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1.
Domest Anim Endocrinol ; 75: 106603, 2021 04.
Article in English | MEDLINE | ID: mdl-33453567

ABSTRACT

Phosphoinositide 3-kinase (PI3K) is an enzyme that mediates endocrinological responses, such as intracellular signaling of insulin and growth factors, and plays important roles in muscle homeostasis and growth. In this study, the effect of antemortem PI3K activity on meat quality traits was investigated using broiler chickens whose PI3K was inhibited pharmacologically. Breast and thigh muscles were harvested from broilers treated with the PI3K inhibitor wortmannin, and meat quality traits were evaluated by determination of color, water-holding capacity, and breaking strength. The pH and concentrations of glycogen and free amino acids were also investigated as determinants of the chemical properties of meat. The results indicated that antemortem PI3K inhibition by wortmannin modified breast muscle color with lower L∗ values (P < 0.05) and b∗ values (P < 0.05) and higher a∗ values (P < 0.05). Antemortem PI3K inhibition also increased the water-holding capacity of breast muscles (P < 0.05), although breaking strength was not much affected. In addition, antemortem PI3K inhibition increased the concentrations of free amino acids in breast muscles, especially arginine (P < 0.05) and glutamic acid (P < 0.05). Similar effects were observed in thigh muscles. Lower glycogen levels at sacrifice (P < 0.05) and the resultant higher pH during the postmortem period (P < 0.05) were associated with PI3K inhibition-induced changes in meat quality traits. The wortmannin-treated muscles shared certain features with dark, firm, and dry meat which is a common abnormal meat. These findings suggest that antemortem PI3K activity contributes to meat quality traits and is involved in the molecular mechanism of the production of meat quality abnormalities.


Subject(s)
Chickens , Phosphatidylinositol 3-Kinases , Animals , Chickens/physiology , Meat/analysis , Muscle, Skeletal , Pectoralis Muscles/physiology , Phosphatidylinositol 3-Kinase
2.
Int J Sports Med ; 36(10): 814-21, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26038879

ABSTRACT

To examine palm cooling's (15 °C) impact, subjects performed 3 four-set leg press workouts in a randomized sequence. Per workout they received 1 of 3 treatments: no palm cooling, palm cooling between sets, or palm cooling between sets and post-exercise. Dependent variables were examined with three-way ANOVAs; average power underwent a three-way ANCOVA with body fat percentage as the covariate. Simple effects analysis was our post hoc and α=0.05. Left hand skin temperatures produced a two-way interaction (no palm cooling, palm cooling between sets>palm cooling between sets and post-exercise at several time points). A "high responder" subset had their data analyzed with an additional three-way ANOVA that again produced a two-way interaction (palm cooling between sets>no palm cooling>palm cooling between sets and post-exercise at multiple time points). Blood lactate results included a two-way interaction (no palm cooling>palm cooling between sets, palm cooling between sets and post-exercise at 0 min post-exercise). Average power yielded a two-way interaction (palm cooling between sets, palm cooling between sets>no palm cooling for the fourth set). Intermittent palm cooling hastened heat removal and blood lactate clearance, as well as delayed average power decrements.


Subject(s)
Cold Temperature , Hand/physiology , Resistance Training , Skin Temperature/physiology , Blood Pressure/physiology , Body Temperature Regulation , Female , Hand/blood supply , Heart Rate/physiology , Humans , Lactic Acid/blood , Male , Vasodilation/physiology
3.
Parasitology ; 142(4): 557-65, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25377129

ABSTRACT

Latent infection from Toxoplasma gondii (T. gondii) is widespread worldwide and has been associated with cognitive deficits in some but not all animal models and in humans. We tested the hypothesis that latent toxoplasmosis is associated with decreased cognitive function in a large cross-sectional dataset, the National Health and Nutrition Examination Survey (NHANES). There were 4178 participants aged 20-59 years, of whom 19.1% had IgG antibodies against T. gondii. Two ordinary least squares (OLS) regression models adjusted for the NHANES complex sampling design and weighted to represent the US population were estimated for simple reaction time, processing speed and short-term memory or attention. The first model included only main effects of latent toxoplasmosis and demographic control variables, and the second added interaction terms between latent toxoplasmosis and the poverty-to-income ratio (PIR), educational attainment and race-ethnicity. We also used multivariate models to assess all three cognitive outcomes in the same model. Although the models evaluating main effects only demonstrated no association between latent toxoplasmosis and the cognitive outcomes, significant interactions between latent toxoplasmosis and the PIR, between latent toxoplasmosis and educational attainment, and between latent toxoplasmosis and race-ethnicity indicated that latent toxoplasmosis may adversely affect cognitive function in certain groups.


