RESUMO
We assessed the performance of hermetic triple layer Purdue Improved Crop Storage (PICS) bags for protecting Hibiscus sabdariffa grain against storage insects. The major storage pest in the grain was a bruchid, Spermophagus sp.. When we stored infested H. sabdariffa grain for six months in the woven polypropylene bags typically used by farmers, the Spermophagus population increased 33-fold over that initially present. The mean number of emergence holes per 100 seeds increased from 3.3 holes to 35.4 holes during this time period, while grain held for the same length of time in PICS bags experienced no increase in the numbers of holes. Grain weight loss in the woven control bags was 8.6% while no weight loss was observed in the PICS bags. Seed germination rates of grain held in woven bags for six months dropped significantly while germination of grain held in PICS bags did not change from the initial value. PICS bags can be used to safely store Hibiscus grain after harvest to protect against a major insect pest.
RESUMO
Over the past decade, the robotic assisted radical prostatectomy (RARP) has grown increasingly popular and quickly equated itself as the most commonly used modality to treat locally-confined prostate cancer. Despite increased utilization, there is limited comparative research demonstrating superiority for RARP over the conventional radical retropubic prostatectomy (RRP). Furthermore, though perioperative and short-term oncologic outcomes are equivalent if not superior for the robotic approach, the optimal utilization of robotic technology remains to be determined with cost serving as a primary driver. In this review, we performed a literature search to identify comparative effectiveness research as it pertains to RARP versus RRP. We performed a PubMed literature search for a review of articles published between 2000 and 2014 using the following keywords to identify pertinent research: "robot or robotic prostatectomy", "open or retropubic prostatectomy", "cost", "resource utilization". Long-term data comparing RARP and RRP remains limited, though short-term positive surgical margins, biochemical recurrence-free survival, and need for adjuvant therapy appear at least equivocal, if not in favor of RARP versus RRP. Functional outcomes including return of continence and potency favor RARP while cost still favors RRP. Nonetheless, the generalization of results remains difficult with surgeon volume playing a large role in improving efficiency and quality. For the foreseeable future, an increasing number of prostatectomies will continue to be performed robotically. Though RARP appears to offer improved functional outcomes with good short-term oncologic outcomes, there is a need for longer-term studies to assess the true value of RARP. Outcomes aside, rigorous, prospective randomized-controlled trials must also be performed on the cost-effectiveness of RARP to determine its overall utility in an era of health care delivery reform.
Assuntos
Prostatectomia/economia , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/economia , Análise Custo-Benefício , Medicina Baseada em Evidências , Humanos , Los Angeles , Masculino , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/normas , Resultado do TratamentoRESUMO
Bacillus Calmette-Guerin (BCG) remains the only FDA-approved first-line therapy in patients with high-risk non-muscle invasive bladder cancer. Recurrences, even after adequate BCG therapy, are common and the efficacy of second-line therapies remains modest. Therefore, early identification of patients likely to recur and treatment after recurrence remain critical unmet needs in the clinical care of bladder cancer patients. To address these deficits, a better understanding of the mechanisms of resistance to BCG-therapy is needed. The virtual update of the International Bladder Cancer Network (IBCN) on the biology of response to BCG focused on potential mechanisms and markers of resistance to intravesical BCG therapy. The insights from this meeting will be highlighted and put into context of previously reported mechanisms of resistance to BCG in this review.
Assuntos
Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Imunoterapia , Administração Intravesical , Neoplasias da Bexiga Urinária/tratamento farmacológico , Biologia , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
PURPOSE: Percent of embryonal carcinoma and lymphovascular invasion in the primary tumor are risk factors for occult retroperitoneal metastatic disease. High risk patients with clinical stage I and IIA nonseminomatous germ cell tumor who underwent primary retroperitoneal lymph node dissection were identified to discern any other risk factors for metastatic disease. MATERIALS AND METHODS: Patients who had undergone retroperitoneal lymph node dissection at our institution from 1993 to 2009 were identified and clinical charts were reviewed. A total of 90 patients with orchiectomy specimens containing more than 30% embryonal carcinoma who underwent primary retroperitoneal lymph node dissection were identified and perioperative data were obtained. RESULTS: Of 353 patients 90 (25%) had greater than 30% embryonal carcinoma and underwent primary retroperitoneal lymph node dissection. Of these patients 45 (50%) had lymphovascular invasion. Median followup was 1.1 years. Positive lymph nodes identified at retroperitoneal lymph node dissection were noted in 30 (46%) and 15 (60%) patients with clinical stage I vs clinical stage II disease. On multivariate analysis embryonal carcinoma (OR 1.02, 95% CI 1.00-1.04) and lymphovascular invasion (OR 3.52, 95% CI 1.43-8.67) were associated with positive lymph nodes at retroperitoneal lymph node dissection. The positive predictive value for 100% embryonal carcinoma was 65.5%, although the negative predictive value for 30% embryonal carcinoma was 85.7%. CONCLUSIONS: Embryonal carcinoma and lymphovascular invasion were significantly and independently associated with the risk of occult retroperitoneal metastatic disease. These results should be considered when counseling patients about appropriate treatment options.
