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1.
Int Forum Allergy Rhinol ; 14(7): 1253-1257, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38343159

ABSTRACT

KEY POINT: Social determinants of health interactively influence sinonasal cancer care and prognosis. Housing-transportation and socioeconomic status showed the largest associations with disparities. The social vulnerability index can reveal the social determinants of sinonasal cancers.


Subject(s)
Paranasal Sinus Neoplasms , Humans , United States/epidemiology , Prognosis , Paranasal Sinus Neoplasms/epidemiology , Paranasal Sinus Neoplasms/therapy , Male , Female , Social Determinants of Health , Middle Aged , Aged , Social Class , Healthcare Disparities , Adult , Socioeconomic Factors , Vulnerable Populations/statistics & numerical data
3.
J Thromb Haemost ; 15(3): 473-476, 2017 03.
Article in English | MEDLINE | ID: mdl-27992120

ABSTRACT

Essentials Whether or not dabigatran enhances the risk of myocardial infarction is under discussion. We measured platelet reactivity and thrombin receptor expression in dabigatran patients. Platelet reactivity and thrombin receptor expression is enhanced during dabigatran treatment. This should be considered when choosing the optimal direct oral anticoagulant for individuals. SUMMARY: Background The direct oral anticoagulant (DOAC) dabigatran is a direct thrombin inhibitor. Its landmark trial, the RE-LY study, observed a trend towards a higher incidence of myocardial infarctions (MIs) in dabigatran-treated patients. Since then, there have been discussions on whether dabigatran increases the risk of MI. Objective In this study, we aimed to assess platelet reactivity and platelet thrombin receptor expression in dabigatran-treated patients. Methods We conducted a cross-sectional study in 13 hospitalized patients with planned initiation of dabigatran medication. Platelet reactivity was measured by light-transmission aggregometry and platelet thrombin receptor expression was measured by flow cytometry analysis. Results Platelet reactivity was higher after initiation of dabigatran medication as compared with baseline (baseline 44 ± 24% vs. dabigatran 70 ± 25%). Accordingly, the density of both platelet thrombin receptors (protease activated receptor [PAR]-1 and PAR-4) on platelets increased during dabigatran treatment (PAR1, baseline 63 ± 11% vs. dabigatran 70 ± 10%; PAR4, baseline 1.1 ± 0.5% vs. dabigatran 1.6 ± 0.9%). Conclusions Dabigatran increases platelet reactivity by enhancing the thrombin receptor density on platelets. This finding should be considered while choosing the optimal DOAC in individualized medicine.


Subject(s)
Atrial Fibrillation/metabolism , Blood Platelets/drug effects , Dabigatran/administration & dosage , Gene Expression Regulation , Receptors, Thrombin/metabolism , Administration, Oral , Aged , Anticoagulants/administration & dosage , Arachidonic Acid/chemistry , Blood Platelets/metabolism , Collagen/chemistry , Cross-Sectional Studies , Female , Flow Cytometry , Humans , Male , Middle Aged , Myocardial Infarction/drug therapy , Pilot Projects , Platelet Aggregation , Regression Analysis , Risk Factors , Thrombin/antagonists & inhibitors , Thrombin/metabolism
4.
J Am Pharm Assoc (2003) ; 54(3): 258-66, 2014.
Article in English | MEDLINE | ID: mdl-24816352

ABSTRACT

OBJECTIVE: To explore differences in perceived attributes of biometric screening services and organization characteristics among community pharmacies that adopt, outsource, or do not adopt biometric screening services that assess patients' blood pressure, blood glucose, serum cholesterol, and body mass index. DESIGN: Qualitative, comparative analysis. SETTING: Independently owned community pharmacies in Alabama. PARTICIPANTS: 25 key informants from community pharmacies were classified as adopters, outsourced adopters, and nonadopters of biometric screening services. Pharmacies using in-house staff to conduct screenings are referred to as adopters; those using external staff are referred to as outsourced adopters. MAIN OUTCOME MEASURES: Perceived attributes of the screening service and organizational characteristics identified through emergent theme analysis based on the Diffusion of Innovations Model and Model of Innovation Assimilation. RESULTS: The screening service was perceived differently by adopters, outsourced adopters, and nonadopters. Adopters saw the opportunity to increase revenue and expand the role of the pharmacist in health care by offering the service. Adopters also perceived the service to be compatible with their pharmacy layout and organizational identity; simple to implement; modifiable in terms of experimentation with models of service delivery; and visible by external constituencies (which positively affects pharmacy image). In contrast, nonadopters felt the amount of time, investment, and lack of potential patients associated with the service influenced their decision not to adopt it. Adopters and nonadopters differed in regard to their innovativeness in patient care services, their connectedness in professional networks, and how they make sense of and deal with the uncertainty of new programs. Outsourced adopters were similar to adopters but were more cautious in their decision making. CONCLUSION: Perceived attributes of the screening service and organizational characteristics differed among adopters, outsourced adopters, and nonadopters.


