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1.
Balkan J Med Genet ; 25(2): 51-62, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37265972

RESUMO

Background: Thalassemia, as the most common single-gene genetic disorder, is related to a defect in the synthesis of one or more hemoglobin chains. More than 200 mutations have been identified in the ß-globin gene. Globally, every susceptible racial group has its own specific spectrum of the common mutations that are well-known to a particular geographic region. On the other hand, varying numbers of diverse rare mutations may occur. Materials and Methods: The subjects of the study included 2113 heterozygote or homozygote ß-thalassemia cases selected among couples who participated in the Iranian national thalassemia screening program from January 2011 to November 2019. Molecular characterization of the ß-thalassemia mutation was initially carried out by the amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) technique for common mutations, followed by sequencing, Gap PCR, and Multiple ligation-dependent probe amplification (MLPA) methods - in cases not detected by the ARMS-PCR. Results: The existence of 39 rare and new point mutations and 4 large deletions were described in our cohort. Sicilian (-13,337bp) deletion, CD36/37 (-T), and CD15 TGG>TGA were encountered more often than the others in a decreasing order, in terms of frequency. The least frequent mutations/deletions were deletion from HBD exon 1 to HBB promoter, 619 bp deletion, Deletion from up HBBP1-Exon3 HBBP1 and up HBB-0.5Kb down HBB, CAP+8 C>A, CD37 (G>A), CD6 (-A), IVSI-2 (T>C), IVSII-705 T>G, and IVSII-772 (G>A). Each occurred once. Five mutations/variants were also determined which have not been reported previously in Iran. Conclusion: According to the findings of the study, the Northwestern Iranian population displayed a wide variety of thalassemia allelic distributions. Identification of rare and new mutations in the ß-thalassemia in the national population is beneficial for screening programs, genetic counseling, and prenatal diagnosis.

2.
Nature ; 474(7352): 487-9, 2011 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-21654747

RESUMO

Supernovae are stellar explosions driven by gravitational or thermonuclear energy that is observed as electromagnetic radiation emitted over weeks or more. In all known supernovae, this radiation comes from internal energy deposited in the outflowing ejecta by one or more of the following processes: radioactive decay of freshly synthesized elements (typically (56)Ni), the explosion shock in the envelope of a supergiant star, and interaction between the debris and slowly moving, hydrogen-rich circumstellar material. Here we report observations of a class of luminous supernovae whose properties cannot be explained by any of these processes. The class includes four new supernovae that we have discovered and two previously unexplained events (SN 2005ap and SCP 06F6) that we can now identify as members of the same class. These supernovae are all about ten times brighter than most type Ia supernova, do not show any trace of hydrogen, emit significant ultraviolet flux for extended periods of time and have late-time decay rates that are inconsistent with radioactivity. Our data require that the observed radiation be emitted by hydrogen-free material distributed over a large radius (∼10(15) centimetres) and expanding at high speeds (>10(4) kilometres per second). These long-lived, ultraviolet-luminous events can be observed out to redshifts z > 4.

3.
Ann Oncol ; 27(7): 1241-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27029708

RESUMO

BACKGROUND: AE37 is the Ii-Key hybrid of the MHC class II peptide, AE36 (HER2 aa:776-790). Phase I studies showed AE37 administered with granulocyte macrophage colony-stimulating factor (GM-CSF) to be safe and highly immunogenic. A prospective, randomized, multicenter phase II adjuvant trial was conducted to evaluate the vaccine's efficacy. METHODS: Clinically disease-free node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 [immunohistochemistry (IHC) 1-3+] were enrolled. Patients were randomized to AE37 + GM-CSF versus GM-CSF alone. Toxicity was monitored. Clinical recurrences were documented and disease-free survival (DFS) analyzed. RESULTS: The trial enrolled 298 patients; 153 received AE37 + GM-CSF and 145 received GM-CSF alone. The groups were well matched for clinicopathologic characteristics. Toxicities have been minimal. At the time of the primary analysis, the recurrence rate in the vaccinated group was 12.4% versus 13.8% in the control group [relative risk reduction 12%, HR 0.885, 95% confidence interval (CI) 0.472-1.659, P = 0.70]. The Kaplan-Meier estimated 5-year DFS rate was 80.8% in vaccinated versus 79.5% in control patients. In planned subset analyses of patients with IHC 1+/2+ HER2-expressing tumors, 5-year DFS was 77.2% in vaccinated patients (n = 76) versus 65.7% in control patients (n = 78) (P = 0.21). In patients with triple-negative breast cancer (HER2 IHC 1+/2+ and hormone receptor negative) DFS was 77.7% in vaccinated patients (n = 25) versus 49.0% in control patients (n = 25) (P = 0.12). CONCLUSION: The overall intention-to-treat analysis demonstrates no benefit to vaccination. However, the results confirm that the vaccine is safe and suggest that vaccination may have clinical benefit in patients with low HER2-expressing tumors, specifically TNBC. Further evaluation in a randomized trial enrolling TNBC patients is warranted.