Assuntos
Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Testiculares/patologia , Adulto , Humanos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/cirurgia , Valor Preditivo dos Testes , Espaço Retroperitoneal , Fatores de Risco , Neoplasias Testiculares/cirurgiaRESUMO
The ß-, γ- and δ-kafirin genes were sequenced from 35 Sorghum genotypes to investigate the allelic diversity of seed storage proteins. A range of grain sorghums, including inbred parents from internationally diverse breeding programs and landraces, and three wild Sorghum relatives were selected to encompass an extensive array of improved and unimproved germplasm in the Eusorghum. A single locus exists for each of the expressed kafirin-encoding genes, unlike the multigenic α-kafirins. Significant diversity was found for each locus, with the cysteine-rich ß-kafirin having four alleles, including the first natural null mutant reported for this prolamin subfamily. This allele contains a frame shift insertion at +206 resulting in a premature stop codon. SDS-PAGE revealed that lines with this allele do not produce ß-kafirin. An analysis of flour viscosity reveals that these ß-kafirin null lines have a difference in grain quality, with significantly lower viscosity observed over the entire Rapid ViscoAnalyser time course. There was less diversity at the protein level within the cysteine-rich γ-kafirin, with only two alleles in the cultivated sorghums. There were only two alleles for the δ-kafirin locus among the S. bicolor germplasm, with one allele encoding ten extra amino acids, of which five were methionine residues, with an additional methionine resulting from a nucleotide substitution. This longer allele encodes a protein with 19.1% methionine. The Asian species, S. propinquum, had distinct alleles for all three kafirin genes. We found no evidence for selection on the three kafirin genes during sorghum domestication even though the δ-kafirin locus displayed comparatively low genetic variation. This study has identified genetic diversity in all single copy seed storage protein genes, including a null mutant for ß-kafirin in Sorghum.
Assuntos
Alelos , Mutação da Fase de Leitura/genética , Genes de Plantas , Proteínas de Plantas/genética , Prolaminas/genética , Sorghum/genética , Sequência de Bases , Mapeamento Cromossômico , Cisteína/metabolismo , Grão Comestível/química , Grão Comestível/genética , Grão Comestível/metabolismo , Genótipo , Metionina/química , Metionina/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Alinhamento de Sequência , Sorghum/química , Sorghum/metabolismoRESUMO
PURPOSE: Testosterone (T) plays an important role in men's health and its deficiency is linked with poorer health. However, the role of nutritional and lifestyle factors in T regulation and production remains unclear. The objectives are to comprehensively test the cross-sectional associations of nutritional and lifestyle factors with T deficiency and to validate the associations in the NHANES survey. METHODS: We performed weighted multivariable logistic regression analysis to examine the association of 173 nutritional and lifestyle factors with T deficiency (total testosterone ≤ 3.5 ng/mL) in NHANES III as the discovery set (mean age 41). We controlled for multiple comparisons with a false discovery rate (FDR) < 5% and replicated in NHANES 1999-2004 (mean age 44). RESULTS: We identified seven nutritional factors as being inversely associated with T deficiency in NHANES 1999-2004, namely dietary intake of vitamin A, protein, saturated fatty acids, monounsaturated fatty acids, total fats, saturated fatty acid 16:0, and phosphorus. In a multivariable model, only vitamin A intake remained significantly associated with T deficiency (OR 0.97, 95% CI 0.94-0.99). Principal component analysis suggested that the two principal components, (1) dietary fats, protein, and phosphorous and (2) total vitamin A, may be associated with T deficiency. CONCLUSION: Our systematic evaluation provided new insight into the modifiable factors that could play a role in the regulation of T production. This study has the potential to contribute to the current body of literature which seeks to formulate a clinical definition of T deficiency after taking into account nutritional and lifestyle factors.
