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1.
Clin Neurophysiol ; 130(8): 1243-1252, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31163369

RESUMO

OBJECTIVE: Neuroimaging studies of hematologic cancer patients report altered activity in dorsal attention and central executive networks. To determine the consequences of these altered brain networks, we evaluated neurophysiological correlates of attention and working memory in hematologic cancer patients prior to initiating treatment. METHODS: Hematologic cancer patients (19-80 years) were excluded for premorbid cognitive impairment, prior non-hematologic cancer diagnosis, and prior chemotherapy. Attention was manipulated by presenting an irrelevant spatial cue prior to visual search displays. Working memory was manipulated by presenting irrelevant distractors within memory displays. Electroencephalogram was recorded during task performance. RESULTS: Patients (n = 28) and controls (n = 15) were balanced on age, gender, and education. Spatial cues evoked larger N2pc amplitudes, a correlate of spatial attention, in patients than controls (p < .05; Cohen's d > 0.7). Memory distractors evoked larger contralateral delay activity amplitudes, a correlate of working memory load, in patients (p = .028; Cohen's d = 1.1) but not controls (p = .64). CONCLUSIONS: Prior to initiating treatment, hematologic cancer patients demonstrated poor control over spatial attention and working memory, consistent with altered dorsal attention and central executive network activity. SIGNIFICANCE: Hematologic cancer patients may be at a higher risk for selecting, processing, and storing distracting information that would compete with more immediate goal-related behaviors.


Assuntos
Atenção , Encéfalo/fisiopatologia , Eletroencefalografia , Neoplasias Hematológicas/fisiopatologia , Memória de Curto Prazo , Adulto , Idoso , Feminino , Neoplasias Hematológicas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
2.
Eur Cell Mater ; 31: 425-39, 2016 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-27341301

RESUMO

Mesenchymal stem cells (MSCs) have been considered as a potential source for cell-based therapies in arthritic diseases for both their chondrogenic and anti-inflammatory properties. Thus, we examined how MSC-based neocartilage responds to tumour necrosis factor alpha (TNF-α) compared to articular chondrocyte (AC)-based neocartilage. Since oxygen tension is altered in arthritic joints, we also examined how increased oxygen tension influences this process. Monolayer-expanded healthy human ACs and bone marrow MSCs were cultured in chondrogenic medium in three-dimensional culture under hypoxia. They were then exposed to TNF-α under hypoxic or increased oxygen tension. We found no inherent anti-inflammatory potential of MSC-derived neocartilage as it pertains to the enzymes studied here: more degradative enzymes were upregulated by TNF-α in MSCs than in ACs, regardless of the oxygen tension. MSCs were also more sensitive to reoxygenation during TNF-α exposure, as indicated by increased proteoglycan loss, increased aggrecanase-generated metabolites, and further upregulation of the major aggrecanases, ADAMTS4 and ADAMTS5. There was also evidence of matrix metalloproteinase (MMP)-mediated aggrecan interglobular domain cleavage and type II collagen loss in response to TNF-α in both MSCs and ACs, but more MMPs were further upregulated by reoxygenation in MSCs than in ACs. Our study provides further evidence that consideration of oxygen tension is essential for studying cartilage degradation; for example, neocartilage produced from MSCs may be more sensitive to the negative effects of repeated hypoxia/reoxygenation events than AC-derived neocartilage. Consideration of the differences in responses may be important for cell-based therapies and selection of adjunctive chondroprotective agents.


Assuntos
Condrogênese/efeitos dos fármacos , Matriz Extracelular/metabolismo , Oxigênio/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Cartilagem Articular/citologia , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Matriz Extracelular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinases da Matriz/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Proteoglicanas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
3.
Reprod Domest Anim ; 51(2): 287-93, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26939713