Assuntos
Vacinas Anticâncer/administração & dosagem , Receptor ErbB-2/imunologia , Neoplasias de Mama Triplo Negativas/prevenção & controle , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Vacinas Anticâncer/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/uso terapêutico , Receptor ErbB-2/genética , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia
4.
Clin Exp Dermatol ; 41(6): 591-4, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27061305

RESUMO

BACKGROUND: Sequential audits over a recent 30-year period from 1981 to 2010 have documented dermatological activity data for the same region of southeast Scotland approximately every 5 years, allowing demonstration of trends in workload. AIM: To undertake similar assessments of outpatient dermatological activity using historical documentation from 1921 to 1965, and to compare trends with modern data. METHODS: Historical records held in the libraries of the Department of Dermatology, Royal Infirmary, Edinburgh and in the University of Edinburgh were audited. Details of new dermatological outpatients were recorded for the months of September, October and November from 1921, and at 5-year intervals from 1925 to 1965. Patient age, sex and primary diagnosis were documented. Data were analysed and compared with those of previous audits of the same geographical population from 1981 to 2010. RESULTS: Details of 11 225 new patients were analysed during the period 1921-1965, in conjunction with 7755 patients from the period 1981-2010, giving a total of 18 980 patients included in the study. The monthly number of patients increased by over 3000%, from 74 patients in 1921-2882 patients in 2010. Trends were seen in the following diagnostic categories. Between 1921 and 2010, benign tumours increased from 1% to 36% of workload and malignant tumours from 2% to 11%. Over the same time period, dermatitis decreased from 32% to 13%, and infections from 24% to 2%. Infestations referrals peaked at 12% in the 1940s, but declined to 1% in the 1950s. Viral warts peaked at 49% of patients in 1960 and fell to 3% in 2010. CONCLUSIONS: Over a 90-year period, there has been a dramatic rise in new patient dermatological workload. We have found trends in presentations of common dermatological conditions. Outpatient dermatology now appears to be increasingly involved in the detection and treatment of skin malignancy. Although many inflammatory dermatoses remain important, infectious dermatoses are less commonly encountered, compared with historical activity.


Assuntos
Auditoria Clínica/métodos , Dermatologia/história , Dermatopatias/epidemiologia , Neoplasias Cutâneas/epidemiologia , Carga de Trabalho/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Dermatite , Dermatologia/estatística & dados numéricos , História do Século XX , História do Século XXI , Humanos , Infecções , Pessoa de Meia-Idade , Encaminhamento e Consulta , Escócia/epidemiologia , Dermatopatias/microbiologia , Dermatopatias/patologia , Verrugas/virologia
5.
Mol Hum Reprod ; 19(10): 687-96, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23689979