Assuntos
Ingestão de Alimentos , Estilo de Vida , Estado Nutricional , Testosterona/deficiência , Adulto , Estudos Transversais , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Análise de Componente Principal , Testosterona/sangue , Estados UnidosRESUMO
In view of the Supreme Court decision in Chakrabarty v. Diamond, Commissioner of Patents and Trademarks, it is possible that plant varieties can be protected under three different U.S. statutes: the Plant Variety Protection Act, the Plant Patent Law, and the General Patent Law. The Plant Variety Protection Act protects varieties that are reproduced by seed, whereas the Plant Patent Law protects varieties reproduced asexually. Varieties, irrespective of how they are reproduced, could be patentable under the General Patent Statute. It is not clear whether parts of plants can be protected by grants under the Plant Patent Law or Plant Variety Protection Act and it is possible that they will be best protected under the General Patent Statute and by maintaining them as trade secrets. Only time will show whether the existing statutes are sufficient to provide both guidance and adequate protection or whether changes in the law will be required.
RESUMO
The circadian oscillator of the cyanobacterium Synechococcus elongatus, like those in eukaryotes, is entrained by environmental cues. Inactivation of the gene cikA (circadian input kinase) shortens the circadian period of gene expression rhythms in S. elongatus by approximately 2 hours, changes the phasing of a subset of rhythms, and nearly abolishes resetting of phase by a pulse of darkness. The CikA protein sequence reveals that it is a divergent bacteriophytochrome with characteristic histidine protein kinase motifs and a cryptic response regulator motif. CikA is likely a key component of a pathway that provides environmental input to the circadian oscillator in S. elongatus.
Assuntos
Proteínas de Bactérias , Relógios Biológicos , Ritmo Circadiano , Cianobactérias/fisiologia , Proteínas Quinases/genética , Alelos , Motivos de Aminoácidos , Sequência de Aminoácidos , Relógios Biológicos/genética , Relógios Biológicos/fisiologia , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologia , Cianobactérias/genética , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Genes Reporter , Medições Luminescentes , Dados de Sequência Molecular , Mutação , Fenótipo , Proteínas Quinases/química , Proteínas Quinases/fisiologia , Alinhamento de SequênciaRESUMO
We provide quantitative anatomical data on the muscle-tendon architecture and geometry of the pelvic limb of an elite sprint athlete, the racing greyhound. Specifically, muscle masses, muscle lengths, fascicle lengths, pennation angles and muscle moment arms were measured. Maximum isometric force and power of muscles, the maximum muscle torque at joints and tendon stress and strain were estimated. We compare data with that published for a generalized breed of canid, and other cursorial mammals such as the horse and hare. The pelvic limb of the racing greyhound had a relatively large volume of hip extensor muscle, which is likely to be required for power production. Per unit body mass, some pelvic limb muscles were relatively larger than those in less specialized canines, and many hip extensor muscles had longer fascicle lengths. It was estimated that substantial extensor moments could be created about the tarsus and hip of the greyhound allowing high power output and potential for rapid acceleration. The racing greyhound hence possesses substantial specializations for enhanced sprint performance.
Assuntos
Cães/anatomia & histologia , Cães/fisiologia , Marcha , Membro Posterior , Articulações/anatomia & histologia , Músculo Esquelético/anatomia & histologia , Adaptação Fisiológica , Animais , Fenômenos Biomecânicos , Contração Isométrica/fisiologia , Articulações/fisiologia , Músculo Esquelético/fisiologia , Pelve , Amplitude de Movimento Articular , Tendões/anatomia & histologia , Tendões/fisiologiaRESUMO
We provide quantitative muscle-tendon architecture and geometry data for the racing greyhound thoracic limb. Muscle mass, belly length, fascicle lengths, pennation angles and moment arms were measured, as were tendon masses and lengths. Maximum isometric force and maximum power were estimated for muscles, and maximum stress and strain were estimated for tendons. Results are compared with other fast quadrupedal runners, and to previously published data in mixed-breed dogs. The implications of the functional adaptations of the greyhound thoracic limb for sprinting performance are discussed. The thoracic limb was found to benefit from a similar proportion of locomotor muscle mass to the pelvic limb, suggesting that it may be used to some extent in propulsion, or alternatively that stabilisation is very important in this animal. Extrinsic muscles, especially latissimus dorsi and pectoralis profundus, were predicted to be powerful and important for generating net positive work during accelerations. Proximal biarticular muscles show specialisation toward preventing collapse of the shoulder and elbow joints to enable strut-like limb function, or some form of dynamic control. Distal muscles did not appear specialised for elastic energy storage, a functional difference to pelvic limb muscles, and the equivalents in horse thoracic limbs. The greyhound thoracic limb appears to possess substantial differences from both that of more 'sub-maximal specialist' quadrupeds, and from the greyhound pelvic limb.
