwide over the past 30 years, event rates are still high in South Asians. South Asians are known to have low high-density lipoprotein (HDL) levels. The objective of this study was to identify Apolipoprotein A-I (Apo A-I) polymorphisms, the main protein component of HDL and explore its association with low HDL levels in South Asians. A pilot study on 30 South Asians was conducted and 12-h fasting samples for C-reactive protein, total cholesterol, HDL, low-density lipoprotein (LDL), triglycerides, Lipoprotein (a), Insulin, glucose levels, DNA extraction, and sequencing of Apo A-I gene were done. DNA sequencing revealed six novel Apo A-I single nucleotide polymorphisms (SNPs) in South Asians, one of which (rs 35293760, C938T) was significantly associated with low (<40 mg/dl) HDL levels (P = 0.004). The association was also seen with total cholesterol (P = 0.026) and LDL levels (P = 0.032). This pilot work has highlighted some of the gene-environment associations that could be responsible for low HDL and may be excess CAD in South Asians. Further larger studies are required to explore and uncover these associations that could be responsible for excess CAD risk in South Asians.
    • Carcinomatous Meningitis: The Natural History of Successfully Treated Metastatic Bladder Cancer

      Tadepalli, S.; Coleman, Teresa; Hackett, Ladawn A.; Liles, G.B.; Department of Medicine; Department of Pathology (2011-08-24)
      Carcinomatous meningitis due to bladder cancer is a rare entity reported only in case reports. Optimal therapy is thus poorly defined with earlier cases reporting an unsuccessful outcome. Here we report a case of late carcinomatous meningitis secondary to transitional cell carcinoma (TCC) of the bladder occurring in a patient in complete remission. He was successfully treated with intrathecal methotrexate and whole brain irradiation and experienced prolonged survival after treatment. With modern chemotherapy increasing complete remissions and survival rates in patients with TCC, more and more patients are being reported with carcinomatous meningitis. We raise the question of whether central nervous system prophylaxis should be considered in patients with TCC achieving a complete remission to chemotherapy in the metastatic setting.
    • Diagnosis and management of upper gastrointestinal bleeding.

      Wilkins, Thad; Khan, Naiman; Nabh, Akash; Schade, Robert R.; Department of Family Medicine; Department of Medicine (2012-03-01)
      Upper gastrointestinal bleeding causes significant morbidity and mortality in the United States, and has been associated with increasing nonsteroidal anti-inflammatory drug use and the high prevalence of Helicobacter pylori infection in patients with peptic ulcer bleeding. Rapid assessment and resuscitation should precede the diagnostic evaluation in unstable patients with severe bleeding. Risk stratification is based on clinical assessment and endoscopic findings. Early upper endoscopy (within 24 hours of presentation) is recommended in most patients because it confirms the diagnosis and allows for targeted endoscopic treatment, including epinephrine injection, thermocoagulation, application of clips, and banding. Endoscopic therapy results in reduced morbidity, hospital stays, risk of recurrent bleeding, and need for surgery. Although administration of proton pump inhibitors does not decrease mortality, risk of rebleeding, or need for surgery, it reduces stigmata of recent hemorrhage and the need for endoscopic therapy. Despite successful endoscopic therapy, rebleeding can occur in 10 to 20 percent of patients; a second attempt at endoscopic therapy is recommended in these patients. Arteriography with embolization or surgery may be needed if there is persistent and severe bleeding.
    • Excess coronary artery disease risk in South Asian immigrants: can dysfunctional high-density lipoprotein explain increased risk?