Subject(s)
Cognition Disorders/complications , Toxoplasmosis/complications , Adult , Age Distribution , Cognition Disorders/epidemiology , Cross-Sectional Studies , Educational Status , Humans , Middle Aged , Models, Biological , Multivariate Analysis , Nutrition Surveys , Prevalence , Racial Groups , Regression Analysis , Sex Distribution , Toxoplasmosis/epidemiology , Young Adult
4.
Rural Remote Health ; 14(2): 2742, 2014.
Article in English | MEDLINE | ID: mdl-24930474

ABSTRACT

INTRODUCTION: Diabetes mellitus type II is a growing concern in the USA, with 6% of the population diagnosed with diabetes and another 5% having pre-diabetes. The prevalence of diabetes is 17% higher in rural areas than in central cities{1}. Adult diabetics living in rural areas often see negative outcomes related to their limited access to care, cultural barriers, and lack of educational resources. This article seeks to evaluate best evidence-based strategies directed at improving diabetic outcomes of rural populations through hemoglobin A1C (HbA1C) reductions. METHOD: A search of Medline, CIHNAL, PubMed, and Sage Pub was undertaken. The search was structured around the following key terms: adult, diabetes, education, hemoglobin a1c, and rural. The search limits were set to English-language publications between 2004 and 2012 in industrialized countries. Only articles from scholarly, peer-reviewed publications were considered. Literature that used an inpatient setting, focused on children or adolescents, and did not meet any inclusion criteria were excluded from this review. RESULTS: A total of 15 articles met the selection criteria from the 1819 citations sourced from the search. After reviewing the sources, nutritional patient education, motivational counseling and lifestyle modifications were found to be the most influential factors that favorably changed measurable outcomes for this population. Education for providers did not have an appreciable effect on patient outcomes. CONCLUSION: This review adds to the literature by outlining best-practice guidelines for evidence-based practice based on current research. Primary care providers in rural areas should encourage their patients to actively participate in diabetes education when possible, and provide this education in a culturally competent manner.


Subject(s)
Diabetes Mellitus, Type 2/prevention & control , Health Behavior , Patient Education as Topic/methods , Rural Population , Diet , Exercise , Glycated Hemoglobin , Humans , Life Style , United States
5.
Br J Surg ; 101(2): 17-22, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24375295

ABSTRACT

BACKGROUND: Small pigtail catheters appear to work as well as the traditional large-bore chest tubes in patients with traumatic pneumothorax, but it is not known whether the smaller pigtail catheters are associated with less tube-site pain. This study was conducted to compare tube-site pain following pigtail catheter or chest tube insertion in patients with uncomplicated traumatic pneumothorax. METHODS: This prospective randomized trial compared 14-Fr pigtail catheters and 28-Fr chest tubes in patients with traumatic pneumothorax presenting to a level I trauma centre from July 2010 to February 2012. Patients who required emergency tube placement, those who refused and those who could not respond to pain assessment were excluded. Primary outcomes were tube-site pain, as assessed by a numerical rating scale, and total pain medication use. Secondary outcomes included the success rate of pneumothorax resolution and insertion-related complications. RESULTS: Forty patients were enrolled. Baseline characteristics of 20 patients in the pigtail catheter group were similar to those of 20 patients in the chest tube group. No patient had a flail chest or haemothorax. Pain scores related to chest wall trauma were similar in the two groups. Patients with a pigtail catheter had significantly lower mean(s.d.) tube-site pain scores than those with a chest tube, at baseline after tube insertion (3.2(0.6) versus 7.7(0.6); P < 0.001), on day 1 (1.9(0.5) versus 6.2(0.7); P < 0.001) and day 2 (2.1(1.1) versus 5.5(1.0); P = 0.040). The decreased use of pain medication associated with pigtail catheter was not significantly different. The duration of tube insertion, success rate and insertion-related complications were all similar in the two groups. CONCLUSION: For patients with a simple, uncomplicated traumatic pneumothorax, use of a 14-Fr pigtail catheter is associated with reduced pain at the site of insertion, with no other clinically important differences noted compared with chest tubes. REGISTRATION NUMBER: NCT01537289 (http://clinicaltrials.gov).