Subject(s)
Community Pharmacy Services , Delivery of Health Care/methods , Mass Screening/methods , Alabama , Diffusion of Innovation , Humans , Pharmacists , Qualitative Research
5.
Urology ; 83(5): 965-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24612616

ABSTRACT

Urologists and gynecologists manage most of the patients with female pelvic floor disorders. However, lack of a single focused approach among these two disciplines and other related fields may hinder advances in clinical care and research. Herein, along with describing the background of birth of the new subspeciality, we present a practical approach by which we established an integrated model of care and discovery for FPFD at our institution. With the recent approval of this subspeciality by the Accreditation Council for Graduate Medical Education (ACGME), it is plausible that other institutions would wish to initiate similar steps toward establishment of an integrated model of care for FPFD, and hence move this new subspecialty to its new frontiers.


Subject(s)
Gynecologic Surgical Procedures/history , Models, Organizational , Pelvic Floor Disorders/surgery , Urologic Surgical Procedures/history , Female , History, 20th Century , History, 21st Century , Humans , Interdisciplinary Communication , Patient Care Team/history , Patient Care Team/organization & administration
6.
Differentiation ; 80(2-3): 166-74, 2010.
Article in English | MEDLINE | ID: mdl-20427118

ABSTRACT

UNLABELLED: Liver stem cell (LSC) transplantation is a promising alternate approach to liver transplantation for patients with end-stage liver disease. However, the precise origin of LSCs remains unclear. Herein we determine if bone marrow mesenchymal stem cells (BMSCs) isolated from rats in acute hepatic failure (AHF) possess hepatic characteristics and have differentiation potential. BMSCs were isolated from AHF and sham-operated rats, and primary hepatocytes were isolated from normal rats for comparison. The transcriptomic profile of BMSCs and primary hepatocytes was analyzed using the Affymetrix GeneChip Rat Genome 230 2.0 Array. BMSCs isolated from AHF and normal rats were induced to differentiate into hepatocytes in vitro and the degree of hepatic differentiation was assessed using quantitative real time RT-PCR, immunohistochemistry, and biochemical assays. AHF-derived BMSCs had a significantly different gene expression profile compared to control BMSCs. Thirty-four gene/probe sets were expressed in both AHF-derived BMSCs and primary hepatocytes, but were absent in control-derived BMSCs, including 3 hepatocyte-specific genes. Forty-four genes were up-regulated more than 2-fold in AHF-derived BMSCs compared to controls, including 3 genes involved in hepatocyte metabolism and development. Furthermore, AHF-derived BMSCs expressed more hepatocyte related genes than control BMSCs. Additional experiments to validate the differentiation of AHF-derived BMSCs, compared to control-derived BMSCs, showed that several hepatocyte-specific genes and proteins [such as albumin (ALB) and alpha fetoprotein (AFP)] were expressed earlier, and at higher levels, after 1 week of differentiation. Hepatocyte-specific metabolic functions were also significantly higher in the AHF group compared to control cells. CONCLUSION: AHF-derived BMSCs had a hepatic transcriptional profile and expressed hepatocyte specific genes early during differentiation, and possessed greater hepatogenic potency in vitro compared to cells isolated from control animals, further confirming their potential as a stem cell-based therapy for end-stage liver disease.