RESUMO

Preterm birth (PTB) is a complex trait, but little is known regarding its major genetic determinants. The objective of this study is to localize genes that influence susceptibility to PTB in Mexican Americans (MAs), a minority population in the USA, using predominantly microfilmed birth certificate-based data obtained from the San Antonio Family Birth Weight Study. Only 1302 singleton births from 288 families with information on PTB and significant covariates were considered for genetic analysis. PTB is defined as a childbirth that occurs at <37 completed weeks of gestation, and the prevalence of PTB in this sample was 6.4%. An ∼10 cM genetic map was used to conduct a genome-wide linkage analysis using the program SOLAR. The heritability of PTB was high (h(2) ± SE: 0.75 ± 0.20) and significant (P = 4.5 × 10(-5)), after adjusting for the significant effects of birthweight and birth order. We found significant evidence for linkage of PTB (LOD = 3.6; nominal P = 2.3 × 10(-5); empirical P = 1.0 × 10(-5)) on chromosome 18q between markers D18S1364 and D18S541. Several other chromosomal regions (2q, 9p, 16q and 20q) were also potentially linked with PTB. A strong positional candidate gene in the 18q linked region is SERPINB2 or PAI-2, a member of the plasminogen activator system that is associated with various reproductive processes. In conclusion, to our knowledge, perhaps for the first time in MAs or US populations, we have localized a major susceptibility locus for PTB on chromosome 18q21.33-q23.


Assuntos
Predisposição Genética para Doença/genética , Nascimento Prematuro/genética , Cromossomos Humanos Par 18/genética , Feminino , Ligação Genética/genética , Humanos , Americanos Mexicanos/genética , Gravidez
6.
J Public Health (Oxf) ; 34 Suppl 1: i11-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22363026

RESUMO

Adolescence has long been considered a period of increased risk behaviour. This supposition has been supported by a wealth of empirical evidence and recently, health risk behaviours have been identified as a key mechanism for the general deterioration of adolescent health relative to other age groups. Research regarding adolescent risk behaviour suggests that there are often strong links between individual risk behaviours. The mechanisms for these associations have been attributed to common risk and protective factors, as well as gateway effects stemming from increased accessibility to additional risk behaviours. This has important implications for policy interventions designed to reduce risk behaviours in adolescence. Not only does a multiple risk behaviour approach increase the effectiveness of individual risk behaviour policy, but it is also conducive to a more cohesive, coherent and efficient approach to adolescent risk in general. Several examples of cohesive policy responses to multiple risk behaviours have emerged, but generally, policy remains segregated into individual risk domains. With increasing evidence for the effectiveness of integrated approaches, multiple risk behaviours require consideration to design and implement effective and efficient policy responses.


Assuntos
Comportamento do Adolescente/psicologia , Comportamentos Relacionados com a Saúde , Política de Saúde , Promoção da Saúde/normas , Assunção de Riscos , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Sexo sem Proteção/prevenção & controle , Adolescente , Causas de Morte/tendências , Criança , Comorbidade , Países Desenvolvidos/estatística & dados numéricos , Promoção da Saúde/métodos , Humanos , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Reino Unido/epidemiologia , Estados Unidos/epidemiologia , Sexo sem Proteção/efeitos dos fármacos , Sexo sem Proteção/estatística & dados numéricos , Adulto Jovem
7.
Am J Transplant ; 9(1): 124-31, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18976300

RESUMO

Pretransplant exposure to donor antigen is known to modulate recipient alloimmunity, and frequently results in sensitization. However, donor-specific transfusion (DST) can have a protolerant effect that is dependent on route, dose and coadministered immunosuppression. Rodent studies have shown in some strain combinations that portal venous (PV) DST alone can induce tolerance, and uncontrolled clinical use of PVDST has been reported. In order to determine if pretransplant PVDST has a clinically relevant salutary effect, we studied it and the influence of concomitant immunosuppression in rhesus monkeys undergoing renal allotransplantation. Animals received PVDST with unfractionated bone marrow and/or tacrolimus or sirolimus 1 week prior to transplantation. Graft survival was assessed without any posttransplant immunosuppression. PVDST alone or in combination with tacrolimus was ineffective. However, PVDST in combination with sirolimus significantly prolonged renal allograft survival to a mean of 24 days. Preoperative sirolimus alone had no effect, and peripheral DST with sirolimus prolonged graft survival in 2/4 animals, but resulted in accelerated rejection in 2/4 animals. These data demonstrate that PVDST in combination with sirolimus delays rejection in a modest but measurable way in a rigorous model. It may thus be a preferable method for donor antigen administration.