Subject(s)
Catheterization/adverse effects , Chest Tubes/adverse effects , Pain/prevention & control , Pneumothorax/therapy , Thoracic Injuries/therapy , Analgesics/therapeutic use , Female , Humans , Male , Middle Aged , Pain/etiology , Pain Measurement , Prospective Studies , Treatment Outcome
7.
Am J Physiol Gastrointest Liver Physiol ; 302(1): G105-15, 2012 Jan 01.
Article in English | MEDLINE | ID: mdl-21921286

ABSTRACT

SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4(+) T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.


Subject(s)
Achlorhydria/immunology , Autoimmune Diseases/immunology , Gastritis/immunology , Ileitis/immunology , Achlorhydria/genetics , Achlorhydria/pathology , Adoptive Transfer , Animals , Autoantibodies/analysis , Autoantibodies/immunology , Autoimmune Diseases/genetics , Autoimmune Diseases/pathology , B-Lymphocytes/immunology , B-Lymphocytes/pathology , CD3 Complex/analysis , CD3 Complex/immunology , Female , Gastric Acid/metabolism , Gastritis/genetics , Gastritis/pathology , Ileitis/genetics , Ileitis/pathology , Leukocyte Common Antigens/analysis , Leukocyte Common Antigens/immunology , Male , Mice , Mice, Inbred C57BL , T-Lymphocytes/immunology , T-Lymphocytes/pathology , T-Lymphocytes, Helper-Inducer/immunology
8.
Poult Sci ; 90(7): 1562-73, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21673173

ABSTRACT

Studies were conducted in a Thai poultry plant to identify the factors that affected numbers of Campylobacter jejuni in chicken carcasses. The concentrations of Campylobacter were determined using the SimPlate most probable number and modified charcoal cefoperazone deoxycholate plating methods. Results indicated that the mean concentrations of C. jejuni in carcasses after scalding, plucking, and chilling were 2.93 ± 0.31, 2.98 ± 0.38, 2.88 ± 0.31, and 0.85 ± 0.95 log cfu, whereas the concentrations of C. jejuni in the scalding tank water, plucked feathers, and chicken breast portion were 1.39 ± 0.70, 3.28 ± 0.52, and 0.50 ± 1.22 log cfu, respectively. Sensitivity analysis using tornado order correlation analysis showed that risk parameters affecting the contamination of C. jejuni in the chicken slaughter and processing plant could be ranked as chilling water pH, number of pathogens in the scald tank water, scalding water temperature, number of C. jejuni on plucked feathers, and residual chlorine in the chill water, respectively. The exposure assessment and analysis of process parameters indicated that some of the current critical control points were not effective. The suggested interventions included preventing fecal contamination during transportation; increasing the scalding temperature, giving the scalding water a higher countercurrent flow rate; reducing contamination of feathers in the scalding tank to decrease C. jejuni in the scalding water; spraying water to reduce contamination at the plucking step; monitoring and maintaining the chill water pH at 6.0 to 6.5; and increasing the residual chlorine in the chill water. These interventions were recommended for inclusion in the hazard analysis and critical control point plan of the plant.


Subject(s)
Campylobacter Infections/veterinary , Campylobacter jejuni/isolation & purification , Food Handling/methods , Food Microbiology , Poultry Products/microbiology , Animals , Campylobacter Infections/microbiology , Campylobacter Infections/prevention & control , Chickens/microbiology , Colony Count, Microbial/veterinary , Computer Simulation , Food Handling/standards , Food Safety , Regression Analysis
9.
Plant Cell Rep ; 28(4): 703-17, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19214516