Assuntos
Cães/anatomia & histologia , Membro Anterior , Marcha , Músculo Esquelético/anatomia & histologia , Adaptação Fisiológica , Animais , Fenômenos Biomecânicos , Cães/fisiologia , Contração Isométrica , Articulações/anatomia & histologia , Articulações/fisiologia , Músculo Esquelético/fisiologia , Amplitude de Movimento Articular , Tendões/anatomia & histologia , Tendões/fisiologiaRESUMO
Asialo von Willebrand factor (AS-vWf) binds to and aggregates normal human platelets in the absence of ristocetin. Maximal specific binding of AS-vWf is 1-2 micrograms vWf protein/10(8) platelets. Despite the specificity of the binding, only 60% of the bound AS-vWf can be dissociated after equilibrium has been reached. We investigated the site of binding and the mechanism of aggregation of platelets by AS-vWf by (a) pre-incubating platelets with either of two monoclonal antibodies, one against glycoprotein Ib (GPIb) or a second against the glycoprotein IIb/IIIa complex (GPIIb/IIIa), and (b) varying the concentration of fibrinogen in the medium. The results of our studies indicate that AS-vWf binds initially to GPIb. This binding then results in the exposure of receptors for AS-vWf on GPIIb/IIIa. In the presence of plasma fibrinogen, both AS-vWf and fibrinogen bind to GPIIb/IIIa. In the presence of plasma fibrinogen, 50% more AS-vWf binds to the platelet, and this additional AS-vWf binds almost exclusively to GPIIb/IIIa. Despite this enhanced binding of AS-vWf in the absence of fibrinogen, platelet aggregation is much less than that which occurs in the presence of plasma fibrinogen. Comparative studies of AS-vWf binding to normal platelets and the platelets of patients with Glanzmann's thrombasthenia reveal decreased binding to the thrombasthenic platelets and a marked decrease in the extent of platelet aggregation. These studies indicate that AS-vWf binding to, and ensuing aggregation of, platelets is different from that observed with intact vWf protein when platelets are stimulated with either ristocetin or thrombin. The AS-vWf binds to GPIb which, in turn, makes additional AS-vWf receptors available on GPIIb/IIIa. If plasma fibrinogen is present, it competes with the AS-vWf for binding to GPIIb/IIIa and causes aggregation of platelets. In the presence of plasma fibrinogen, more of the AS-vWf binds to GPIIb/IIIa, but this AS-vWf is much less effective than fibrinogen in supporting platelet aggregation.
Assuntos
Assialoglicoproteínas , Fatores de Coagulação Sanguínea/metabolismo , Plaquetas/fisiologia , Glicoproteínas/fisiologia , Proteínas de Membrana/fisiologia , Fator de von Willebrand/metabolismo , Anticorpos Monoclonais , Humanos , Agregação Plaquetária , Glicoproteínas da Membrana de Plaquetas , Receptores de Superfície Celular/fisiologia , Fator de von Willebrand/análogos & derivadosRESUMO
Arg-Gly-Asp (RGD)- and fibrinogen gamma-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa). GP IIb-IIIa, vWF, and Fn are essential for normal platelet adherence to subendothelium. We added peptides to normal citrated whole blood before perfusion over human umbilical artery subendothelium and evaluated platelet adherence morphometrically at high (2,600 s-1) and low (800 s-1) wall shear rates. We also examined the effects of the peptides on platelet adhesion to collagen in a static system. At the high wall shear rate, RGDS and GQQHHLGGAKQAGDV caused dose-dependent reduction in the surface coverage with spread and adherent platelets. Amino acid transposition and conservative substitutions of RGD peptides and the AGDV peptide significantly inhibited platelet adherence at 2,600 s-1. By contrast, the modified RGD peptides and AGDV do not affect adhesive protein binding to platelets. None of the native or modified RGD- or fibrinogen gamma-chain peptides significantly inhibited either platelet adherence to subendothelium at 800 s-1 or platelet adhesion to collagen. Our findings demonstrate that peptides that interfere with adhesive protein binding to GP IIb-IIIa inhibit platelet adherence to vascular subendothelium with flowing blood only at high wall shear rates. Platelet adherence to subendothelium at high wall shear rates appears to be mediated by different recognition specificities from those required for fluid-phase adhesive protein binding or static platelet adhesion.