RESUMO

This study was designed to test the hypothesis that sperm-bound IgG and IgA decrease binding of bull spermatozoa to oviductal epithelial cells in vitro. Three ejaculates were cryopreserved from each of four antisperm antibody (ASA)-negative satisfactory breeder bulls. Bulls were then immunized with autologous spermatozoa, and three ASA-positive ejaculates were cryopreserved from each bull post-immunization. First, microscopy methods were compared to select the most appropriate assay for evaluation of oviductal binding index (BI). The BI did not differ when the evaluation was performed under fluorescence microscopy (131.1 sperm/mm(2); 62.5-251.1 sperm/mm(2)), phase-contrast microscopy (160.5 sperm/mm(2); 56.8-397.4 mm(2)) or their combination (116.4 sperm/mm(2); 56.8-249.6 sperm/mm(2)) (Median; IQR). The combination of microscopy methods was selected as it allowed better visualization of cells. Then, BI was compared between ASA-negative and ASA-positive ejaculates, and the association between BI and ASA binding was evaluated. The BI was less in ASA-positive (114.9; 0 to 201.8 sperm/0.1 mm(2)) than ASA-negative samples (218.9; 24.7 to 276.8 sperm/0.1 mm(2)) (P = 0.0002). This reduction in BI was significant in three of the four bulls. Regression analysis identified a negative association between BI and the percentage of IgG-bound (p = 0.013) but not IgA-bound spermatozoa. In conclusion, sperm-bound IgG decreased the ability of bovine spermatozoa to bind to oviductal epithelial cells in vitro.


Assuntos
Bovinos/fisiologia , Adesão Celular/fisiologia , Imunoglobulina A/fisiologia , Imunoglobulina G/fisiologia , Oviductos/citologia , Espermatozoides/fisiologia , Animais , Células Epiteliais/fisiologia , Feminino , Masculino
4.
J Vet Intern Med ; 25(3): 598-604, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21418323

RESUMO

BACKGROUND: Parenteral nutrition is an important method of nutritional support in hospitalized animals, but minimal information has been published on its use in camelids. HYPOTHESIS/OBJECTIVES: The purpose of this study was to characterize the use of total parenteral nutrition (TPN) in alpacas, evaluate the formulations used, and determine potential complications. ANIMALS: Twenty-two alpacas hospitalized at the Tufts Cummings School for Veterinary Medicine (site 1: n = 8) and the Ohio State University Veterinary Teaching Hospital (site 2: n = 14). METHODS: A retrospective analysis of all alpacas that received TPN between 2002 and 2008 was performed to assess clinical indications, clinical and clinicopathologic data, and outcome. RESULTS: The most common underlying diseases in animals receiving TPN were gastrointestinal dysfunction (n = 16), hepatic disease (n = 2), and neoplasia (n = 2). Several metabolic abnormalities were identified in animals (n = 20/22) before TPN was initiated, including lipemia (n = 12/22), hyperglycemia (11/22), and hypokalemia (n = 11/22). Median age was significantly lower for site 1 cases (0.1 years; range, 0.01-11.0) compared with those from site 2 (4.9 years; range, 0.1-13.7; P = .03). Animals at site 2 also had a longer duration of hospitalization (P = .01) and TPN administration (P = .004), as well as higher survival rate (P < .02). Twenty-one of 22 alpacas developed at least 1 complication during TPN administration. Metabolic complications were most prevalent (n = 21/22) and included hyperglycemia (n = 8/21), lipemia (n = 7/21), hypokalemia (n = 3/21), and refeeding syndrome (n = 3/21). CONCLUSIONS AND CLINICAL IMPORTANCE: TPN is a feasible method of nutritional support for alpacas when enteral feeding is not possible. Prospective studies are warranted to determine optimal TPN formulations for alpacas.


Assuntos
Camelídeos Americanos , Gastroenteropatias/veterinária , Hepatopatias/veterinária , Neoplasias/veterinária , Nutrição Parenteral Total/veterinária , Animais , Gastroenteropatias/terapia , Hepatopatias/terapia , Neoplasias/terapia , Estudos Retrospectivos
5.
Aust Vet J ; 88(1-2): 39-44, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20148826

RESUMO

OBJECTIVE: This retrospective study was conducted to evaluate the outcome for cattle with diaphyseal fractures of the femur, but not including capital physeal injuries. METHODS: Sources of information were medical records of cattle having a definitive diagnosis of diaphyseal femoral fractures and telephone survey of owners. RESULTS: Medical records for 26 cattle with femoral fracture were found; of the 20 aged less than 2 months, 15 were treated surgically, 4 conservatively (stall rest) and 1 was euthanased without treatment. The surgical treatment varied according to the configuration of the fracture and the surgeon's experience. Surgery for mid-diaphyseal fractures had a significantly better surgical outcome then distal diaphyseal fractures (P < 0.05), as there were significantly fewer postoperative complications. Of the 15 calves treated surgically, 10 were discharged from hospital and 5 were retained in the herd without noticeable lameness. Of the 4 calves treated conservatively, 3 were alive at follow-up, but 2 were still lame. Of the 6 older cattle, 3 were euthanased without treatment and 3 were treated conservatively, 2 of which were alive at follow-up but 1 was still lame. CONCLUSION: Conservative treatment of femur fracture in cattle is possible but associated with complications during the convalescence. Continued research is needed to optimise distal diaphyseal fracture stabilisation in young cattle.