ABSTRACT

Eight Nicotiana benthamiana defensin genes were identified that could be divided into two classes with class II defensins being longer than class I defensins due to an additional acidic C-terminal domain. Class I defensins were NbDef1.1, NbDef1.2, NbDef1.3, NbDef1.4, NbDef1.5, and NbDef1.6, and class II were Nbdef2.1 and NbDef2.2. Relative RT-PCR showed that NbDef1.1, NbDef1.2, and NbDef1.4 had relatively similar expression levels in healthy leaves, stems, roots, flowers, and seeds. However, Nbdef1.3, NbDef1.5, and NbDef1.6 had varying degrees of tissue specific expression, and Nbdef2.1 and NbDef2.2 had strictly flower-specific expression. None of the defensins were significantly induced by infection by Colletotrichum destructivum or C. orbiculare. However, infection by Pseudomonas syringae pv. tabaci resulted in increased expression of Nbdef1.2 and Nbdef2.2, and decreased expression of NbDef1.1, NbDef1.4, and NbDef1.6. In the hypersensitive response of N. benthamiana containing Pto with P. syringae pv. tabaci containing AvrPto, only NbDef2.2 was significantly up-regulated. Expression of the genes was also affected by abiotic treatments. Both wounding and ethylene treatments resulted in a strong induction of NbDef2.2 and a moderate to weak induction of NbDef1.1, NbDef1.2, and NbDef1.4. Only weak or no induction was observed with treatment with benzothiadiazole. The expression of these eight defensin genes demonstrates that only a small fraction of the members of a defensin gene family will respond to a particular hemibiotrophic pathogen as well as to abiotic stress or signaling molecules.


Subject(s)
Defensins/metabolism , Ethylenes/pharmacology , Nicotiana/genetics , Plant Proteins/metabolism , Thiadiazoles/pharmacology , Colletotrichum/growth & development , Defensins/genetics , Gene Expression Regulation, Plant , Genes, Plant , Plant Diseases/genetics , Plant Proteins/genetics , Pseudomonas syringae/growth & development , RNA, Plant/metabolism , Sequence Analysis, DNA , Stress, Physiological , Time Factors , Nicotiana/metabolism
10.
G Ital Dermatol Venereol ; 144(1): 1-26, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19218908

ABSTRACT

Metastatic malignant melanoma is an incurable malignancy with extremely poor prognosis. Patients bearing this diagnosis face a median survival time of approximately 9 months with a probability of surviving 5 years after initial presentation at less than 5%. This is contrasted by the curative nature of surgical resection of early melanoma detected in the skin. To date, no systemic therapy has consistently and predictably impacted the overall survival of patients with metastatic melanoma. However, in recent years, a resurgence of innovative diagnostic and therapeutic developments have broadened our understanding of the natural history of melanoma and identified rational therapeutic targets/strategies that seem poised to significantly change the clinical outcomes in these patients. Herein we review the state-of-the-art in metastatic melanoma diagnostics and therapeutics with particular emphasis on multi-disciplinary clinical management.


Subject(s)
Melanoma/secondary , Melanoma/therapy , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Diagnosis, Differential , Evidence-Based Medicine , Fluorodeoxyglucose F18 , Humans , Immunotherapy , Magnetic Resonance Imaging , Melanoma/diagnosis , Melanoma/drug therapy , Melanoma/mortality , Melanoma/radiotherapy , Melanoma/surgery , Positron-Emission Tomography , Prognosis , Radiotherapy, Adjuvant , Skin Neoplasms/diagnosis , Skin Neoplasms/drug therapy , Skin Neoplasms/mortality , Skin Neoplasms/radiotherapy , Skin Neoplasms/surgery , Survival Analysis , Tomography, X-Ray Computed , Treatment Outcome
11.
Leukemia ; 23(3): 574-80, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18987657