Subject(s)
Gene Expression Profiling , Hematopoietic Stem Cells/cytology , Hepatocytes/cytology , Liver Failure/pathology , Mesenchymal Stem Cells/cytology , Transcription, Genetic , Acute Disease , Animals , Cell Differentiation , Flow Cytometry , Oligonucleotide Array Sequence Analysis , Rats
7.
Stem Cells Dev ; 19(9): 1427-36, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20055663

ABSTRACT

UNLABELLED: Liver tissue engineering with hepatic stem cells provides a promising alternative to liver transplantation in patients with acute and chronic hepatic failure. In this study, a three-dimensional (3D) bioscaffold was introduced for differentiation of rat bone marrow mesenchymal stem cells (BMSCs) into hepatocytes. For hepatocyte differentiation, third passage BMSCs isolated from normal adult F344 rats were seeded into collagen-coated poly(lactic-co-glycolic acid) (C-PLGA) 3D scaffolds with hepatocyte differentiation medium for 3 weeks. Hepatogenesis in scaffolds was characterized by reverse transcript PCR, western blot, confocal laser scanning microscopy (CLSM), periodic acid-Schiff staining, histochemistry, and biochemical assays with hepatic-specific genes and markers. A monolayer culture system was used as a control differentiation group. The results showed that isolated cells possessed the basic features of BMSCs. Differentiated hepatocyte-like cells in C-PLGA scaffolds expressed hepatocyte-specific markers [eg, albumin (ALB), alpha-fetoprotein, cytokeratin 18, hepatocyte nuclear factor 4alpha, and cytochrome P450] at mRNA and protein levels. Most markers were expressed in C-PLGA group 1 week earlier than in the control group. Results of biocompatibility indicated that the differentiated hepatocyte-like cells grew more stably in C-PLGA scaffolds than that in controls during a 3-week differentiation period. The significantly higher metabolic functions in hepatocyte-like cells in the C-PLGA scaffold group further demonstrated the important role of the scaffold. CONCLUSION: As the phenomenon of transdifferentiation is uncommon, our successful transdifferentiation rates of BMSCs to mature hepatocytes prove the superiority of the C-PLGA scaffold in providing a suitable environment for such a differentiation. This material can possibly be used as a bioscaffold for liver tissue engineering in future clinical therapeutic applications.


Subject(s)
Bone Marrow Cells/drug effects , Cell Differentiation/drug effects , Hepatocytes/drug effects , Lactic Acid/pharmacology , Mesenchymal Stem Cells/drug effects , Polyglycolic Acid/pharmacology , Tissue Scaffolds , Animals , Bone Marrow Cells/physiology , Cell Culture Techniques , Cell Survival , Cells, Cultured , Hepatocytes/metabolism , Hepatocytes/physiology , Lactic Acid/chemistry , Liver Function Tests , Materials Testing , Mesenchymal Stem Cells/physiology , Phenotype , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Rats , Rats, Inbred F344 , Tissue Scaffolds/chemistry
8.
Obesity (Silver Spring) ; 18(1): 161-6, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19521346

ABSTRACT

We examined 11-year (1997-2007) trends in underweight, overweight, and obesity in Greek children. Population data derived from a yearly, school-based health survey carried out between 1997 and 2007 in >80% of all Greek schools. Height and weight measurements from 651,582 children, aged 8-9 years (boys: 51.2%) were analyzed. The gender- and age-specific BMI cutoff points by the International Obesity Task Force (IOTF) were used in order to define underweight, normal weight, overweight, and obesity. Trend analysis showed an increase in the prevalence of obesity from 7.2 +/- 0.2% in 1997 to 11.3 +/- 0.2% in 2004 for girls (P < 0.001) and from 8.1 +/- 0.2% in 1997 to 12.3 +/- 0.2% in 2004 for boys (P < 0.001). An apparent leveling off in obesity rates was observed during 2004-2007 for both boys and girls. The prevalence of overweight rose between 1997 and 2007 from 20.2 +/- 0.2% to 26.7 +/- 0.2% for girls (P < 0.001) and from 19.6 +/- 0.2% to 26.5 +/- 0.2% for boys (P < 0.001). The overall prevalence of thinness in the same period remained constant in both sexes. The presented population-based data revealed that the prevalence of overweight and obesity among 8- to 9-year-old Greek children is alarmingly elevated, with the overweight rates rising continuously. However, an apparent leveling off in obesity rates for the past 4 consecutive years was documented for the first time in both genders.