      Dodani, Sunita; Department of Medicine (2009-02-02)
      BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the United States (US), and South Asian immigrants (SAIs) have a higher risk of CAD compared to Caucasians. Traditional risk factors may not completely explain high risk, and some of the unknown risk factors need to be explored. This short review is mainly focused on the possible role of dysfunctional high-density lipoprotein (HDL) in causing CAD and presents an overview of available literature on dysfunctional HDL. DISCUSSION: The conventional risk factors, insulin resistance parameters, and metabolic syndrome, although important in predicting CAD risk, may not sufficiently predict risk in SAIs. HDL has antioxidant, antiinflammatory, and antithrombotic properties that contribute to its function as an antiatherogenic agent. Recent Caucasian studies have shown HDL is not only ineffective as an antioxidant but, paradoxically, appears to be prooxidant, and has been found to be associated with CAD. Several causes have been hypothesized for HDL to become dysfunctional, including Apo lipoprotein A-I (Apo A-I) polymorphisms. New risk factors and markers like dysfunctional HDL and genetic polymorphisms may be associated with CAD. CONCLUSIONS: More research is required in SAIs to explore associations with CAD and to enhance early detection and prevention of CAD in this high risk group.
    • Hydrogen peroxide improves the visibility of ulcer bases in acute non-variceal upper gastrointestinal bleeding: a single-center prospective study.

      Sridhar, Subbaramiah; Chamberlain, Sherman; Thiruvaiyaru, Dharma; Sethuraman, Sankara; Patel, Jigneshkumar; Schubert, Moonkyung; Cuartas-Hoyos, Francisco; Schade, Robert R.; Department of Medicine (2009-10-19)
      BACKGROUND: Acute non-variceal upper gastrointestinal bleeding (ANVB) or hemorrhage (used interchangeably) is an emergency. Endoscopically applied hydrogen peroxide (H2O2) has been shown to improve visualization of the ulcer base. AIMS: To test the hypothesis that ulcer base clot clearance with 3% H2O2 improves the visualization of ANVB lesions compared to water alone. METHODS: In this single-center prospective study, 320 patients with ANVB were examined, of which 81 met the entry criteria for evaluation. All patients with ANVB underwent urgent endoscopy. Those with adherent clots on the ulcer base were sprayed with 250 ml of water, followed by up to 100 ml of 3% H2O2. The main outcome measurement was Kalloo"s Visual Scores of the ulcer base before and after water and H2O2. RESULTS: Eighty-one patients with gastric ulcers (GU; 34) and duodenal ulcers (DU; 47) met the entry criteria. The mean improvement in grade from water to H2O2 was 2.04 (95% confidence interval [CI] (1.86, 2.23)). The mean volume of H2O2 used to clear clots was higher (70 ml) in patients who were negative for both Helicobacter pylori and non-steroidal anti-inflammatory drug (NSAID) use than in those who were positive for both (31 ml) (P = 0.00). More DU patients (72%) had visible vessels than GU patients (44%) (P = 0.01). CONCLUSIONS: H2O2 improved the visualization of ulcer bases in ANVB. A smaller volume of H2O2 was required to clear clots in patients who used NSAIDs and had H. pylori infection. H2O2 identified more DU vessels. The use of H2O2 should be considered as a standard therapy in the management of clots in ANVB.
    • Impact of clinical pharmacy services on renal transplant recipients' adherence and outcomes.

      Chisholm-Burns, Marie A; Spivey, Christina A; Garrett, Charlene; McGinty, Herbert; Mulloy, Laura L; Department of Medicine (2009-11-20)
      The purpose of this article is to provide a description of a clinical pharmacy services program implemented in a renal transplant clinic to improve medication access and adherence as well as health and economic outcomes among renal transplant recipients (RTRs). Following a team-based planning process and an informal survey of RTRs, a clinical pharmacy service intervention was implemented in the Medical College of Georgia renal transplant clinic. As part of the intervention, a clinical pharmacist reviewed and optimized medication therapy, provided instructions on how to take medication, and assisted with enrollment into medication assistance programs. Significant differences were found between RTRs who did and did not receive clinical pharmacy services on measures of adherence, health, economics, and quality of life. Clinical pharmacy services, as described in this article, have a positive impact on renal transplant recipients' medication adherence, health and economic outcomes, and health-related quality of life. The findings described here suggest that clinical pharmacy services are a viable and effective option for improving care for RTRs in an outpatient clinic setting.
    • Improved Immunodetection of Endogenous α-Synuclein