Assuntos
Sobrevivência de Enxerto , Imunossupressores/uso terapêutico , Isoantígenos/administração & dosagem , Transplante de Rim , Sirolimo/uso terapêutico , Animais , Quimera , Rejeição de Enxerto/prevenção & controle , Tolerância Imunológica , Macaca mulatta
9.
Meat Sci ; 81(2): 335-43, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22064172

RESUMO

A market basket survey for beef retail cut composition at the retail level (four stores each from two chains in each city) was conducted in 11 US cities from January to March 2006. Beef cuts (n=17,495) were measured for external fat thickness with cuts from the chuck (0.05cm), round (0.05cm), and miscellaneous (0.04cm) having less (P<0.05) fat than cuts from the loin (0.11cm) and rib (0.11cm). Beef cuts (n=1327) were separated physically into separable components with round cuts having more (P<0.05) separable lean (96.63%) than chuck cuts (86.81%) and miscellaneous cuts (86.18%), which had more (P<0.05) separable lean than loin cuts (84.53%) with rib cuts (69.34%) having the lowest (P<0.05) separable lean. Chemical fat from the separable lean differed (P<0.05) between each cut category: round cuts (3.71%), miscellaneous cuts (4.99%), loin cuts (5.60%), chuck cuts (6.90%), and rib cuts (8.61%). Ground beef samples (n=235), with declared lean/fat percentages ranging from 73/27 to 96/4, had overall chemical fat values of 13.41% and moisture values of 67.42%. This survey documents the current beef retail cut and ground beef composition, which is helpful to those who need this information for various dietary and marketing purposes.

10.
Am J Transplant ; 8(6): 1297-302, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18444933

RESUMO

Valganciclovir is commonly used for cytomegalovirus (CMV) prophylaxis in renal transplant patients. A fixed dose of 900 mg daily is typically recommended, however, there has never been a formal pharmacokinetic study comparing various doses in renal transplant patients. We therefore compared the pharmacokinetic characteristics of intravenous ganciclovir (IV GCV) and oral ganciclovir (GCV) with two different doses of valganciclovir (VGCV) in an open-label crossover study. Ten adult kidney recipients participated in a four-phase crossover treatment schedule of IV GCV (2.5 mg/kg every 12 h), VGCV (900 mg daily), VGCV (450 mg daily) and oral GCV (1000 mg Q8 H). IV GCV and oral VGCV 900 mg daily achieved similar values for AUC(0-24) (median 60.63 vs. 62.86 microg/h/mL). Oral VGCV 450 mg achieved comparable AUC(0-24) values as oral GCV 1000 mg Q8 H (median AUC(0-24) 35.9 vs. 29.04 microg/h/mL). Oral VGCV 900 mg daily provided systemic GCV exposure similar to IV GCV and confirms PV 16 000 study results. Further, VGCV 450 mg daily provided comparable systemic exposure versus oral GCV. Due to its favorable pharmacokinetic profile, data herein suggest that VGCV can be used in the early post-kidney transplant period, and that 450 mg daily provides ample drug exposure for effective CMV prophylaxis in kidney transplant patients.


Assuntos
Antivirais/farmacocinética , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/análogos & derivados , Transplante de Rim , Adulto , Antivirais/administração & dosagem , Estudos Cross-Over , Infecções por Citomegalovirus/etiologia , Relação Dose-Resposta a Droga , Feminino , Ganciclovir/administração & dosagem , Ganciclovir/farmacocinética , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valganciclovir
11.
J Food Prot ; 71(2): 405-10, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18326196