Assuntos
Bovinos/lesões , Bovinos/cirurgia , Fraturas do Fêmur/veterinária , Animais , Diáfises/lesões , Diáfises/cirurgia , Feminino , Fraturas do Fêmur/mortalidade , Fraturas do Fêmur/cirurgia , Seguimentos , Fixação de Fratura/veterinária , Consolidação da Fratura , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/veterinária , Descanso , Estudos Retrospectivos , Resultado do Tratamento
6.
Viral Immunol ; 18(4): 637-48, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16359230

RESUMO

Current treatments for hepatitis C infection have limited efficacy, and there is no vaccine available. The goal of this study was to compare the immune response to several immunization combinations against hepatitis C virus (HCV). Six groups of mice were immunized at weeks 0, 4, and 8 with different combinations of a candidate HCV vaccine consisting of 100 microg recombinant HCV core/E1/E2 (rHCV) DNA plasmid and/or 25 microg rHCV polyprotein and 50 microL Montanide ISA- 51. Four weeks after the last injection, all groups of mice were sacrificed and blood samples and spleens were collected for measuring the levels of specific HCV antibodies (total IgG, IgG1, and IgG2a). Cell proliferation and intracellular interferon-gamma were also measured. Among the groups of immunized mice, only the mice immunized with rHCV DNA plasmid, rHCV polyprotein, and montanide (group D) and mice immunized with rHCV polyprotein and montanide (group F) demonstrated a significant increase in the total IgG titer after immunization. IgG1 was the predominant antibody detected in both groups D and F. No IgG2a was detected in any of the groups. Proliferation assays demonstrated that splenocytes from group D and group C (rHCV DNA primed/rHCV polyprotein boost) developed significant anti-HCV proliferative responses. The combination of an rHCV DNA plasmid, rHCV polyprotein, and montanide induced a high antibody titer with a predominance of IgG1 antibodies and recognized the major neutralization epitopes in HVR1. In contrast, group C did not show an increase in anti-HCV antibodies, but did show a proliferative response.


Assuntos
Anticorpos Anti-Hepatite C/imunologia , Hepatite C/prevenção & controle , Vacinas contra Hepatite Viral/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Proliferação de Células , Epitopos/imunologia , Anticorpos Anti-Hepatite C/sangue , Imunoglobulina G/sangue , Injeções Intramusculares , Interferon gama/análise , Interleucina-5/sangue , Masculino , Manitol/administração & dosagem , Manitol/análogos & derivados , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Testes de Neutralização , Ácidos Oleicos/administração & dosagem , Linfócitos T/imunologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Proteínas do Core Viral/genética , Proteínas do Core Viral/imunologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Vacinas contra Hepatite Viral/administração & dosagem
7.
J Postgrad Med ; 49(3): 222-8, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14597785

RESUMO

India is a developing country with one of the most diverse populations and diets in the world. Cancer rates in India are lower than those seen in Western countries, but are rising with increasing migration of rural population to the cities, increase in life expectancy and changes in lifestyles. In India, rates for oral and oesophageal cancers are some of the highest in the world. In contrast, the rates for colorectal, prostate, and lung cancers are one of the lowest. Studies of Indian immigrants in Western societies indicate that rates of cancer and other chronic diseases, such as coronary heart disease and diabetes, increase dramatically after a generation in the adopted country. Change of diet is among the factors that may be responsible for the changing disease rates. Diet in India encompasses diversity unknown to most other countries, with many dietary patterns emanating from cultural and religious teachings that have existed for thousands of years. Very little is known, however, about the role of the Indian diet in causation of cancer or its role, if any, in prevention of cancer, although more attention is being focused on certain aspects of the Indian diet, such as vegetarianism, spices, and food additives. Of particular interest for cancer prevention is the role of turmeric (curcumin), an ingredient in common Indian curry spice. Researchers also have investigated cumin, chilies, kalakhar, Amrita Bindu, and various plant seeds for their apparent cancer preventive properties. Few prospective studies, however, have been conducted to investigate the role of Indian diet and its various components in prevention of cancer. From a public health perspective, there is an increasing need to develop cancer prevention programs responsive to the unique diets and cultural practices of the people of India.