      Lee, Byung Rho; Kamitani, Tetsu; Department of Medicine; Center for Molecular Chaperone/Radiobiology & Cancer Virology (2011-08-19)
      α-Synuclein is a key molecule in understanding the pathogenesis of neurodegenerative α-synucleinopathies such as Parkinson's disease. Despite extensive research, however, its precise function remains unclear partly because of a difficulty in immunoblotting detection of endogenous α-synuclein. This difficulty has largely restricted the progress for α-synucleinopathy research. Here, we report that α-synuclein monomers tend to easily detach from blotted membranes, resulting in no or very poor detection. To prevent this detachment, a mild fixation of blotted membranes with paraformaldehyde was applied to the immunoblotting method. Amazingly, this fixation led to clear and strong detection of endogenous α-synuclein, which has been undetectable by a conventional immunoblotting method. Specifically, we were able to detect endogenous α-synuclein in various human cell lines, including SH-SY5Y, HEK293, HL60, HeLa, K562, A375, and Daoy, and a mouse cell line B16 as well as in several mouse tissues such as the spleen and kidney. Moreover, it should be noted that we could clearly detect endogenous α-synuclein phosphorylated at Ser-129 in several human cell lines. Thus, in some tissues and cultured cells, endogenous α-synuclein becomes easily detectable by simply fixing the blotted membranes. This improved immunoblotting method will allow us to detect previously undetectable endogenous α-synuclein, thereby facilitating α-synuclein research.
    • An Investigation of the Chronic Disease Self-Management Program - Assessing CDSMP Facilitators' Perceptions of the Program's Effect

      Hillman, L. M.; Anderson, C.; Stoodt, G.; Department of Medicine; Augusta University (2017-03)
      Chronic conditions are public health threats. The Chronic Disease Self-Management Program (CDSMP) is an evidence-based disease management program that addresses personal self-management of chronic conditions. The CDSMP involves peer trainers who instruct and assist with chronic disease preventive measures. Although disease management demonstrates promise to improving patient self-maintenance, previous researchers have not evaluated how the program affects program leaders. The purpose of this study was to discover how self-help leaders feel about the CDSM program. The overarching research question asked about perspectives that self-help leaders had toward the program. Through a narrative qualitative approach, the perceptions of peer leaders were examined to determine if the program was personally beneficial. Guided by the social cognitive theory, a purposeful convenience sample of 20 participants completed the study. The participants were practicing peer trainers in the CDSMP prog ram. Data analysis included hand coding using open and axial coding and content analysis. Study findings included themes surrounding how the CDSMP program benefits health in general as well as the management of facilitators’ own chronic diseases, health behaviors, and increased quality of life. The ability for chronic disease management leaders to experience positive effects of the program they administer may result in positive social change. This awareness can positively affect social change by enhancing an already established evidence-based community health program with stronger and better-equipped leaders.
    • Plerixafor Salvage Is Safe and Effective in Hard-to-Mobilize Patients Undergoing Chemotherapy and Filgrastim-Based Peripheral Blood Progenitor Cell Mobilization

      Awan, Farrukh T.; Kochuparambil, S. Thomas; DeRemer, David; Cumpston, Aaron; Craig, Michael; Jillella, Anand; Hamadani, Mehdi; Department of Medicine; Department of Pharmacology and Toxicology (2012-04-10)
      The combination of filgrastim (G-CSF) and plerixafor is currently approved for mobilizing peripheral blood progenitor cells in patients with non-Hodgkin lymphoma and multiple myeloma undergoing autologous peripheral blood hematopoietic cell transplantation. However, chemotherapy and G-CSF-based mobilization remains a widely used strategy for peripheral blood progenitor cell collection. In this paper we describe our experience from two North American transplant centers in a series of patients who received salvage plerixafor while failing chemotherapy and G-CSF mobilization. Patients received a median of two doses of plerixafor salvage upon failure to mobilize adequate number of peripheral blood progenitor cells at neutrophil recovery. The use of plerixafor was associated with a 2.4-fold increase in peripheral blood CD34+ cell count and 3.9-fold increase in total CD34+ cell yield. All patients were able to collect â ¥2 Ã 106 CD34+â cells/kg with this approach. These results were more pronounced in patients with a higher CD34+ cell count at the time of the first plerixafor dose. Interestingly, peripheral blood white blood cell count was not shown to correlate with a response to plerixafor. Our results provide safety and efficacy data for the use of plerixafor in patients who are destined to fail chemomobilization.
    • The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome.