RESUMO

Effects of 10% xylitol (a five-carbon sugar alcohol) on adhesion of Escherichia coli O157:H7 and Salmonella Typhimurium to meat surfaces were examined with three approaches. First, beef outside round was inoculated with rifampin-resistant E. coli O157:H7 and Salmonella Typhimurium dispersed in xylitol or peptone solution. Samples were rinsed with water or not rinsed in a 2 x 2 factorial arrangement. No interaction existed between inoculum and rinsing treatments (P > 0.84). Incubation in xylitol had minimal impact on pathogen adhesion (P > 0.76); however, rinsing reduced pathogen cell counts (P < 0.01). Second, meat samples were treated with water, xylitol, or no rinse; inoculated with pathogens dispersed in peptone solution (8.6 log CFU/ml for each pathogen); and then treated with water, xylitol, or no rinse in a 3 x 3 factorial arrangement. No interactions were observed (P > 0.50). Postinoculation rinsing reduced pathogen loads (P < 0.01) without difference between water and xylitol (P > 0.64). Third, carcass surfaces inoculated with pathogens (5.5 log CFU/cm2) were treated with 35 degrees C water wash, 2.5% L-lactic acid spray, 10% xylitol spray, lactic acid plus xylitol, or hot water plus xylitol. Lactic acid treatments reduced Salmonella Typhimurium at 0 h (P < 0.01) and 24 h (P < 0.02). Hot water treatments tended to reduce Salmonella Typhimurium at 0 h (P < 0.07). Xylitol did not reduce pathogens (P > 0.62) or increase effectiveness of other treatments. Xylitol does not influence E. coli O157:H7 and Salmonella Typhimurium adhesion to meat surfaces.


Assuntos
Aderência Bacteriana/fisiologia , Bovinos/microbiologia , Escherichia coli O157/fisiologia , Contaminação de Alimentos/análise , Salmonella typhimurium/fisiologia , Xilitol/farmacologia , Animais , Contagem de Colônia Microbiana , Relação Dose-Resposta a Droga , Escherichia coli O157/efeitos dos fármacos , Manipulação de Alimentos/métodos , Microbiologia de Alimentos , Humanos , Salmonella typhimurium/efeitos dos fármacos , Saneamento , Edulcorantes/farmacologia
12.
J Clin Invest ; 81(1): 171-5, 1988 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3335634

RESUMO

Genetic deficiency of short-chain acyl-coenzyme A (CoA) dehydrogenase activity was demonstrated in cultured fibroblasts from a 2-yr-old female whose early postnatal life was complicated by poor feeding, emesis, and failure to thrive. She demonstrated progressive skeletal muscle weakness and developmental delay. Her plasma total carnitine level (35 nmol/ml) was low-normal, but was esterified to an abnormal degree (55% vs. control of less than 10%). Her skeletal muscle total carnitine level was low (7.6 nmol/mg protein vs. control of 14 +/- 2 nmol/mg protein) and was 75% esterified. Mild lipid deposition was noted in type I muscle fibers. Fibroblasts from this patient had 50% of control levels of acyl-CoA dehydrogenase activity towards butyryl-CoA as substrate at a concentration of 50 muM in a fluorometric assay based on the reduction of electron transfer flavoprotein. All of this residual activity was inhibited by an antibody against medium-chain acyl-CoA dehydrogenase. These data demonstrated that medium-chain acyl-CoA dehydrogenase accounted for 50% of the activity towards the short-chain substrate, butyryl-CoA, under these conditions, but that antibody against that enzyme could be used to unmask the specific and virtually complete deficiency of short-chain acyl-CoA dehydrogenase in this patient. Fibroblasts from her parents had intermediate levels of activity towards butyryl-CoA, consistent with the autosomal recessive inheritance of this metabolic defect.


Assuntos
Acil-CoA Desidrogenases/deficiência , Fibroblastos/enzimologia , Músculos/enzimologia , Acil-CoA Desidrogenase , Acil-CoA Desidrogenases/antagonistas & inibidores , Acil-CoA Desidrogenases/genética , Acil-CoA Desidrogenases/imunologia , Adolescente , Adulto , Anticorpos/fisiologia , Carnitina/deficiência , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Músculos/fisiopatologia , Especificidade por Substrato
13.
J Clin Invest ; 87(3): 778-86, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1847937