Assuntos
Dieta , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Humanos , Incidência , Índia/epidemiologia , Fatores de Risco
8.
J Immunol ; 167(10): 5669-77, 2001 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11698439

RESUMO

Traditionally, emphasis has been placed on the roles of Th cells in generating and amplifying both cellular and humoral memory responses. Little is known about the potential contributions of B cell subsets to immunological memory. Resting memory B cells have generally been regarded as poor APC, attributed in part to the relative paucity of costimulatory molecules identified on their surface. We describe a novel subpopulation of human memory B cells that express CD80 in their resting state, are poised to secrete particularly large amounts of class switched Igs, and can efficiently present Ag to and activate T cells. This functionally distinct B cell subset may represent an important mechanism by which quiescent human B cells can initiate and propagate rapid and vigorous immune memory responses. Finally, these studies extend recent observations in the murine system and highlight the phenotypic and functional diversity that exists within the human B cell memory compartment.


Assuntos
Linfócitos B/imunologia , Antígeno B7-1/metabolismo , Memória Imunológica , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Apresentação de Antígeno , Subpopulações de Linfócitos B/classificação , Células Cultivadas , Humanos , Imunoglobulinas/biossíntese , Imunofenotipagem , Cinética , Ativação Linfocitária , Linfócitos T/imunologia
9.
Am J Hypertens ; 14(8 Pt 1): 761-7, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11497191

RESUMO

Previous studies have shown that high end-tidal CO2 (PetCO2) is a marker for sodium sensitivity of blood pressure (BP) in White Americans, and that the BP of African Americans is more sensitive to high sodium intake than that of whites. The present study tested the hypothesis that resting PetCO2 is higher in normotensive African Americans than in whites. Resting end-tidal CO2 of 395 white and 125 African American participants in the Baltimore Longitudinal Study on Aging was monitored for 20 min with a respiratory gas monitor, and BP and heart rate were recorded every 5 min by oscillometric methodology. Twenty-four-hour urinary excretion of a circulating sodium pump inhibitor marinobufagenin-like compound (MBG), which increases when plasma volume is expanded, was also analyzed by fluoroimmunoassay in racial groups. Mean resting PetCO2 of African American men was higher than that of white men (38.1+/-0.5 v 36.4+/-0.3 mm Hg), and resting PetCO2 of African American women was higher than that of white women (37.7+/-0.3 v 36.2+/-0.3 mm Hg). The differences were not significant in either men or women less than 50 years old, but were substantial in both men and women more than 50 years. Twenty-four-hour urinary excretion of MBG was higher in white (2.7+/-0.2 pmol) than in African American (2.1+/-0.2 pmol) participants, and high PetCO2 was a significant independent predictor of high MBG excretion in African Americans. These data are consistent with the hypothesis that the higher resting PetCO2 in African Americans plays a role in slower urinary excretion of sodium, greater BP sensitivity to high sodium intake, and increased prevalence of chronic hypertension.


Assuntos
Bufanolídeos/urina , Dióxido de Carbono/sangue , Hipertensão/sangue , Hipertensão/etnologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Distribuição por Idade , População Negra , Pressão Sanguínea , Volume Sanguíneo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Distribuição por Sexo , Sódio/farmacocinética , População Branca
10.
EMBO J ; 20(12): 3238-50, 2001 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-11406600

RESUMO

Structural maintenance of chromosomes (SMC) proteins play fundamental roles in higher-order chromosome dynamics from bacteria to humans. It has been proposed that the Bacillus subtilis SMC (BsSMC) homodimer is composed of two anti-parallel coiled-coil arms, each having an ATP-binding domain at its distal end. It remains totally unknown, however, how the two-armed structure supports ATP-dependent actions of BsSMC. By constructing a number of mutant derivatives including 'single-armed' BsSMC, we show here that the central hinge domain provides a structural flexibility that allows opening and closing of the two arms. This unique structure brings about bimodal regulation of the SMC ATPase cycle. Closing the arm can trigger ATP hydrolysis by allowing an end-end interaction within a dimer (intramolecular mode). When bound to DNA, ATP promotes a dimer-dimer interaction, which in turn activates their DNA-dependent ATPase activity (intermolecular mode). Our results reveal a novel mechanism of ATPase regulation and provide mechanistic insights into how eukaryotic SMC protein complexes could mediate diverse chromosomal functions, such as chromosome condensation and sister chromatid cohesion.