      Pedersen-White, Jennifer R; Chorich, Lynn P; Bick, David P; Sherins, Richard J; Layman, Lawrence C; Department of Medicine; Department of Obstetrics and Gynecology; Department of Obstetrics and Gynecology; Institute of Molecular Medicine and Genetics; Institute of Neuroscience (2008-06-23)
      Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are clinically and genetically heterogeneous disorders caused by a deficiency of gonadotrophin-releasing hormone (GnRH). Mutations in three genes--KAL1, GNRHR and FGFR1--account for 15-20% of all causes of IHH/KS. Nearly all mutations are point mutations identified by traditional PCR-based DNA sequencing. The relatively new method of multiplex ligation-dependent probe amplification (MLPA) has been successful for detecting intragenic deletions in other genetic diseases. We hypothesized that MLPA would detect intragenic deletions in approximately 15-20% of our cohort of IHH/KS patients. Fifty-four IHH/KS patients were studied for KAL1 deletions and 100 were studied for an autosomal panel of FGFR1, GNRH1, GNRHR, GPR54 and NELF gene deletions. Of all male and female subjects screened, 4/54 (7.4%) had KAL1 deletions. If only anosmic males were considered, 4/33 (12.1%) had KAL1 deletions. No deletions were identified in any of the autosomal genes in 100 IHH/KS patients. We believe this to be the first study to use MLPA to identify intragenic deletions in IHH/KS patients. Our results indicate approximately 12% of KS males have KAL1 deletions, but intragenic deletions of the FGFR1, GNRH1, GNRHR, GPR54 and NELF genes are uncommon in IHH/KS.
    • PROTEIN SYNTHESIS IN PANCREAS OF FASTED PIGEONS

      Black, Owen; Webster, Paul D.; Department of Medicine; Department of Cellular Biology and Anatomy (1973-04-1)
      The regulation of protein synthesis in the pigeon has been studied by comparing the capability of cell-free amino acid incorporating systems of membrane-bound and membrane-free polysomes prepared from fasted and fed birds. New methods were developed for isolating polysomes since techniques used for other tissues did not provide quantitative recovery of polysomal RNA. The sucrose gradient profile of polysomes from pigeon pancreas showed a predominance of trisome species. Although initiation factors are present on polysomes, it was found that polysomes in cell-free systems would not initiate protein synthesis without exogenous initiation factors. This suggested the presence of an inhibitor or regulator of protein synthesis. These studies show that fasting resulted in: (a) decreased amounts of polysomes; (b) disaggregation of polysomes to monosomes; (c) decreased capability of polysomes to synthesize nascent peptides and to initiate additional synthesis, apparently not related to concentration of initiation factors.
    • Rab proteins in gastric parietal cells: evidence for the membrane recycling hypothesis.

      Calhoun, Benjamin C; Goldenring, J R; Department of Medicine (1997-07-08)
      The gastric parietal cell secretes large quantities of HCl into the lumen of the gastric gland in response to secretagogues such as histamine. In the membrane recycling hypothesis, this secretory activity requires the trafficking of the gastric H+/K(+)-ATPase to the cell surface from intracellular tubulovesicles. The Rab subclass of small GTP-binding proteins is thought to confer specificity to vesicle transport throughout the secretory pathway, and previous investigations established that Rab11 is highly expressed in gastric parietal cells. Recent discoveries in intra-Golgi transport and neuronal synaptic vesicle fusion have fortuitously converged on an evolutionarily conserved protein complex involved in vesicle docking and fusion. Recent results indicate that Rab11 is involved in the apical targeting of vesicles in parietal cells and other epithelial cells throughout the gastrointestinal tract. In support of the membrane recycling hypothesis, Rab co-segregates with H+/K(+)-ATPase in parietal cells. The presence of Rab11 on tubulovesicles supports a role for this Rab protein in recycling vesicle trafficking.
    • Rac1 Activation Driven by 14-3-3f Dimerization Promotes Prostate Cancer Cell-Matrix Interactions, Motility and Transendothelial Migration