Subject(s)
Health Status , Health Surveys , Obesity/epidemiology , Overweight/epidemiology , Anthropometry , Body Mass Index , Chi-Square Distribution , Child , Female , Greece/epidemiology , Humans , Male , Prevalence , Regression Analysis
9.
J Appl Psychol ; 94(5): 1354-64, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19702377

ABSTRACT

This study investigated participants' reactions to employee testimonials presented on recruitment Web sites. The authors manipulated the presence of employee testimonials, richness of media communicating testimonials (video with audio vs. picture with text), and representation of racial minorities in employee testimonials. Participants were more attracted to organizations and perceived information as more credible when testimonials were included on recruitment Web sites. Testimonials delivered via video with audio had higher attractiveness and information credibility ratings than those given via picture with text. Results also showed that Blacks responded more favorably, whereas Whites responded more negatively, to the recruiting organization as the proportion of minorities shown giving testimonials on the recruitment Web site increased. However, post hoc analyses revealed that use of a richer medium (video with audio vs. picture with text) to communicate employee testimonials tended to attenuate these racial effects.


Subject(s)
Audiovisual Aids , Internet , Personnel Selection/methods , Persuasive Communication , Adult , Black or African American/psychology , Attitude , Cultural Diversity , Female , Humans , Male , Multivariate Analysis , United States , White People/psychology
10.
Stem Cells Dev ; 17(1): 143-55, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18225978

ABSTRACT

Previous studies have shown that bone marrow beta 2m(-)/Thy-1+ hepatic stem cells (BMHSCs) were able to engraft in vivo and differentiate into functioning hepatocytes in vitro. Our transcriptomic profiling on BMHSCs derived from rats subjected to common bile duct ligation (CBDL) demonstrated CBDL-derived beta 2m(-)/Thy-1+ BMHSCs expressed hepatocyte-like genes and shared more commonly expressed genes with hepatocytes, suggesting that an "on-site" priming of BMHSCs into hepatocyte lineage was initiated under the condition of CBDL. In this paper, transcriptomic profiling was carried out on livers from rats with CBDL to identify candidate factors released from cholestatic livers possibly involved in the priming of BMHSCs using Affymetrix Rat Genome U34A arrays. In CBDL rat livers, 1,091 probe sets were differentially expressed, of which 188 up-regulated probe sets were annotated as "extracellular" components. Gene ontology analysis showed many up-regulated genes belonged to cytokines, chemokines and growth factors, including Il1b, Il18, Ptn, Spp1, Grn, Ccl2, Cxcl1, Pf4, Tgfb, and Tgfb3. Cell differentiation and proliferation regulation factors such as Dmbt1, Efna1, Lgals1, Lep, Pmp2, and Gas6 were also induced in CBDL livers. Furthermore, many proteolysis and peptidolysis genes such as Mmp2, Mmp12, Mmp14, and Mmp23 were up-regulated in CBDL livers. Gene expression profiling showed that many cytokine-, chemokine-, growth factor- as well as certain extracellular protein-related genes were induced in CBDL livers, suggesting that these genes may be involved in hepatic BMHSCs priming.


Subject(s)
Bone Marrow , Cholestasis/metabolism , Hepatocytes/cytology , Liver/cytology , Liver/metabolism , Stem Cells/cytology , Animals , Cell Differentiation , Cell Proliferation , Chemokines/genetics , Cytokines/genetics , Gene Expression Profiling , Intercellular Signaling Peptides and Proteins/genetics , Rats , Up-Regulation
11.
J Endovasc Ther ; 14(4): 544-50, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17696631

ABSTRACT

PURPOSE: To evaluate coronary flow reserve (CFR) changes following stent implantation in the descending thoracic aorta (DTA) of a porcine model. METHODS: Six pigs (3 males; 40 to 44 kg) were anesthetized and kept on mechanical ventilation. A 6-F guiding right Judkins catheter was advanced under fluoroscopy to the right coronary artery, and a pressure wire with a temperature sensor was placed within the vessel lumen at a distance of 4 cm from the ostium. CFR was estimated by the thermodilution method before and after maximal coronary vasodilation with 20 mg of intracoronary papaverine. Aortography was also performed to measure aortic diameter. Subsequently, a self-expanding vascular stent was deployed into the DTA just below the left subclavian artery (LSA), and CFR was measured again. All animals were maintained for 3 weeks; at the end of this period, a further CFR was calculated using the same procedure. RESULTS: The mean aortic diameter below the LSA was 12.15+/-0.15 mm. Following stent deployment, the mean aortic diameter measured at the stented segment was 12.58+/-0.11 (p=0.001 versus baseline). The mean CFR value was 4.70+/-2.00 before stent implantation, 2.68+/-0.86 immediately after, and 4.05+/-1.15 at 3 weeks after stenting. Accordingly, CFR values were significantly depressed immediately after stent placement compared with baseline (p=0.027). However, CFR values obtained 3 weeks following stent deployment were similar to the initial values (p=0.59). CONCLUSION: Stent deployment in the normal swine DTA produces a significant immediate decrease in CFR, which is attenuated 3 weeks later. The clinical impact of CFR changes following DTA endografting remain to be elucidated.