Assuntos
Adenosina Trifosfatases/metabolismo , Bacillus subtilis/enzimologia , Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Nucleares/metabolismo , Adenosina Trifosfatases/genética , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Animais , Bacillus subtilis/genética , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Ativação Enzimática , Microscopia Eletrônica , Dados de Sequência Molecular , Mutagênese , Proteínas Nucleares/genética
11.
Am J Physiol Regul Integr Comp Physiol ; 281(1): R352-8, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11404312

RESUMO

Our study investigated the hypothesis that the combination of a high NaCl diet and social isolation stress would increase systolic blood pressure (SBP) and endogenous sodium pump ligands (SPL), ouabainlike compound (OLC), and marinobufagenin (MBG). Excretion of MBG and OLC, SBP, and organ weights were studied in four groups (n = 8) of male Fisher 344 x Norwegian brown rats: controls, socially isolated (Iso), 4% NaCl diet (Salt), and the combination of Salt and Iso (Iso+Salt). In Salt, MBG excretion increased by 78% (P < 0.01), whereas SBP and OLC remained unchanged. In Iso, SBP and MBG did not change, but OLC peaked on day 1. In the Iso+Salt, SBP increased by 9 mmHg, MBG excretion increased (42.0 +/- 7.6 vs. 10.0 +/- 1.5 pmol/24 h, P < 0.01), whereas OLC peaked at day 1 (25.0 +/- 2.5 vs. 10.0 +/- 2.0 pmol/24 h, P < 0.01) and remained elevated. Heart and kidney weights were increased in Salt and Iso+Salt. Aortic weights were increased in Iso and Iso+Salt. Thus a high NaCl intake stimulates MBG excretion, whereas isolation stress stimulates OLC. The combination of Salt and Iso is accompanied by marked stimulation of both SPL.


Assuntos
Bufanolídeos/urina , Digoxina , Saponinas/urina , Isolamento Social , Cloreto de Sódio na Dieta/farmacocinética , ATPase Trocadora de Sódio-Potássio/metabolismo , Estresse Psicológico/metabolismo , Animais , Cardenolídeos , Ingestão de Líquidos/fisiologia , Ingestão de Alimentos/fisiologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Natriurese/fisiologia , Tamanho do Órgão , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos F344 , Urina
12.
Vet Clin North Am Food Anim Pract ; 17(1): 143-58, vii, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11320692

RESUMO

Digital diseases are commonly seen in cattle. Cattle affected by digital disorders do not always respond to conservative therapy and require surgery. Surgical procedures for the common digital disorders are described, with emphasis on the different approaches to the distal interphalangeal joint.


Assuntos
Artrite Infecciosa/veterinária , Doenças dos Bovinos/cirurgia , Doenças do Pé/veterinária , Casco e Garras , Coxeadura Animal/cirurgia , Amputação Cirúrgica/veterinária , Animais , Anquilose/cirurgia , Anquilose/veterinária , Artrite Infecciosa/cirurgia , Bovinos , Doenças do Pé/cirurgia , Tenossinovite/cirurgia , Tenossinovite/veterinária
13.
Protein Eng ; 14(12): 993-1000, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11809930

RESUMO

Because of its stringent sequence specificity, the catalytic domain of the nuclear inclusion protease from tobacco etch virus (TEV) is a useful reagent for cleaving genetically engineered fusion proteins. However, a serious drawback of TEV protease is that it readily cleaves itself at a specific site to generate a truncated enzyme with greatly diminished activity. The rate of autoinactivation is proportional to the concentration of TEV protease, implying a bimolecular reaction mechanism. Yet, a catalytically active protease was unable to convert a catalytically inactive protease into the truncated form. Adding increasing concentrations of the catalytically inactive protease to a fixed amount of the wild-type enzyme accelerated its rate of autoinactivation. Taken together, these results suggest that autoinactivation of TEV protease may be an intramolecular reaction that is facilitated by an allosteric interaction between protease molecules. In an effort to create a more stable protease, we made amino acid substitutions in the P2 and P1' positions of the internal cleavage site and assessed their impact on the enzyme's stability and catalytic activity. One of the P1' mutants, S219V, was not only far more stable than the wild-type protease (approximately 100-fold), but also a more efficient catalyst.