Assuntos
Endotélio Vascular/metabolismo , Fibrinogênio/farmacologia , Oligopeptídeos/farmacologia , Adesividade Plaquetária/efeitos dos fármacos , Sequência de Aminoácidos , Colágeno/metabolismo , Endotélio Vascular/fisiologia , Humanos , Cinética , Dados de Sequência Molecular , Ligação Proteica , Relação Estrutura-Atividade , Trombina/farmacologia , Artérias Umbilicais , Fator de von Willebrand/metabolismoRESUMO
We have investigated and characterized the abnormalities in four unrelated patients with von Willebrand's disease (vWd) who have (a) enhanced ristocetin-induced platelet aggregation (RIPA) at low ristocetin concentrations, (b) absence of the largest plasma von Willebrand factor (vWf) multimers, and (c) thrombocytopenia. The platelet-rich plasma of these patients aggregates spontaneously without the addition of any agonists. When isolated normal platelets are resuspended in patient plasma spontaneous aggregation occurs; however, the patients' plasmas did not induce platelet aggregation of normal washed formalinized platelets. When the patients' platelets are suspended in normal plasma, spontaneous aggregation is not observed. The spontaneous platelet aggregation (SPA) is associated with dense granule secretion as measured by ATP release and alpha granule release as measured by beta-thromboglobulin and platelet factor 4 release. The SPA is totally inhibited by 5 mM EDTA, prostaglandin I2, and dibutryl cyclic AMP, while it is only partially inhibited by 1 mM EDTA, acetylsalicylic acid, or apyrase. A monoclonal antibody directed against glycoprotein Ib (GPIb) and/or a monoclonal antibody against the glycoprotein IIb/IIIa (GPIIb/IIIa) complex totally inhibits the SPA. The vWf was isolated from the plasma of one of these patients. The purified vWf induced platelet aggregation of normal platelets resuspended in either normal or severe vWd plasma, but the vWf did not induce platelet aggregation of normal platelets resuspended in afibrinognemic plasma. Sialic acid and galactose quantification of the patient's vWf revealed approximately a 50% reduction compared with normal vWf. These studies indicate that a form of vWd exists, which is characterized by SPA that is induced by the abnormal plasma vWf. The SPA is dependent on the presence of plasma fibrinogen, and the availability of the GPIb and the GPIIb/IIIa complex. In this variant form of vWd the abnormal vWf causes enhanced RIPA, SPA, and thrombocytopenia.
