Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Environ Manage ; 183(Pt 3): 601-612, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27633144

RESUMO

Acid mine drainage (AMD) impacted waters are a worldwide concern for the mining industry and countries dealing with this issue; both active and passive technologies are employed for the treatment of such waters. Mussel shell bioreactors (MSB) represent a passive technology that utilizes waste from the shellfish industry as a novel substrate. The aim of this study is to provide insight into the biogeochemical dynamics of a novel full scale MSB for AMD treatment. A combination of water quality data, targeted geochemical extractions, and metagenomic analyses were used to evaluate MSB performance. The MSB raised the effluent pH from 3.4 to 8.3 while removing up to ∼99% of the dissolved Al, and Fe and >90% Ni, Tl, and Zn. A geochemical gradient was observed progressing from oxidized to reduced conditions with depth. The redox conditions helped define the microbial consortium that consists of a specialized niche of organisms that influence elemental cycling (i.e. complex Fe and S cycling). MSB technology represents an economic and effective means of full scale, passive AMD treatment that is an attractive alternative for developing economies due to its low cost and ease of implementation.


Assuntos
Exoesqueleto/microbiologia , Bactérias/metabolismo , Reatores Biológicos/microbiologia , Metais/metabolismo , Enxofre/metabolismo , Poluentes Químicos da Água/metabolismo , Ácidos/metabolismo , Animais , Bactérias/genética , Bivalves , Concentração de Íons de Hidrogênio , Metais/análise , Consórcios Microbianos , Mineração , Análise de Componente Principal , RNA Ribossômico 16S/genética , Enxofre/análise , Poluentes Químicos da Água/análise
2.
Thorac Cardiovasc Surg ; 51(4): 190-5, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14502455

RESUMO

OBJECTIVES: The function of the anterior mitral basal "stay" chords (SC) is not yet known. Collagen fiber orientation of the anterior mitral leaflet (AML) suggests that local stress is directed from papillary muscles (PM) over SC and AML to fibrous trigones (FT), maintaining the aortomitral angle (AMA). It has been shown that narrowing of AMA increases risk of systolic anterior movement (SAM). METHODS: Sonomicrometry crystals were implanted in six sheep at the left ventricular (LV) apex, PM tips (M1, M2), FT (T1, T2), posterior mitral annulus (PMA), and base of aortic right coronary sinus (RCS). The retracting force of ascending aorta was measured. RESULTS: Transection of SC resulted in an increase of distance M1-T1 and M2-T2. Consequently, the AMA narrowed at end systole by -3.26+/-0.85 degrees (p<0.05) and at end diastole by -4.16+/-1.28 degrees (p<0.05). A force of 1.8+/-0.2 N was needed to pull the recoiling ascending aorta back to its original position. CONCLUSIONS: The elastic recoil of ascending aorta is balanced by SC, which connect PM to FT and constitute the center of the LV base. Transection of SC narrows AMA and increases the risk of SAM.


Assuntos
Aorta/fisiologia , Valva Mitral/fisiologia , Animais , Aorta/anatomia & histologia , Fenômenos Biomecânicos , Hemodinâmica , Valva Mitral/anatomia & histologia , Contração Miocárdica , Músculos Papilares/anatomia & histologia , Músculos Papilares/fisiologia , Ovinos
3.
Teratology ; 64(2): 79-82, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11460258

RESUMO

BACKGROUND: Pregnancy outcome studies conducted through Teratology Information Services (TIS) rely on volunteer subjects. If these subjects tend to have different risk profiles than the population from which they are drawn, the results of TIS studies may have limited generalizability. METHODS: We selected all subjects who enrolled in the California Teratogen Information Service (CTIS) pregnancy outcome study for prenatal exposure to carbamazepine or valproic acid between 1990 and 1997 and who received prenatal care through Kaiser Permanente of Southern California (n = 13). We compared these subjects to Kaiser patients identified through the Maternal Serum Alpha Fetoprotein Program with exposure to carbamazepine or valproic acid but who had not enrolled in the CTIS project. The controls were matched by Kaiser location and pregnancy year using a 2:1 ratio (n = 26). Medical records were reviewed and the prevalence of 14 pregnancy risk factors was compared between the two groups. RESULTS: There were no significant differences between the groups on any one risk factor; however, a notably higher proportion of women who did not enroll in the CTIS study used tobacco or had a positive family history of congenital anomalies. CONCLUSIONS: Although the sample was small, and results may not apply to other exposures in different health care environments, these data provide some evidence that women who enroll in TIS pregnancy outcome studies do not have a substantially different pregnancy risk profile than women who do not. Efforts to address possible selection bias should be incorporated in future TIS study design.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Serviços de Informação sobre Medicamentos/estatística & dados numéricos , Resultado da Gravidez , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Anticonvulsivantes/efeitos adversos , California/epidemiologia , Carbamazepina/efeitos adversos , Feminino , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fatores de Risco , Viés de Seleção , Ácido Valproico/efeitos adversos
4.
J Heart Valve Dis ; 10(6): 728-34; discussion 734-5, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11767178