Subject(s)
Aorta, Thoracic/surgery , Coronary Circulation , Stents , Vascular Surgical Procedures/instrumentation , Animals , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/physiopathology , Aortography , Cardiovascular Agents/pharmacology , Compliance , Coronary Circulation/drug effects , Female , Male , Models, Animal , Papaverine/pharmacology , Regional Blood Flow , Research Design , Swine , Thermodilution , Time Factors
12.
Korean J Intern Med ; 22(2): 93-100, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17616024

ABSTRACT

BACKGROUND: Distinguishing those patients with fulminant hepatic failure (FHF) and who require transplantation from those FHF patients who will survive with receiving only intensive medical care remains problematic, and this distinction is important because of the chronic shortage of donor livers. METHODS: To assess the applicability of two prognostic scoring systems, referred to as the London and Clichy criteria, we compared using both systems, at the time of admission, for 43 FHF patients (15 M/28 F; age: 3716 yrs). Acetaminophen (ACM) was the etiology for 16 patients, while the remaining 27 had other etiologies. All the patients received intensive care, and 18 (8 ACM/10 non-ACM) had investigational BAL support. RESULTS: For the ACM toxicity, neither the London nor the Clichy criteria exhibited acceptable sensitivity (71 vs 86%, respectively), specificity (78 vs 56%, respectively), a positive predictive value (71 vs 60%, respectively), a negative predictive value (78 vs 83%, respectively) or predictive accuracy (75 vs 69%, respectively) to predict patient survival without transplantation. In contrast, applying the London and Clichy criteria to the FHF patients with non-ACM etiologies showed a sensitivity of 96 vs 80%, respectively, a specificity of 100 vs 100%, respectively, a positive predictive value of 100 vs 100%, respectively a negative predictive value of 67 vs 29%, respectively and a predictive accuracy of 96% vs 82%, respectively. CONCLUSIONS: Overall, the London criteria more accurately predicted the need for transplantation, and neither the London criteria nor the Clichy prognostic criteria accurately predicted the outcome of those patients who suffered with FHF due to ACM. BAL support may have contributed to the survival of the patients with ACM toxicity and who didn't undergo transplantation, and this survival exceeded the predictions of both prognostic systems. Additional multicenter studies should be conducted to refine these prognostic scoring systems, and this will help physicians rapidly identify those FHF patients who can survive without undergoing liver transplantation.


Subject(s)
Liver Failure, Acute/diagnosis , Liver Transplantation , Severity of Illness Index , Survival Analysis , Adolescent , Adult , Aged , Child , Female , Humans , Liver Failure, Acute/mortality , Liver Failure, Acute/surgery , Male , Middle Aged , Outcome Assessment, Health Care , Prognosis , Risk Assessment , Sensitivity and Specificity
13.
Article in English | WPRIM (Western Pacific) | ID: wpr-24293

ABSTRACT

BACKGROUND: Distinguishing those patients with fulminant hepatic failure (FHF) and who require transplantation from those FHF patients who will survive with receiving only intensive medical care remains problematic, and this distinction is important because of the chronic shortage of donor livers. METHODS: To assess the applicability of two prognostic scoring systems, referred to as the London and Clichy criteria, we compared using both systems, at the time of admission, for 43 FHF patients (15 M/28 F; age: 3716 yrs). Acetaminophen (ACM) was the etiology for 16 patients, while the remaining 27 had other etiologies. All the patients received intensive care, and 18 (8 ACM/10 non-ACM) had investigational BAL support. RESULTS: For the ACM toxicity, neither the London nor the Clichy criteria exhibited acceptable sensitivity (71 vs 86%, respectively), specificity (78 vs 56%, respectively), a positive predictive value (71 vs 60%, respectively), a negative predictive value (78 vs 83%, respectively) or predictive accuracy (75 vs 69%, respectively) to predict patient survival without transplantation. In contrast, applying the London and Clichy criteria to the FHF patients with non-ACM etiologies showed a sensitivity of 96 vs 80%, respectively, a specificity of 100 vs 100%, respectively, a positive predictive value of 100 vs 100%,, respectively a negative predictive value of 67 vs 29%, respectively and a predictive accuracy of 96% vs 82%, respectively. CONCLUSIONS: Overall, the London criteria more accurately predicted the need for transplantation, and neither the London criteria nor the Clichy prognostic criteria accurately predicted the outcome of those patients who suffered with FHF due to ACM. BAL support may have contributed to the survival of the patients with ACM toxicity and who didn't undergo transplantation, and this survival exceeded the predictions of both prognostic systems. Additional multicenter studies should be conducted to refine these prognostic scoring systems, and this will help physicians rapidly identify those FHF patients who can survive without undergoing liver transplantation.


Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Liver Failure, Acute/diagnosis , Liver Transplantation , Outcome Assessment, Health Care , Prognosis , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Survival Analysis
14.
Ther Apher Dial ; 10(2): 138-44, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16684215

ABSTRACT

There is a need to develop artificial means of liver replacement and/or assistance with the aim of either supporting patients with borderline functional liver cell mass until their liver regenerates, or until a donor liver becomes available for transplantation. Selective plasma filtration is a novel approach to blood purification therapy designed to reduce the level of circulating toxins of hepatic and renal failure, mediators of inflammation and inhibitors of hepatic regeneration. The results of preclinical studies indicate that treatment of pigs with experimentally-induced fulminant hepatic failure is safe and effective in extending survival time and arresting brain swelling. In addition, the amount of ammonia, aromatic amino acids, IL6, TNFalpha and C3a removed during the 6-h treatment in the present study was higher by 34% to 175% than the total plasma content of those substances at the start of therapy.


Subject(s)
Hemofiltration/instrumentation , Liver Failure, Acute/therapy , Animals , Blood Chemical Analysis , Equipment Design , Female , Statistics, Nonparametric , Survival Analysis , Swine
15.
J Appl Psychol ; 91(2): 467-474, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16551197

ABSTRACT

The authors explored the idea that teams consisting of members who, on average, demonstrate greater mastery of relevant teamwork knowledge will demonstrate greater task proficiency and observed teamwork effectiveness. In particular, the authors posited that team members' mastery of designated teamwork knowledge predicts better team task proficiency and higher observer ratings of effective teamwork, even while controlling for team task proficiency. The authors investigated these hypotheses by developing a structural model and testing it with field data from 92 teams (1,158 team members) in a United States Air Force officer development program focusing on a transportable set of teamwork competencies. The authors obtained proficiency scores on 3 different types of team tasks as well as ratings of effective teamwork from observers. The empirical model supported the authors' hypotheses.


Subject(s)
Cognition , Cooperative Behavior , Employee Performance Appraisal , Organizational Culture , Professional Competence , Workplace/psychology , Humans , Surveys and Questionnaires
16.
Cell Transplant ; 14(6): 391-6, 2005.
Article in English | MEDLINE | ID: mdl-16180657

ABSTRACT

Hepatocyte transplantation and use of bioartificial liver support systems have been suggested as potential therapies for fulminant hepatic failure. Cryopreservation in liquid nitrogen is presently the major method of long-term storage of isolated hepatocytes. However, cryopreservation can result in low cell recovery and reduction in differentiated function. Several possible mechanisms of cell death during cryopreservation have been proposed. The most important mechanisms appear to be oxidative stress and apoptosis. In this study, we isolated fresh rat hepatocytes and cryopreserved them in three media: University of Wisconsin (UW) solution, an antioxidant-containing medium, and medium containing a caspase inhibitor. Viability and function of hepatocytes cryopreserved in these media were examined. Cryopreservation conditions had no effect on hepatocyte viability after thawing. However, after culture we found significant improvements in viability and function in both antioxidant- and caspase inhibitor-treated hepatocytes at 6 and 24 h.