ABSTRACT

Oncogenes involved in recurrent chromosomal translocations serve as diagnostic markers and therapeutic targets in hematopoietic tumors. In contrast to myeloid and B-cell neoplasms, translocations in peripheral T-cell lymphomas (PTCLs) are poorly understood. Here, we identified recurrent translocations involving the multiple myeloma oncogene-1/interferon regulatory factor-4 (IRF4) locus in PTCLs. IRF4 translocations exist in myeloma and some B-cell lymphomas, but have not been reported earlier in PTCLs. We studied 169 PTCLs using fluorescence in situ hybridization and identified 12 cases with IRF4 translocations. Two cases with t(6;14)(p25;q11.2) had translocations between IRF4 and the T-cell receptor-alpha (TCRA) locus. Both were cytotoxic PTCLs, unspecified (PTCL-Us) involving bone marrow and skin. In total, 8 of the remaining 10 cases were cutaneous anaplastic large-cell lymphomas (ALCLs) without TCRA rearrangements (57% of cutaneous ALCLs tested). These findings identified IRF4 translocations as a novel recurrent genetic abnormality in PTCLs. Cytotoxic PTCL-Us involving bone marrow and skin and containing IRF4/TCRA translocations might represent a distinct clinicopathologic entity. Translocations involving IRF4 but not TCRA appear to occur predominantly in cutaneous ALCLs. Detecting these translocations may be useful in lymphoma diagnosis. Further, due to its involvement in translocations, MUM1/IRF4 protein may play an important biologic role in some PTCLs, and might represent a possible therapeutic target.


Subject(s)
Interferon Regulatory Factors/genetics , Lymphoma, T-Cell, Cutaneous/genetics , Lymphoma, T-Cell, Peripheral/genetics , Oncogene Proteins, Fusion/genetics , Oncogenes , Skin Neoplasms/genetics , Translocation, Genetic , Adolescent , Adult , Aged , Aged, 80 and over , Bone Marrow Neoplasms/genetics , Child , Child, Preschool , Chromobox Protein Homolog 5 , Chromosomes, Human, Pair 14/genetics , Chromosomes, Human, Pair 14/ultrastructure , Chromosomes, Human, Pair 6/genetics , Chromosomes, Human, Pair 6/ultrastructure , Female , Humans , In Situ Hybridization, Fluorescence , Interferon Regulatory Factors/biosynthesis , Lymphoma, Primary Cutaneous Anaplastic Large Cell/genetics , Male , Middle Aged , Oncogene Proteins, Fusion/biosynthesis , Receptors, Antigen, T-Cell, alpha-beta/genetics , Young Adult
12.
Br J Dermatol ; 155(5): 988-93, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17034530

ABSTRACT

BACKGROUND: The risk of malignant melanoma associated with histologically dysplastic naevi (HDN) has not been defined. While clinically atypical naevi appear to confer an independent risk of melanoma, no study has evaluated the extent to which HDN are predictive of melanoma. OBJECTIVES: To estimate the risk of melanoma associated with HDN. Secondarily, the risk associated with number of naevi and large naevi is estimated. METHODS: We enrolled 80 patients with newly diagnosed melanoma along with 80 spousal controls. After obtaining information on melanoma risk factors and performing a complete cutaneous examination, the most clinically atypical naevus was biopsied in both cases and controls. Histological dysplasia was then assessed independently by 13 dermatopathologists (0, no dysplasia; 1, mild dysplasia; 2, moderate dysplasia; 3, severe dysplasia). The dermatopathologists were blinded as to whether the naevi were from melanoma subjects or controls. Multivariate analyses were performed to determine if there was an independent association between the degree of histological dysplasia in naevi and a personal history of melanoma. RESULTS: In persons with naevi receiving an average score of > 1 (i.e. naevi considered to have greater than mild histological dysplasia), there was an increased risk of melanoma [odds ratio (OR) 2.60, 95% confidence interval (CI) 0.99-6.86] which persisted after adjustment for confounders (OR 3.99, 95% CI 1.02-15.71). Very few dermatopathologists reliably graded naevi of subjects with melanoma as being more dysplastic than naevi of control subjects. Among the entire group, the interobserver reliability associated with grading histological dysplasia in naevi was poor (weighted kappa 0.28). CONCLUSIONS: HDN do appear to confer an independent risk of melanoma. However, this result may add more to our biological understanding of melanoma risk than to clinical assessment of risk, because HDN assessed by a single pathologist generally cannot be used to assess risk of melanoma. Future studies should be directed at establishing reproducible, predictive criteria for grading naevi.