      Goc, Anna; Abdalla, Maha; Al-Azayzih, Ahmad; Somanath, Payaningal R.; Department of Medicine (2012-07-13)
      14-3-3 proteins are ubiquitously expressed dimeric adaptor proteins that have emerged as key mediators of many cell signaling pathways in multiple cell types. Its effects are mainly mediated by binding to selective phosphoserine/threonine proteins. The importance of 14-3-3 proteins in cancer have only started to become apparent and its exact role in cancer progression as well as the mechanisms by which 14-3-3 proteins mediate cancer cell function remain unknown. While protein 14-3-3s is widely accepted as a tumor suppressor, 14-3-3f, b and c isoforms have been shown to have tumor promoting effects. Despite the importance of 14-3-3 family in mediating various cell processes, the exact role and mechanism of 14-3-3f remain unexplored. In the current study, we investigated the role of protein 14-3-3f in prostate cancer cell motility and transendothelial migration using biochemical, molecular biology and electric cell-substrate impedance sensing approaches as well as cell based functional assays. Our study indicated that expression with wild-type protein 14-3-3f significantly enhanced Rac activity in PC3 cells. In contrast, expression of dimer-resistant mutant of protein 14-3-3f (DM-14-3-3) inhibited Rac activity and associated phosphorylation of p21 activated kinase-1 and 2. Expression with wild-type 14-3-3f or constitutively active Rac1 enhanced extracellular matrix recognition, lamellipodia formation, cell migration and trans-endothelial migration by PC3 cells. In contrast, expression with DM 14-3-3f or DN-Rac1 in PC3 cells significantly inhibited these cell functions. Our results demonstrate for the first time that 14-3-3f enhances prostate cancer cell-matrix interactions, motility and transendothelial migration in vitro via activation of Rac1-GTPase and is an important target for therapeutic interventions for prostate cancer.
    • Symptomatic hypercalcemia in a patient with chronic tophaceous gout: a case report.

      Sachdeva, Alok; Goeckeritz, Bruce E; Oliver, Alyce M; Department of Medicine (2008-08-21)
      ABSTRACT: Hypercalcemia has been widely associated with granulomatous processes. This is due to enhanced extra-renal conversion of calcidiol to calcitriol by activated macrophages within the granuloma. Symptomatic hypercalcemia due to granulomatous disorders is not common, with the incidence in sarcoidosis ranging from 10-20%. Large aggregates of monosodium urate crystals in patients with longstanding chronic tophaceous gout can serve as the inciting antigen for the development of granuloma, but hypercalcemia has not been described in this context. We report a case of symptomatic hypercalcemia due to gouty tophi induced granulomatous inflammation. Long term treatment with immunosuppressants, in addition to bisphosphonates and uric acid lowering therapy, has led to stabilization of serum calcium levels and other lab parameters indicative of granulomatous burden.
    • An unusual case of peripartum cardiomyopathy manifesting with multiple thrombo-embolic phenomena.

      Ibebuogu, Uzoma N; Thornton, John W; Reed, Guy L; Department of Medicine (2007-12-31)
      ABSTRACT: Peripartum cardiomyopathy (PPCM) is a rare form of heart failure with a reported incidence of 1 per 3000 to 1 per 4000 live births and a fatality rate of 20%-50%. Onset is usually between the last month of pregnancy and up to 5 months postpartum in previously healthy women. Although viral, autoimmune and idiopathic factors may be contributory, its etiology remains unknown. PPCM initially presents with signs and symptoms of congestive heart failure and rarely with thrombo-embolic complications. We report an unusual case of PPCM in a previously healthy postpartum woman who presented with an acute abdomen due to unrecognized thromboemboli of the abdominal organs. This case illustrates that abdominal pain in PPCM may not always result from hepatic congestion as previously reported, but may occur as a result of thromboemboli to abdominal organs. Further research is needed to determine the true incidence of thromboemboli in PPCM.