Assuntos
Endopeptidases/química , Sequência de Aminoácidos , Catálise , Domínio Catalítico , Endopeptidases/genética , Endopeptidases/fisiologia , Estabilidade Enzimática , Cinética , Dados de Sequência Molecular , Mutação , Engenharia de Proteínas , Alinhamento de Sequência
14.
Nutr Cancer ; 41(1-2): 1-16, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-12094610

RESUMO

Dietary nutrients can influence cancer risk by inhibiting or enhancing carcinogenesis through diverse mechanisms of action. The identification and elucidation of their sites of action have been a focus of nutrition and cancer research for more than four decades. Transforming nutrition and cancer research from a predominantly observational to a molecular approach offers exciting opportunities for truly identifying those who will and will not benefit from dietary intervention strategies. The emerging field of nutritional genomics, defined here as the study of any genetic or epigenetic interaction with a nutrient, will be key to this evolution. Unraveling which genetic upregulation or downregulation leads to subsequent phenotype changes will not be easy. There is evidence that genetic polymorphisms can influence the dynamics between nutrients and molecular targets and, thus, contribute to variation in response among individuals. Because many molecular targets will likely be identified, it may be necessary to credential nutrients, that is, to determine which specific nutrient-related genetic and epigenetic changes bring about phenotypic changes, to establish which interactions are the most important and under what circumstances. Vitamin D, calcium, folate, selenium, genistein, and resveratrol are highlighted, because they represent specific classes of nutrients and illustrate the need to credential various nutrients to understand their physiological significance in cancer prevention. As the science of nutrition unfolds, a clearer understanding will emerge about how nutrients can modulate cancer risk through molecular interactions and how foods might be changed by agronomic approaches and/or biotechnology. Undeniably, embracing new genomic technologies offers exciting opportunities for advances in the broad area of nutrition, especially those related to cancer prevention.


Assuntos
Dieta , Neoplasias/genética , Neoplasias/prevenção & controle , Fenômenos Fisiológicos da Nutrição , Anticarcinógenos , Cálcio , Ácido Fólico , Tecnologia de Alimentos , Genisteína , Humanos , Polimorfismo Genético , Resveratrol , Selênio , Estilbenos , Vitamina D
15.
Contemp Top Lab Anim Sci ; 39(5): 26-8, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11040871

RESUMO

The purpose of our study was to develop a surgical method for collection of ileal digesta in neonatal (< 5 kg) pigs and to determine potential complications of the procedure. In 18 10-day-old pigs, we performed ileocutaneous anastomosis (ICA) via a right ventrolateral incision. The ICA was readily performed in these neonatal pigs; one pig died 24 hours after surgery because of intestinal volvulus. Pigs were monitored twice daily for development of post-operative complications. Ileal digesta were collected "free-catch" by using metabolism cages because attempts to use cannulas (diameter, 4 to 8 mm) and collection bags failed. To determine the effect of colon bypass on hydration, electrolytes, glucose, and serum enzyme activities, we collected serum biochemistry data before and 6 days after surgery. Changes in serum biochemical values included increased potassium, creatinine, total protein, albumin, and globulin and decreased ALP and glucose, but all values remained within normal ranges for neonatal pigs. ICA is tolerated well by neonatal pigs and is an easily learned and rapid technique for collection of ileal digesta. In addition, ICA is a useful alternative to "T-cannulas" and ileorectal anastomosis for nutrition research using neonatal pigs weighing < 5 kg.


Assuntos
Íleo/cirurgia , Suínos/cirurgia , Fosfatase Alcalina/sangue , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/veterinária , Animais , Animais Recém-Nascidos , Glicemia/análise , Proteínas Sanguíneas/análise , Creatinina/sangue , Conteúdo Gastrointestinal/química , Potássio/sangue , Albumina Sérica/análise , Soroglobulinas/análise , Suínos/sangue
16.
Vet Surg ; 29(4): 341-6, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10917284