Assuntos
Agregação Plaquetária , Doenças de von Willebrand/sangue , Fator de von Willebrand/análise , Antígenos/análise , Fator VIII/análise , Fator VIII/imunologia , Fibrinogênio/metabolismo , Galactose/análise , Glicoproteínas/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas , Ristocetina/farmacologia , Ácidos Siálicos/análise , Trombocitopenia/etiologia , Doenças de von Willebrand/classificação , Doenças de von Willebrand/complicaçõesRESUMO
BACKGROUND: Physician practices that offer ancillary medical services may refer their patients for such services, a process known as self-referral. We wanted to evaluate how utilization and cost of care differ for men diagnosed with prostate cancer in a self-referral practice (SRP) compared to a traditional urologic practice. METHODS: A total of 17 982 men aged 66 years and older diagnosed with localized prostate cancer from 2006 to 2009 were identified from the Texas Cancer Registry. A total of 13 SRPs in the state of Texas were evaluated. We used multilevel logistic regression models that evaluated the odds of receiving a specific type of treatment. RESULTS: Men diagnosed in SRPs were more likely to receive upfront treatment (vs watchful waiting/active surveillance) than men diagnosed by traditional practices (92.7% vs 89%; adjusted odds ratio (AOR) 1.61, 95% confidence interval (CI) 1.30-2.00; P<0.001) and were more likely to be treated with external beam radiation (47.4% vs 34.1%; AOR 1.59, 95% CI 1.37-1.84; P<0.001). This persisted for both favorable and unfavorable risk cancer. Median annual prostate cancer care cost was $2460 (95% CI $1663-$3368) higher for men diagnosed by SRPs. Limitations include data limited to men aged 65 years or older and geographic concentration of SRPs in Texas may not depict nationwide patterns. CONCLUSIONS: Older men diagnosed with prostate cancer in SRPs are more likely to undergo upfront treatment and to receive radiation treatment. This may increase appropriate treatment of unfavorable disease but contribute to overtreatment of favorable disease.
Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia/instrumentação , Idoso , Idoso de 80 Anos ou mais , Custos de Cuidados de Saúde , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Radioterapia/economia , Resultado do Tratamento , UrologistasRESUMO
OBJECTIVES: This study sought to determine whether nitric oxide-mediated vasodilation is abnormal in patients with non-insulin-dependent diabetes mellitus. BACKGROUND: Multiple investigations, both in experimental models and in patients with insulin-dependent diabetes mellitus, demonstrate impaired endothelium-dependent vasodilation. Decreased availability of endothelium-derived nitric oxide may contribute to the high prevalence of vascular disease in diabetes. METHODS: Vascular reactivity was measured in the forearm resistance vessels of 21 patients with non-insulin-dependent diabetes mellitus and 23 matched healthy control subjects. No patient had hypertension or hypercholesterolemia. Each subject was pretreated with aspirin to inhibit endogenous production of vasoactive prostanoids. Methacholine chloride (0.3 to 10 microg/min) was administered through a brachial artery cannula to assess vasodilation to endothelium-derived nitric oxide. Sodium nitroprusside (0.3 to 10 microg/min) was infused to evaluate vasodilation to an exogenous nitric oxide donor. Verapamil (10 to 300 microg/min) was administered to distinguish impaired nitric-oxide-mediated vasodilation from general dysfunction of vascular smooth muscle. Forearm blood flow was determined by venous occlusion plethysmography, and dose-response curves were generated for each agent. To assess the role of vasoconstrictor prostanoids, a subset of eight diabetic subjects were reexamined in the absence of aspirin treatment. RESULTS: Basal forearm blood flow in diabetic and nondiabetic subjects was comparable. The forearm blood flow responses to both methacholine chloride and nitroprusside were significantly attenuated in diabetic compared with nondiabetic subjects (p < 0.005 by analysis of variance for both agents). In contrast, the response to verapamil was not significantly different between the groups (p > 0.50). The forearm blood flow responses to these agents were not significantly affected by cyclooxygenase inhibition. CONCLUSIONS: Nitric oxide-mediated vasodilation is impaired in non-insulin-dependent diabetes mellitus. Vasoconstrictor prostanoids do not contribute significantly to vascular dysfunction. The attenuated response to exogenous as well as endogenous nitric oxide donors suggests that the abnormality is due to increased inactivation of nitric oxide or to decreased reactivity of the vascular smooth muscle to nitric oxide.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Antebraço/irrigação sanguínea , Óxido Nítrico/fisiologia , Adulto , Análise de Variância , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Constrição Patológica/fisiopatologia , Feminino , Humanos , Masculino , Cloreto de Metacolina/farmacologia , Nitroprussiato/farmacologia , Parassimpatomiméticos/farmacologia , Vasodilatadores/farmacologia , Verapamil/farmacologiaRESUMO