RESUMO

Elevated concentrations of cytokines were found in the plasma of patients acutely ill with Reye syndrome (RS) but not in control subjects or recovered RS patients. To determine whether this disorder involves a genetically determined abnormal response to cytokines, the effects of tumor necrosis factor (TNF) and IL-1 on intracellular free Ca2+ were compared in cultured skin fibroblasts from control subjects and patients with RS. IL-1 and TNF caused rapid, transient, and concentration-dependent increases in cytosolic free Ca2+. The peak cytosolic free Ca2+ was greater and occurred at higher concentrations of IL-1 and TNF in patient cells than in cells from age-matched controls. In control cells, the Ca2+ transient diminished sharply with increasing amounts of IL-1 or TNF above the maximum stimulatory concentration. In contrast, in patient fibroblast this bell-shaped curve of concentration dependency was much less apparent. Bradykinin-stimulated Ca2+ transients were similar in the two groups and did not exhibit the bell-shaped concentration dependency. Thus, plasma cytokine levels are elevated in RS patients and the Ca2+ response to cytokines is increased in cells derived from these patients. We propose that the increased response reflects a genetic defect in cytokine receptor-modulated signal transduction.


Assuntos
Cálcio/fisiologia , Interleucina-1/farmacologia , Síndrome de Reye/fisiopatologia , Fator de Necrose Tumoral alfa/farmacologia , Adolescente , Bradicinina/farmacologia , Bucladesina/farmacologia , Células Cultivadas , Criança , Humanos , Técnicas In Vitro , Interleucina-6/sangue , Receptores de Superfície Celular/fisiologia , Receptores Imunológicos/fisiologia , Receptores de Interleucina-1 , Receptores do Fator de Necrose Tumoral , Transdução de Sinais , Fenômenos Fisiológicos da Pele , Acetato de Tetradecanoilforbol/farmacologia
14.
J Clin Invest ; 82(3): 782-8, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3417871

RESUMO

This study examines the relationship between impaired fatty acid oxidation and the pathogenesis of Reye syndrome. We present a hypothesis proposing that many clinical signs of this childhood disease are caused by accumulation of unusual acyl CoA esters, precursors to deacylated metabolites found in the patients' blood and urine. A new method was developed to measure acyl CoA compounds in small human liver biopsy samples, offering several advantages over previous techniques. A major finding was an accumulation in Reye syndrome patients of short- and medium-chain acyl CoA intermediates of fatty acid and branched-chain amino acid oxidation. These metabolites included octanoyl, isovaleryl, butyryl, isobutyryl, propionyl, and methylmalonyl CoA esters. The findings were explained in a model of hepatic fatty acid oxidation involving three interrelated pathways: mitochondrial beta-oxidation, peroxisomal beta-oxidation, and omega-oxidation in the endoplasmic reticulum. The results suggest that pathogenesis in Reye syndrome stems from generalized mitochondrial damage resulting in accumulation of acyl CoA esters. High levels of these compounds lead to inhibition of mitochondrial pathways for ureogenesis, gluconeogenesis, and fatty acid oxidation. The inhibited pathways, in turn, could cause the hyperammonemia, hypoglycemia, and hypoketonemia observed in patients. The model also explains underlying biochemical differences between patients with Reye syndrome and medium-chain acyl CoA dehydrogenase deficiency, another disorder of fatty acid metabolism. Acetyl CoA levels, in the latter disease, were dramatically decreased, compared with both human controls and Reye syndrome patients.


Assuntos
Acil Coenzima A/metabolismo , Fígado/enzimologia , Síndrome de Reye/etiologia , Acil Coenzima A/análise , Nucleotídeos de Adenina/análise , Adolescente , Criança , Feminino , Humanos , Masculino , Malonil Coenzima A/análise , Nucleotídeos de Pirimidina/análise , Síndrome de Reye/enzimologia
15.
Meat Sci ; 75(1): 150-8, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22063423

RESUMO

Bos indicus crossbred cattle (n=79) were fed vitamin D(3) (0 or 3 million IU/hd/d) for 5d. Afterwards, half of each group was slaughtered immediately, while half was fed, without supplementation, for 7d before processing. Serum calcium concentration was increased (P<0.05) in cattle after supplement removal, but not immediately following supplementation. This also was observed in the M. longissimus lumborum and M. triceps brachii, but not in the M. semitendinosus. Liver biopsy vitamin D(3) concentrations were higher (P<0.05) in supplemented cattle immediately following supplementation, but were not different from controls after supplement removal. Vitamin D(3) did not affect tenderness at supplement removal day 0, but increased the tenderness of the M. longissimus lumborum and M. semitendinosus at supplement removal day 7. Vitamin D(3) supplementation improves muscle tenderness and may be more effective when supplementation is ceased 7d before slaughter, with minimum food safety concerns.