RESUMO

OBJECTIVE: To compare synovial fluid characteristics of cattle with infectious and noninfectious arthritis. STUDY DESIGN: Retrospective cohort study. ANIMAL OR SAMPLE POPULATION: 130 cattle. METHODS: Synovial fluid was analyzed for total nucleated cell count (NCC), absolute number and percentages of polymorphonuclear (PMN) and mononuclear cells, total protein (TP) concentration, and specific gravity. Cattle were categorized as having infectious or noninfectious arthritis based on physical and lameness examinations, joint radiographs, and microbial culture results. Kruskal-Wallis 1-way analysis of variance was used to compare synovial fluid analysis data from different categories. Selection of cut-off values for the calculation of likelihood ratios, sensitivity, specificity, and positive and negative predictive values was based on examination of the distribution of the data using histograms. RESULTS: Cattle with infectious arthritis had significantly higher numbers of total NNC, PMN cells, TP concentration, and specific gravity (P = .0001) and a significantly higher percentage of PMN cells compared with cattle with noninfectious arthritis (P = .0001). The percentage of mononuclear cells was significantly higher in cattle with noninfectious arthritis (P = .0001). CONCLUSIONS: Synovial fluid analysis is useful for differentiation of infectious and noninfectious causes of joint disease in cattle. CLINICAL RELEVANCE: Cattle with a synovial fluid total NCC > 25,000 cells/microL, a PMN cell count > 20,000 cells/microL or more than 80% PMN cells, and TP > 4.5 g/dL should be considered to have infectious arthritis.


Assuntos
Artrite Infecciosa/veterinária , Doenças dos Bovinos/diagnóstico , Líquido Sinovial/citologia , Animais , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/patologia , Bovinos , Doenças dos Bovinos/patologia , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Coxeadura Animal , Contagem de Leucócitos/veterinária , Masculino , Registros/veterinária , Estudos Retrospectivos
17.
Am J Vet Res ; 61(5): 537-43, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10803649

RESUMO

OBJECTIVE: To determine the effects of phenylbutazone (PBZ) on bone activity and bone formation in horses. ANIMALS: 12 healthy 1- to 2-year-old horses. PROCEDURES: Biopsy was performed to obtain unicortical bone specimens from 1 tibia on day 0 and from the contralateral tibia on day 14. Fluorochromic markers were administered IV 2 days prior to and on days 0, 10, 15, and 25 after biopsy was performed. Six horses received PBZ (4.4 mg/kg of body weight, PO, q 12 h) and 6 horses were used as controls. All horses were euthanatized on day 30 and tissues from biopsy sites, with adjacent cortical bone, were collected. Osteonal density and activity, mineral apposition rate (MAR), and percentage of mineralized tissue filling the biopsy-induced defects in cortical bone were assessed. Serum samples from all horses were analyzed for bone-specific alkaline phosphatase activity and concentration of PBZ. RESULTS: MAR was significantly decreased in horses treated with PBZ. Regional acceleratory phenomenon was observed in cortical bone in both groups but was significantly decreased in horses treated with PBZ. Osteonal activity was similar at all time points in all horses. In control horses, percentage of mineralized tissue filling the cortical defects was significantly greater in defects present for 30 days, compared with defects present for 14 days. Differences in percentage of mineralized tissue were not detected in horses treated with PBZ. CONCLUSIONS AND CLINICAL RELEVANCE: PBZ decreased MAR in cortical bone and appeared to decrease healing rate of cortical defects in horses.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Consolidação da Fratura/efeitos dos fármacos , Doenças dos Cavalos/tratamento farmacológico , Fenilbutazona/farmacologia , Fosfatase Alcalina/sangue , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Biópsia/veterinária , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/veterinária , Feminino , Fluoresceínas/química , Corantes Fluorescentes/química , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/cirurgia , Fraturas Ósseas/veterinária , Ósteon/patologia , Cavalos , Processamento de Imagem Assistida por Computador , Imunoensaio/veterinária , Masculino , Oxitetraciclina/química , Fenilbutazona/sangue , Fenilbutazona/uso terapêutico , Antagonistas de Prostaglandina/farmacologia , Antagonistas de Prostaglandina/uso terapêutico , Distribuição Aleatória , Tíbia/patologia , Tíbia/fisiologia
18.
Nat Med ; 6(2): 211-4, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10655112