PURPOSE: Several mechanisms have been proposed to explain the prolonged bleeding times and clinical bleeding in chronic renal failure. Recent evidence has implicated an abnormality in the structure or function of the von Willebrand factor or in its interaction with uremic platelets. We investigated this factor in 11 patients with chronic renal failure. PATIENTS AND METHODS: Blood samples for cell counts, chemistries, and coagulation studies were obtained from 11 patients with chronic renal failure and prolonged bleeding times. Concentrations of von Willebrand factor antigen and ristocetin cofactor activity were determined in plasma and platelets. Multimeric analysis of von Willebrand factor in plasma and platelets was conducted. In eight cases, the platelets of uremic patients were purified, and the thrombin- and ristocetin-induced binding of normal von Willebrand factor to these platelets was examined. RESULTS: The mean plasma von Willebrand factor antigen and activity (ristocetin cofactor assay) were elevated 2.77 mu/ml and 1.88 mu/ml, respectively (normal, 1.01 mu/ml and 1.07 mu/ml, respectively). The ratio of activity to antigen in uremic plasma was 0.67 (normal, 1.05). The mean platelet von Willebrand factor antigen and activity in the uremic patients was decreased (0.26 and 0.50 mu/10(9) platelets, respectively) compared with normal patients (0.46 and 0.93 mu/10(9) platelets, respectively). The oligomeric structure of the uremic plasma von Willebrand factor lacked the largest multimers. Collection of the blood for analysis in several protease inhibitors and/or EDTA did not change the multimeric structure. The von Willebrand factor multimeric structure of platelets from uremic patients was normal. The ristocetin-induced platelet aggregation of the uremic platelet-rich plasma was decreased compared with normal plasma samples. Thrombin and ristocetin-induced binding of normal von Willebrand factor to uremic patients' platelets was indistinguishable from the binding to normal platelets. CONCLUSION: These data suggest that the uremic platelet-binding sites for von Willebrand factor are intact and that the defect in ristocetin-induced platelet aggregation is most likely plasmatic in nature. At least one plasmatic defect was the observed reduction or absence of the largest plasma von Willebrand factor multimer in uremic patients. The platelet von Willebrand content was significantly decreased. These defects may play a role in the prolonged bleeding time and the clinical bleeding observed in patients with uremia.
Assuntos
Plaquetas/metabolismo , Uremia/sangue , Fator de von Willebrand/análise , Tempo de Sangramento , Cromatografia em Agarose , Humanos , Falência Renal Crônica/sangue , Peso Molecular , Agregação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas , Ligação Proteica/efeitos dos fármacos , Ristocetina/farmacologia , Fator de von Willebrand/metabolismoRESUMO
Inflammatory pseudotumor is a pathologic term used to describe reactive, pseudoneoplastic phenomena, which reportedly occur in many parts of the body. Clinicopathologic and immunohistochemical findings in six cases of inflammatory pseudotumor of the major salivary glands are described. All six lesions involved the parotid gland. There were three men and three women affected, with a median age of 72.5 years. All patients presented with a swelling of several months' duration in the parotid region. Five patients were alive and free of tumor at an average of 3.2 years after surgical removal, and one patient was lost to follow-up. The lesions were firm, discrete nodules, grossly described as homogenous yellow-gray tissue. Histologically, all lesions contained a diversified admixture of four histological elements: (a) myofibroblasts, (b) histiocytes, (c) plasma cells, and (d) lymphocytes. Results of immunohistochemical studies showed a biphasic spindle cell population of myofibroblasts and histiocytes with variable staining characteristics for KP-1(CD-3), smooth muscle actin, muscle-specific actin, and vimentin. These findings are in agreement with the concept that inflammatory pseudotumor is a fibroinflammatory lesion with an abundant component of myofibroblastic/fibrohistiocytic elements.
Assuntos
Granuloma de Células Plasmáticas/patologia , Doenças das Glândulas Salivares/patologia , Actinas/análise , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Glândulas Salivares/química , Glândulas Salivares/patologia , Vimentina/análiseRESUMO
We present 19 cases of a previously undescribed myxoid tumor of the anterior tongue. These lesions occurred in nine women and 10 men aged 9 to 78 years (median, 32 years). Most tumors were seen as slow growing, painless nodules in the anterior dorsal tongue. The duration of growth ranged from a few months to 10 years. All tumors were treated by surgical excision, and two recurred. Microscopically, they exhibited a lobular proliferation of ovoid and fusiform cells, which often had multilobated nuclei and occasional foci of atypia, in a chondromyxoid background. Some tumors entrapped muscle or nerve fibers and had a tendency for blunt infiltration of adjacent tissue. The cells were diffusely and intensely immunoreactive for glial fibrillary acidic protein (GFAP) and cytokeratin but were decorated less frequently with antibodies for smooth muscle actin and S-100 protein. Reactivity for epithelial membrane antigen and desmin was not found. We believe these tumors fail to meet established clinicopathologic criteria for any existing myxoid neoplasms of the tongue, including nerve sheath myxoma, myoepithelioma, benign mixed tumor, ossifying fibromyxoid tumor of soft parts, extraskeletal myxoid chondrosarcoma, and glial and chondroid choristomas or heterotopias. Although the histogenesis of this neoplasm is unclear, we suspect that a cell of undifferentiated ectomesenchyme is the progenitor and suggest the descriptive term ectomesenchymal chondromyxoid tumor (ECT) of the anterior tongue be adopted.