16.
Meat Sci ; 77(3): 357-64, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22061788

RESUMO

Beef from retail and foodservice establishments in 11 US cities was evaluated using Warner-Bratzler shear (WBS) and consumer evaluation panels. Postmortem aging times ranged from 3 to 83d for retail and 7 to 136d for foodservice with mean aging times of 22.6d and 30.1d, respectively. For retail, the three cuts from the round - top round, bottom round, and eye of round - had the highest (P<0.05) WBS values compared to cuts from the chuck, rib, and loin. Top loin steaks had the lowest (P<0.05) WBS value compared to ribeye and top sirloin foodservice steaks. Retail bone-in top loin, top loin, ribeye, T-bone, and porterhouse received the highest (P<0.05) ratings by consumers for overall like and like tenderness. Quality grade had little or no effect on foodservice sensory evaluations. Improvements in round tenderness are needed to increase consumer acceptability.

17.
J Cancer ; 8(7): 1255-1262, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28607601

RESUMO

INTRODUCTION: Peptide vaccines offer anti-tumor efficacy with very low toxicity. However, repeat stimulation with an immunogenic peptide leads to activation induced cell death (AICD), decreasing efficacy. We engineered variants of an immunogenic peptide (E39) and tested their ability to induce a robust, sustainable immune response. METHODS: Multiple variants of E39 were created by exchanging 1 or 2 amino acids. We tested the PBMC proliferation, cytokine production and cytolytic activity induced by each variant peptide. RESULTS: Repeated stimulation with E39 likely led to in vitro AICD, while stimulation with E39' led to T-cell proliferation with less evidence of AICD, modest cytokine production and high CTL activity. CONCLUSIONS: E39' appears to be the optimal variant of E39 for inducing effective long-term immunity.

18.
Transl Anim Sci ; 1(3): 320-332, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32704657

RESUMO

The National Beef Quality Audit (NBQA) is conducted every 5 yr and was most recently again conducted in 2016. Face-to-face interviews gauged progress in quality associated with live cattle production using procedures first utilized in NBQA 2011. The 2016 NBQA was the first in which interviews concerning fed steers and heifers were combined with an audit of market cow and bull beef. Face-to-face interviews were designed to illicit definitions for beef quality, estimate willingness to pay (WTP) for quality attributes, establish relative importance rankings for important quality factors, and assess images, strengths, weaknesses, potential threats, and shifting trends in the beef industry since the 2011 audit. Individuals making purchasing decisions in 5 market sectors of the steer/heifer and cow/bull beef supply chain were interviewed, including packers (n = 36), retailers (including large and small supermarket companies and warehouse food sales companies; n = 35), food service operators (including quick-serve, full-service, and institutional establishments; n = 29), further processors (n = 64), and peripherally-related government and trade organizations (GTO; n = 30). Face-to-face interviews were conducted between January and November of 2016 using a designed dynamic routing system. Definitions (as described by interviewees) for 7 pre-determined quality factors, including: (1) How and where the cattle were raised, (2) Lean, fat, and bone, (3) Weight and size, (4) Visual characteristics, (5) Food safety, (6) Eating satisfaction, and (7) Cattle genetics were recorded verbatim and categorized into similar responses for analysis. Compared to NBQA-2011, a higher percentage of companies were willing to pay premiums for guaranteed quality attributes, but overall were willing to pay lower average premiums than the companies interviewed in 2011. Food safety had the highest share of preference among all interviewees, generating a double-digit advantage over any other quality factor. The 2 beef industries have an overall positive image among interviewees, and despite lingering weaknesses, product quality continued to be at the forefront of the strengths category for both steer and heifer beef and market cow and bull beef.