Subject(s)
Dysplastic Nevus Syndrome/pathology , Melanoma/pathology , Skin Neoplasms/pathology , Adult , Case-Control Studies , Disease Progression , Female , Humans , Male , Melanoma/etiology , Middle Aged , Observer Variation , Pigmentation , Risk Factors , Severity of Illness Index , Skin Neoplasms/etiology
13.
Cancer Gene Ther ; 13(9): 886-95, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16645619

ABSTRACT

Administration of chemotherapy is often limited by myelosuppression. Expression of drug-resistance genes in hematopoietic cells has been proposed as a means to decrease the toxicity of cytotoxic agents. In this pilot study, we utilized a retroviral vector expressing methylguanine DNA methyltransferase (MGMT) to transduce hematopoietic progenitors, which were subsequently used in the setting of alkylator therapy (procarbazine, CCNU, vincristine (PCV)) for poor prognosis brain tumors. Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells were collected by apheresis and enriched for CD34+ expression. Nine subjects were infused with CD34+-enriched cells treated in a transduction procedure involving a 4-day exposure to cytokines with vector exposure on days 3 and 4. No major adverse event was related to the gene therapy procedure. Importantly, the engraftment kinetics of the treated product was similar to unmanipulated peripheral blood stem cells, suggesting that the ex vivo manipulation did not significantly reduce engrafting progenitor cell function. Gene-transduced cells were detected in all subjects. Although the level and duration was limited, patients receiving cells transduced using fibronectin 'preloaded' with virus supernatant appeared to show improved in vivo marking frequency. These findings demonstrate the feasibility and safety of utilizing MGMT-transduced CD34+ peripheral blood progenitor cells in the setting of chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/therapy , Genetic Therapy/methods , Genetic Vectors/genetics , Lomustine/therapeutic use , O(6)-Methylguanine-DNA Methyltransferase/genetics , Procarbazine/therapeutic use , Vincristine/therapeutic use , Adolescent , Adult , Antigens, CD34/metabolism , Antineoplastic Agents/therapeutic use , Brain Neoplasms/genetics , Colony-Forming Units Assay , DNA Primers , Female , Fibronectins/metabolism , Genetic Vectors/metabolism , Granulocyte Colony-Stimulating Factor/metabolism , Humans , Lomustine/administration & dosage , Male , Middle Aged , O(6)-Methylguanine-DNA Methyltransferase/metabolism , Peripheral Blood Stem Cell Transplantation/methods , Pilot Projects , Polymerase Chain Reaction , Procarbazine/administration & dosage , Retroviridae/genetics , Transduction, Genetic/methods , Vincristine/administration & dosage
14.
Transplant Proc ; 37(4): 1926-8, 2005 May.
Article in English | MEDLINE | ID: mdl-15919506

ABSTRACT

We measured the expression levels of transforming growth factor-beta (TGF-beta) and vascular cell adhesion molecule (VCAM-1) in rat kidney grafts undergoing chronic rejection and treated the rats with six different regimens in order to determine correlation between their expression levels and severity of chronic rejection. F344 or Lewis kidneys were transplanted into Lewis recipients to generate allograft or isograft groups, respectively. Graft recipients were treated with one of the following regimens: (1) untreated isograft, (2) untreated allograft, (3) tacrolimus (FK506), 1 mg/kg/d for 10 days, (4) triptolide (PG490-88), 0.5 mg/kg/d for 10 days, and (5) leflunomide analogue (FK778), 10 mg/kg/d for 10 days. Kidneys were harvested on day 90 after transplantation and subjected to histological analysis and gene expression analysis by real-time reverse transcriptase polymerase chain reaction (RT-PCR) for TGF-beta and VCAM-1. Gene expression values were compared to measurements of chronic rejection by linear regression analysis. Modified Banff score for transplant pathology show that chronic rejection was mild in the FK778 group, moderate in the PG490-88 group, and severe in the FK506 and allograft control groups. Overall, the expression levels of TGF-beta and VCAM-1 show high correlations with histological changes of chronic rejection. Suppression of the expression levels of TGF-beta and VCAM-1 is associated with the amelioration of chronic rejection by various drugs, suggesting that these molecules are important key molecules in chronic rejection.