RESUMO

T-cell co-stimulation delivered by the molecules B7-1 or B7-2 through CD28 has a positive effect on T-cell activation, whereas engagement of cytotoxic T-lymphocyte antigen 4 (CTLA-4) by these molecules inhibits activation. In vivo administration to mice of blocking monoclonal antibodies or Fab fragments against CTLA-4 can augment antigen-specific T-cell responses and, thus, therapy with monoclonal antibody against CTLA-4 has potential applications for tumor therapy and enhancement of vaccine immunization. The effects of B7-1 and B7-2 co-stimulation through CD28 depend on the strength of the signal delivered through the T-cell receptor (TCR) and the activation state of T cells during activation. Thus, we sought to determine whether these factors similarly influence the effect of B7-mediated signals delivered through CTLA-4 during T-cell activation. Using freshly isolated human T cells and Fab fragments of a monoclonal antibody against CTLA-4, we demonstrate here that CTLA-4 blockade can enhance or inhibit the clonal expansion of different T cells that respond to the same antigen, depending on both the T-cell activation state and the strength of the T-cell receptor signal delivered during T-cell stimulation. Thus, for whole T-cell populations, blocking a negative signal may paradoxically inhibit immune responses. These results provide a theoretical framework for clinical trials in which co-stimulatory signals are manipulated in an attempt to modulate the immune response in human disease.


Assuntos
Anticorpos Monoclonais/imunologia , Antígenos de Diferenciação/imunologia , Imunoconjugados , Linfócitos T/imunologia , Abatacepte , Animais , Antígenos CD , Células CHO , Antígeno CTLA-4 , Cricetinae , Ensaio de Imunoadsorção Enzimática , Humanos , Técnicas In Vitro , Ativação Linfocitária , Linfócitos T/citologia
19.
Virology ; 268(1): 94-103, 2000 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10683331

RESUMO

Development of an effective preventive or therapeutic vaccine against HIV-1 is an important goal in the fight against AIDS. Effective virus clearance and inhibition of spread to target organs depends principally on the cellular immune response. Therefore, a vaccine against HIV-1 should elicit virus-specific cytotoxic lymphocyte (CTL) responses to eliminate the virus during the cell-associated stages of its life cycle. The vaccine should also be capable of inducing immunity at the mucosal surfaces, the primary route of transmission. Recombinant Bacille Calmette-Guérin (BCG) expressing viral proteins offers an excellent candidate vaccine in view of its safety and ability to persist intracellularly, resulting in the induction of long-lasting immunity and stimulation of the cellular immune response. BCG can be administered orally to induce HIV-specific immunity at the mucosal surfaces. The immunogenicity of four recombinant BCG constructs expressing simian immunodeficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques. A single simultaneous inoculation of all four recombinants elicited SIV-specific IgA and IgG antibody, and cellular immune responses, including CTL and helper T cell proliferation. Our results demonstrate that BCG recombinant vectors can induce concomitant humoral and cellular immune responses to the major proteins of SIV.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra a SAIDS/imunologia , Vírus da Imunodeficiência Símia/imunologia , Linfócitos T Citotóxicos/imunologia , Vacinas Sintéticas/imunologia , Proteínas Virais/imunologia , Animais , Vacina BCG/genética , Vacina BCG/imunologia , Western Blotting , Clonagem Molecular , Citotoxicidade Imunológica , Produtos do Gene env/genética , Produtos do Gene env/imunologia , Produtos do Gene env/metabolismo , Produtos do Gene gag/genética , Produtos do Gene gag/imunologia , Produtos do Gene gag/metabolismo , Produtos do Gene nef/genética , Produtos do Gene nef/imunologia , Produtos do Gene nef/metabolismo , Produtos do Gene pol/genética , Produtos do Gene pol/imunologia , Produtos do Gene pol/metabolismo , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Ativação Linfocitária , Macaca mulatta , Vacinas contra a SAIDS/genética , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/metabolismo , Vacinação , Vacinas Sintéticas/genética , Proteínas Virais/genética , Proteínas Virais/metabolismo
20.
Vet Clin North Am Equine Pract ; 16(2): 363-75, vii, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14983913

RESUMO

The minimally invasive nature of laparoscopic techniques and shorter convalescent periods have made these techniques increasingly popular for use in New World camelids (llamas and alpacas). This article outlines the instruments and steps needed to perform laparoscopic surgery on the female reproductive tract in llamas and alpacas.


Assuntos
Camelídeos Americanos/cirurgia , Histerectomia/veterinária , Laparoscopia/veterinária , Ovariectomia/veterinária , Animais , Feminino , Histerectomia/instrumentação , Histerectomia/métodos , Laparoscópios/veterinária , Laparoscopia/métodos , Ovariectomia/instrumentação , Ovariectomia/métodos , Postura
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