Subject(s)
Antioxidants/pharmacology , Caspase Inhibitors , Cryopreservation , Hepatocytes/enzymology , Protease Inhibitors/pharmacology , Animals , Apoptosis/drug effects , Caspases/metabolism , Cells, Cultured , Cryopreservation/methods , Culture Media , Hepatocytes/cytology , Liver, Artificial , Male , Oxidative Stress/drug effects , Rats
17.
Cell Transplant ; 14(6): 411-21, 2005.
Article in English | MEDLINE | ID: mdl-16180660

ABSTRACT

Pancreatic islet transplantation is limited by shortage of donor organs. Although beta-cell lines could be used, their secretion of insulin is characteristically glucose independent and immunoisolation is required. Here we show that intrasplenic transplantation of encapsulated glucose-responsive mouse insulinoma cells reversed streptozotocin (STZ)-induced diabetes in rats. MIN-6 cells derived from a transgenic mouse expressing SV 40 large T antigen in pancreatic beta-cells were transfected with minigene encoding for human glucagon-like-peptide-1 under the control of rat insulin promoter. The cells were encapsulated in alginate/poly-L-lysine and used for cell transplantation in STZ-diabetic rats. Rats with nonfasting blood glucose (n-FBG) greater than 350 mg/dl were used. In group I rats (n=6) 20 million encapsulated cells were injected into the spleen. Group II rats (n=6) received empty capsules. n-FBG was measured biweekly. After 4 and 8 weeks, an intraperitoneal glucose tolerance test (IPGTT) was performed in group I; normal rats served as controls. Plasma insulin level was measured every other week (RIA). After 8 weeks, spleens were removed 1 day before sacrifice. In rats transplanted with cells the n-FBG was 100-150 mg/dl until the end of the study. After splenectomy, all cell recipients became diabetic (glucose 400 +/- 20 mg/dl). Transplanted rats showed increase in body weight and insulin production (3.3 +/- 1.0 ng/ml versus 0.92 +/- 0.3 ng/ml; p < 0.01) and had normal IPGTT. Spleens contained capsules with insulin-positive cells. Overall, data from this work indicate that intrasplenic transplantation of xenogeneic encapsulated insulin-producing cells without immunosuppression reversed diabetes in rats. Excellent survival and function of the transplanted cells was due to the fact that the cells were separated from the bloodstream by the immunoisolatory membrane only and insulin was delivered directly to the liver (i.e., in a physiological manner).


Subject(s)
Diabetes Mellitus, Experimental/therapy , Insulinoma/metabolism , Spleen , Transplants , Animals , Blood Glucose/analysis , Cells, Immobilized/transplantation , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Humans , Insulin/blood , Male , Mice , Mice, Transgenic , Neoplasm Transplantation/methods , Promoter Regions, Genetic/genetics , Rats , Rats, Wistar , Spleen/metabolism , Streptozocin/toxicity
18.
J Surg Res ; 129(1): 142-6, 2005 Nov.
Article in English | MEDLINE | ID: mdl-15936773

ABSTRACT

BACKGROUND: Pituitary tumor transforming gene (PTTG), homologous to a mammalian securin, plays a pivotal role in cell transformation, however, its biological function(s) in normal tissues is not fully understood. Because the liver is a regenerative organ, the relevant biological function of PTTG in the liver would be more feasible to understand PTTG. Also, PTTG may be involved in the liver regeneration. MATERIALS AND METHODS: Expressions of rat hepatic PTTG messengerRNA (mRNA) and cellular immunoreactivities during the cell proliferative period of the liver regeneration both in vitro and in vivo were tested. RESULTS: PTTG expression of the rat primary hepatocyte was stimulated by HGF in a dose dependent manner, and was suppressed when hepatocyte proliferation was inhibited by transforming growth factor-beta1. A positive PTTG immunoreactive co-localizing with 5-bromo-2'-deoxyuridine (BrdU) in the hepatocyte nucleus was found and there was a concurrent sister chromatin itself by the immunofluorescent labeling of PTTG with cytokeratin 18 (CK18). DISCUSSION: Since the correlation of PTTG mRNA expression, cell proliferation and immunoreactivity were observed in primary rat cultured hepatocytes, PTTG may be a novel marker of cell proliferation both in vitro and in vivo liver regeneration.