Subject(s)
Gene Expression Regulation/physiology , Graft Rejection/prevention & control , Kidney Transplantation/immunology , Kidney Transplantation/pathology , Transforming Growth Factor beta/genetics , Vascular Cell Adhesion Molecule-1/genetics , Animals , Drug Therapy, Combination , Graft Rejection/drug therapy , Immunosuppressive Agents/therapeutic use , Male , Rats , Rats, Inbred F344 , Rats, Inbred Lew , Regression Analysis , Reverse Transcriptase Polymerase Chain Reaction
15.
Transplant Proc ; 37(4): 1962-4, 2005 May.
Article in English | MEDLINE | ID: mdl-15919518

ABSTRACT

Our previous study showed that PG490-88 effectively ameliorated both functional and histological changes of chronic rejection in the rat. In this experiment, we investigated the intragraft gene expression profiles of PG490-88 under successful prevention of chronic rejection in rat kidney allografts. Kidneys of F344 rats were transplanted into bilaterally nephrectomized LEW recipients. Recipients with a brief course of low-dose FK506 (1 mg/kg per day for 10 days) were dosed with PG490-88 0.5 mg/kg per day, which was predetermined and defined as the effective dose of preventing chronic allograft rejection in this model, for 90 days after grafting. Kidney grafts were harvested on day 90 after transplantation and subjected to gene expression analysis by real-time RT-PCR. Overall, the expression levels of all genes tested were upregulated in the brief course of low-dose FK506 control. PG490-88 treatment exhibited significant inhibition of intragraft m RNA levels of iNOS, IL-6, and perforin and marginal downregulation of IL-2, IFNgamma, IRF-1, TNFalpha, and TGFbeta. There was no change in IL-10, granzyme B, and PDGFalpha, when compared to the brief course of low-dose FK506 control. These results suggested that downregulation of multiple intragraft gene expression by mainly suppression of iNOS, IL-6, and perforin might be responsible for successful prevention of chronic kidney allograft nephropathy by PG490-88 in rats.


Subject(s)
Cytokines/genetics , Diterpenes/pharmacology , Gene Expression Profiling , Graft Rejection/prevention & control , Immunosuppressive Agents/pharmacology , Kidney Transplantation/physiology , Transplantation, Homologous/immunology , Animals , Kidney Transplantation/immunology , Rats , Rats, Inbred F344 , Reverse Transcriptase Polymerase Chain Reaction , Tacrolimus/pharmacology
16.
Transplant Proc ; 37(1): 134-6, 2005.
Article in English | MEDLINE | ID: mdl-15808572

ABSTRACT

PG490-88 is a semisynthetic derivative of the novel compound PG490 (triptolide) purified from a Chinese herb. It has been shown to prolong acute allograft survival in multiple experimental organ transplant models. However, the effect of PG490-88 on prevention of acute and chronic renal allograft rejection has not been determined. Kidneys of ACI or F344 rats were transplanted into bilaterally nephrectomized LEW recipients as the acute or chronic allograft rejection models, respectively. Treatment of LEW recipients with PG490-88 significantly prolonged ACI kidney graft survival in a dose-dependent manner when compared with the untreated allograft controls. LEW recipients of F344 kidney grafts who received PG490-88 for 90 days with a brief course of low-dose FK506 showed normal serum creatinine levels and markedly reduced histological changes of chronic rejection at day 90 after transplantation. These results suggest that PG490-88 significantly prolongs kidney allograft survival in an acute rejection model and prevents chronic allograft rejection in rats.


Subject(s)
Diterpenes/therapeutic use , Graft Rejection/prevention & control , Graft Survival/immunology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Acute Disease , Animals , Chronic Disease , Graft Rejection/pathology , Graft Survival/drug effects , Male , Rats , Rats, Inbred ACI , Rats, Inbred F344 , Rats, Inbred Lew , Time Factors , Transplantation, Homologous/immunology
17.
Vaccine ; 23(19): 2470-6, 2005 Mar 31.
Article in English | MEDLINE | ID: mdl-15752833

ABSTRACT

Recent years have seen an increase in the number of new vaccines available on the Canadian market, and increasing divergence in provincial and territorial immunization programs as jurisdictions must choose among available health interventions with limited funding. We present an analytical framework, which we have developed to assist in the analysis and comparison of potential immunization programs. The framework includes 58 criteria classified into 13 categories, including the burden of disease, vaccine characteristics and immunization strategy, cost-effectiveness, acceptability, feasibility, and evaluability of program, research questions, equity, ethical, legal and political considerations. To date this framework has been utilized in a variety of different contexts, such as to structure expert presentations and reports and to examine the degree of consensus and divergence among experts, and to establish priorities. It can be transformed for a variety of other uses such as educating health professionals and the general public about immunization.