19.
Transl Anim Sci ; 1(2): 229-238, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32704647

RESUMO

The National Beef Quality Audit-2016 (NBQA-2016) was conducted to assess current transportation, mobility, and quality characteristics of U.S. fed steers and heifers. Data were collected at 17 beef processing facilities between March and November 2016. About 8,000 live cattle were evaluated for transportation and mobility, and about 25,000 carcasses were evaluated on the slaughter floor. Cattle were in transit to the slaughter facility for a mean duration of 2.7 h from a mean distance of 218.5 km using trailers with dimensions ranging from 17.84 m2 to 59.09 m2. Area allotted per animal averaged 1.13 m2 and ranged from 0.85 m2 to 2.28 m2. A total of 96.8% of cattle received a mobility score of 1 (walks easily, no apparent lameness). Identification types (35.1% had multiple) were lot visual tags (61.5%), individual tags (55.0%), electronic tags (16.9%), metal-clip tags (9.2%), bar-coded tags (0.05%), wattles (0.01%), and other (2.6%). Cattle were black-hided (57.8%), Holstein (20.4%), red-hided (10.5%), yellow-hided (4.8%), gray-hided (2.9%), brown-hided (1.3%), and white-hided (1.1%). Unbranded hides were observed on 74.3% of cattle; 18.6% had brands located on the butt, 6.3% on the side, and 1.3% on the shoulder (values exceed 100% due to multiple brands). For hide-on carcasses, 37.7% displayed no mud or manure; specific locations for mud or manure were legs (40.8%), belly (33.0%), tail region (15.5%), side (6.8%), and top-line (3.9%). Cattle without horns represented 83.3% of the sample, and cattle that did have horns measured: < 2.54 cm (5.5%), 2.54 to 12.7 cm (8.3%), and > 12.7 cm (2.9%). Carcasses without bruises represented 61.1% of those sampled, whereas 28.2% had 1, 8.2% had 2, 2.1% had 3, and 0.3% had 4 bruises. Of those carcasses with a bruise, the bruise was located on the loin (29.7%), round (27.8%), chuck (16.4%), rib (14.4%), and brisket/plate/flank (11.6%). Frequencies of offal condemnations were livers (30.8%), lungs (18.2%), viscera (16.3%), hearts (11.1%), heads (2.7%), and tongues (2.0%). Compared to NBQA-2011, fewer cattle were identified for traceability, fewer were black-hided, a greater number were Holstein cattle, more with no brand and no horns, fewer without bruises, more liver, lung, and viscera condemnations, and fewer heads and tongues were condemned. The NBQA remains an influential survey for the U.S. beef industry to provide benchmarks and strategic plans for continued improvement of beef quality and consistency.

20.
Transl Anim Sci ; 1(4): 570-584, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32704679

RESUMO

The National Beef Quality Audit-2016 marks the fourth iteration in a series assessing the quality of live beef and dairy cows and bulls and their carcass counterparts. The objective was to determine the incidence of producer-related defects, and report cattle and carcass traits associated with producer management. Conducted from March through December of 2016, trailers (n = 154), live animals (n = 5,470), hide-on carcasses (n = 5,278), and hide-off hot carcasses (n = 5,510) were surveyed in 18 commercial packing facilities throughout the United States. Cattle were allowed 2.3 m2 of trailer space on average during transit indicating some haulers are adhering to industry handling guidelines for trailer space requirements. Of the mixed gender loads arriving at processing facilities, cows and bulls were not segregated on 64.4% of the trailers surveyed. When assessed for mobility, the greatest majority of cattle surveyed were sound. Since the inception of the quality audit series, beef cows have shown substantial improvements in muscle. Today over 90.0% of dairy cows are too light muscled. The mean body condition score for beef animals was 4.7 and for dairy cows and bulls was 2.6 and 3.3, respectively. Dairy cattle were lighter muscled, yet fatter than the dairy cattle surveyed in 2007. Of cattle surveyed, most did not have horns, nor any visible live animal defects. Unbranded hides were observed on 77.3% of cattle. Carcass bruising was seen on 64.1% of cow carcasses and 42.9% of bull carcasses. However, over half of all bruises were identified to only be minor in severity. Nearly all cattle (98.4%) were free of visible injection-site lesions. Current results suggest improvements have been made in cattle and meat quality in the cow and bull sector. Furthermore, the results provide guidance for continued educational and research efforts for improving market cow and bull beef quality.

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