Assuntos
Neoplasias de Tecido Conjuntivo/patologia , Neoplasias da Língua/patologia , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo/ultraestrutura , Neoplasias da Língua/ultraestruturaRESUMO
Unstimulated human platelets from normal volunteers adhere to sulfatides (galactosylceramide-I3-sulfate) as single cells but do not adhere appreciably to other lipids including gangliosides, neutral glycolipids, phospholipids or cholesterol-3-SO4. Platelet adhesion to sulfatide is saturable and dose-dependent, reaches maximal levels in 90 to 120 min, and is not divalent cation-dependent. Because sulfatides bind von Willebrand factor (vWf) with specificity and high affinity and platelet adhesion to structurally related sulfated glycolipids is approximately proportionate to their ability to bind vWf, we examined whether vWf mediates platelet adhesion to sulfatides. Platelets from a patient with severe Type I von Willebrand's disease adhere poorly to sulfatides. However, adhesion to levels seen with normal platelets is restored by the addition of vWf. Adhesion of normal platelets can be partially inhibited by a monospecific antibody to vWf. Normal platelet adhesion to sulfatides, however, is not increased following preincubation with vWf. Both vWf binding and platelet adhesion to sulfatides can be inhibited by the sulfated polysaccharide dextran sulfate at low concentration, fucoidan at high concentrations, but not by heparin, fibrinogen, fibronectin, or the synthetic peptides Gly-Arg-Gly-Asp-Ser-Pro or Gly-Arg-Gly-Glu-Ser-Pro. Thus, adhesion to sulfatides appears to be of two types; vWf dependent (50-75%) and vWf independent (25-50%).
Assuntos
Hemostasia/fisiologia , Adesividade Plaquetária/fisiologia , Sulfoglicoesfingolipídeos/sangue , Fator de von Willebrand/fisiologia , Sequência de Aminoácidos , Glicolipídeos/sangue , Humanos , Radioisótopos de Índio , Radioisótopos do Iodo , Metabolismo dos Lipídeos , Dados de Sequência Molecular , PlásticosRESUMO
von Willebrand factor (vWF) circulates in the blood in two distinct compartments. One, plasma vWF, is synthesized and released from endothelial cells; the second, synthesized by megakaryocytes, circulates in platelets primarily stored in the alpha granules. Recent experimental and clinical studies of von Willebrand's disease (vWD) indicate that platelet vWF plays an important role in the bleeding time determination and the degree of clinical bleeding in vWD. Platelet vWF is released from the platelet alpha granules by various agonists and then rebinds to the glycoprotein IIb/IIIa complex. Fibrinogen or monoclonal antibodies against this complex inhibit 60 to 70% of the expression of platelet vWF. Aspirin inhibits 80% of the adenosine diphosphate-induced platelet vWF surface expression, and the platelet vWF surface expression that is not inhibited by aspirin can be almost totally inhibited by disruption of the platelet cytoskeleton. Platelet vWF may, in part, be expressed in the open canalicular system prebound to a receptor. Transfusion studies have shown that correction of the bleeding time in severe vWD requires both plasma and platelet vWF. On the basis of numerous studies, we hypothesize that platelet vWF plays an important role in platelet interaction with the subendothelial surfaces under conditions of high shear stress. After platelet contact, platelet vWF is released, binds to the glycoprotein IIb/IIIa complex, and forms a bridge between the subendothelial surface and the platelet, which initiates and supports platelet spreading. Platelet vWF also acts as an intercellular bridge between platelets and thereby promotes platelet aggregation. This process is important not only in the initial steps of hemostasis but also in the process of thrombosis.