Subject(s)
Health Services Research/methods , Immunization Programs , Canada , Health Policy , Humans
18.
Arch Androl ; 50(3): 181-5, 2004.
Article in English | MEDLINE | ID: mdl-15204685

ABSTRACT

Some men have elevated levels of sperm chromosome aneuploidy. In this study, we have evaluated and summarized sperm aneuploidy rates in male infertility patients and control groups. The mean aneuploidy rate for five chromosomes (X, Y, 13, 18, 21) was 1.2 +/- 0.1 for fertile controls, 1.4 +/- 0.1 for a general population control group, and 5.8 +/- 1.14 for the patients. When the patients were classified by the type of male factor infertility, the total aneuploidy rate was 2.6 +/- 0.3 in men with moderately diminished semen quality (n = 7), 4.0 +/- 0.3 patients with severe teratoasthenooligozoospermia, and 15.9 +/- 3.8 for men with rare ultrastructure defects such as round head only syndrome or severe tail agenesis. Some infertility patients have a severely elevated level of sperm chromosome aneuploidy, which may contribute to infertility or diminish the likelihood of a successful outcome from IVF/ICSI. The severity of sperm chromosome aneuploidy appears to be proportional to the severity of abnormal semen quality: in particular, abnormal morphology. The high rates of aneuploidy in patients with severe ultrastructure defects suggest that caution should be employed in counseling those patients prior to IVF/ICSI.


Subject(s)
Aneuploidy , Chromosomes, Human, Y/ultrastructure , Infertility, Male/genetics , Infertility, Male/pathology , Spermatozoa/pathology , Case-Control Studies , Humans , Male , Retrospective Studies , Severity of Illness Index , Spermatozoa/ultrastructure
19.
Meat Sci ; 67(1): 101-5, 2004 May.
Article in English | MEDLINE | ID: mdl-22061122

ABSTRACT

The degree of steak doneness is an important factor in providing consumers with a satisfying eating experience. Endpoint temperature and cooking rate are the determinants of degree of doneness. Our objectives were to predict internal temperature profiles and cooking times for longissimus lumborum and biceps femoris steaks. Each biceps femoris and longissimus lumborum steak was cooked individually in a gas-fired, forced-air-convection oven at 163 °C until the center temperature of each steak reached 70 °C. Temperature profiles were recorded by a Doric temperature recorder and the recorded time and temperature data were imported into a spreadsheet. A prediction method was then implemented to predict cooking times and temperature profiles. No significant differences (p<0.05) were found in cooking times between experimental and predicted values for either longissimus lumborum or biceps femoris steaks. Good agreement was found between experimental and predicted temperature profiles for the longissimus lumborum muscle. However, predicted temperature profiles were consistently higher (except for the beginning of the cooking cycle) than the experimental values up to 65 °C in the cooking cycle for biceps femoris steaks. A highly positive linear relationship was found between experimental and modeled temperature profiles for longissimus lumborum (R(2)=0.99), whereas a high quadratic (R(2)=0.99) relationship was found for biceps femoris steaks. Our method for predicting temperature profiles of steaks for a specified cooking time to attain a given degree of doneness should increase consumer satisfaction by reducing variation in meat sensory traits related to an expected degree of doneness.

20.
Arch Androl ; 49(1): 49-55, 2003.
Article in English | MEDLINE | ID: mdl-12647778

ABSTRACT

Previous studies have indicated that sperm quality may be related to unexplained recurrent pregnancy loss. This study evaluated the degree of sperm DNA fragmentation using the TUNEL assay on sperm from 24 couples with unexplained recurrent pregnancy loss (RPL) compared to sperm from 2 control groups: donors of known fertility and unscreened men from the general population. The percentage of sperm staining positive for DNA fragmentation was increased (p < .001) in the RPL group (38 +/- 4.2) compared to the donor (11.9 +/- 1.0) or general population (22 +/- 2.0) control groups. In the RPL group, no correlation was observed between semen quality parameters and the TUNEL data. These data indicate that some RPL patients have a significant increase of sperm DNA fragmentation, which may be causative of pregnancy loss in some patients.


Subject(s)
Abortion, Habitual/etiology , DNA Fragmentation , Spermatozoa/pathology , Female , Humans , In Situ Nick-End Labeling , Male , Pregnancy
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