Subject(s)
Liver Regeneration/genetics , Neoplasm Proteins/genetics , Animals , Biomarkers , Bromodeoxyuridine/analysis , Cell Division/drug effects , Cell Nucleus/chemistry , Cells, Cultured , Fluorescent Antibody Technique , Fluorescent Dyes , Gene Expression/drug effects , Hepatectomy , Hepatocyte Growth Factor/pharmacology , Hepatocytes/drug effects , Hepatocytes/metabolism , Hepatocytes/ultrastructure , Immunohistochemistry , Keratins/analysis , Neoplasm Proteins/analysis , RNA, Messenger/analysis , Rats , Securin , Transforming Growth Factor beta/pharmacology , Transforming Growth Factor beta1
19.
Transplantation ; 79(7): 783-90, 2005 Apr 15.
Article in English | MEDLINE | ID: mdl-15818320

ABSTRACT

BACKGROUND: Encapsulated cell therapy might be a promising approach to enable cell transplantation without immunosuppression. This study investigates the viability and hepatic function of hepatocytes encapsulated with alginate/poly-L-lysine in vitro and the effect of the intrasplenic transplantation of cultured encapsulated hepatocytes on survival in 90% hepatectomized rats as a preliminary step toward allogeneic hepatocyte transplantation without immunosuppression. MATERIALS AND METHODS: Rat hepatocytes were isolated and encapsulated using alginate/poly-L-lysine. Encapsulated hepatocytes were cultured for 28 days to measure cell viability, liver function, and morphology. Rats were treated with a 90% partial hepatectomy and then immediately underwent the intrasplenic transplantation of the cultured encapsulated hepatocytes, the capsule alone, or the allogeneic hepatocytes without the capsule. The survival rate, liver function, and cell morphology were assessed after transplantation. RESULTS: The cultured encapsulated hepatocytes maintained their viability and showed better metabolic activity than day 0 cultured encapsulated hepatocytes. The encapsulated cells strongly expressed albumin and were positive for periodic acid-Schiff staining. Electron microscopy demonstrated that the microencapsulated hepatocytes retained the structural elements of hepatic cytoplasm and nuclei. Intrasplenic transplantation of the encapsulated hepatocytes increased the survival rate and improved the hepatic function. Encapsulated hepatocytes transplanted into rat spleen survived well and retained their hepatic function. Moreover, dramatic liver regeneration was observed 48 hr after transplantation in the group that received intrasplenic transplantations of encapsulated hepatocytes. CONCLUSIONS: The intrasplenic transplantation of cultured encapsulated hepatocytes improved the survival rate of an acute liver failure rat model induced by a 90% partial hepatectomy.


Subject(s)
Hepatocytes/transplantation , Liver Failure, Acute/physiopathology , Spleen , Animals , Cell Survival , Cells, Cultured , Hepatectomy , Hepatocytes/cytology , Hepatocytes/ultrastructure , Liver Failure, Acute/pathology , Liver Regeneration , Microscopy, Electron, Transmission , Organ Size , Rats , Rats, Inbred Lew , Survival Rate , Transplantation, Homologous
20.
Biochem Biophys Res Commun ; 327(1): 252-60, 2005 Feb 04.
Article in English | MEDLINE | ID: mdl-15629456

ABSTRACT

The aim of the present study was to determine if the bone marrow (BM) beta2m-/Thy-1+ stem cells isolated from common bile duct ligated (CBDL) rats possess hepatocyte-like characteristics in their global gene expression profiles. The Affymetrix RG U34A arrays were used to conduct transcriptomic profiling on BM beta2m-/Thy-1+ stem cells isolated from CBDL and control rats as well as primary hepatocytes. Forty-one probe sets were up-regulated more than 2-fold in CBDL-derived beta2m-/Thy-1+ BM stem cells compared to control BM stem cells. Twenty-seven probe sets were present in both CBDL-derived beta2m-/Thy-1+ BM stem cells and control hepatocytes but absent in control beta2m-/Thy-1+ BM stem cells, including Tcf1 and Dbp. Compared to the control beta2m-/Thy-1+ BM stem cells, CBDL-derived beta2m-/Thy-1+ BM stem cells shared more commonly expressed genes with hepatocytes. Overall, CBDL-derived beta2m-/Thy-1+ stem cells displayed a different transcriptomic fingerprint compared with beta2m-/Thy-1+ BM stem cells isolated from control rats; and CBDL-derived beta2m-/Thy-1+ stem cells started to express some hepatocyte-like genes.


Subject(s)
Bone Marrow Cells/cytology , Gene Expression Profiling , Liver/cytology , Stem Cells/cytology , Stem Cells/metabolism , Thy-1 Antigens/metabolism , Transcription, Genetic/genetics , Animals , Bone Marrow Cells/metabolism , Cells, Cultured , Common Bile Duct/metabolism , DNA Fingerprinting , Genomics , Liver/metabolism , Male , Organ Specificity , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Inbred Lew , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Up-Regulation , beta 2-Microglobulin/analysis
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