RESUMO

BACKGROUND AND AIM OF THE STUDY: Aortic valve homografts were treated with 50% ethanol and glycerol followed by freeze-drying (D-Hydro). Comparative results of fresh versus D-Hydro-treated aortic roots implanted for up to nine months in the descending aorta of sheep with induced aortic regurgitation (AR) are reported. METHODS: Six fresh and six D-Hydro valves were implanted in 12 sheep for three, six and nine months, and echocardiography and pressures were taken at surgery and sacrifice. Tissue sections were stained with hematoxylin and eosin, von Kossa, Masson's trichrome, Movat's pentachrome, von Willebrand factor, CD3 (a T-cell marker) and smooth muscle alpha-actin. RESULTS: No grafts had increased gradients after implantation, or at sacrifice. At explantation, fresh homografts showed early pannus formation followed by thrombus, annular dilatation and wall calcification. Leaflets were thickened and progressively retracted. All had severe AR. The appearance of D-Hydro-treated homografts was normal, except for mild leaflet retraction in three, resulting in AR (in two animals the induced AR had healed). Histologically, a T-cell-mediated reaction was evident in the fresh homografts, and collagen distortion was noted. Calcification was present in all fresh specimens and was severe at nine months. D-Hydro roots showed only minor calcification in the six-month samples. Normal collagen, and a complete layer of von Willebrand factor-stained cells were present at three months. At nine months, cell rehabitation extended for two-thirds of the leaflets (alpha-actin +). The inflammatory reaction was very mild, with CD3+-stained cells absent in most samples. CONCLUSION: Aortic valve homografts treated with the D-Hydro freeze-drying method performed better than fresh homografts due to the absence of thrombus and annulus dilatation, limited calcification, and rehabitation of the aortic wall and parts of the leaflet by myofibroblasts, as well as the presence of a complete endothelial layer on the aortic wall and leaflet.


Assuntos
Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/transplante , Preservação de Órgãos/métodos , Animais , Aorta Torácica/patologia , Aorta Torácica/fisiopatologia , Aorta Torácica/cirurgia , Valva Aórtica/patologia , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/patologia , Insuficiência da Valva Aórtica/fisiopatologia , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Feminino , Liofilização/métodos , Masculino , Ovinos , Fatores de Tempo , Transplante Homólogo
5.
J Mol Cell Cardiol ; 32(7): 1327-39, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10860773

RESUMO

The novel glycolipid RC-552 shares common structural features with the natural products lipid A and the previously described cardioprotectant monophosphoryl lipid A. RC-552 administered to dogs as a bolus intravenous dose (35-70 microg/kg) either 24 h or 10 min prior to 60 min of regional myocardial ischemia and 3 h of reperfusion significantly (P<0.05 v control) reduced infarct size (IS) as assessed by triphenyltetrazolium staining from 27.0+/-2.3% of the area-at-risk (AAR) to 13.3+/-2.2% and 15.0+/-3.0%, respectively. Administration of the non-specific inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (30 mg/kg, subcutaneously) 1 h prior to ischemia blocked the ability of RC-552 (35 microg/kg, 24 h pretreatment) to reduce infarct size. Intravenous pretreatment with RC-552 (35 microg/kg) either 24 h or 10 min prior to five 5 min repetitive cycles of ischemia and reperfusion significantly improved regional myocardial segment shortening (percentage of control) at all time points during 2 h of reperfusion in dogs. These effects of RC-552 in either cardiac injury model occurred independent of differences in AAR, transmural blood flow during ischemia or hemodynamics throughout the experiment. In contrast with monophosphoryl lipid A (MLA), which has also been reported to be cardioprotective at similar doses in dogs, RC-552 was approximately 100 times less prone to cause fever in the USP rabbit pyrogen test. Likewise, RC-552 did not induce secretion of the proinflammatory cytokines TNF, IL-6 or IL-8 from THP-1 cells or alter the expression of adhesion molecules on human neutrophils at concentrations up to 10 microg/ml. MLA was active in these systems at concentrations in the range 0.1-1.0 microg/ml. In conclusion, RC-552 reduces myocardial infarct size and stunning in dogs in the absence of residual immunomodulatory activity.


Assuntos
Glicolipídeos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Miocárdio Atordoado/tratamento farmacológico , Animais , Anticorpos Monoclonais , Velocidade do Fluxo Sanguíneo , Cães , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Glicolipídeos/química , Hemodinâmica , Humanos , Molécula 1 de Adesão Intercelular/biossíntese , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Selectina L/sangue , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Lipídeo A/análogos & derivados , Lipídeo A/química , Lipídeo A/farmacologia , Lipopolissacarídeos/farmacologia , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Coelhos , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/biossíntese
6.
Braz J Med Biol Res ; 33(4): 369-78, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10775301

RESUMO

Although gap junction channels are still widely viewed as large, non-specific pores connecting cells, the diversity in the connexin family has led more attention to be focused on their permeability characteristics. We summarize here the current status of these investigations, both published and on-going, that reveal both charge and size selectivity between gap junction channels composed of different connexins. In particular, this review will focus on quantitative approaches that monitor the expression level of the connexins, so that it is clear that differences that are seen can be attributed to channel properties. The degree of selectivity that is observed is modest compared to other channels, but is likely to be significant for biological molecules that are labile within the cell. Of particular relevance to the in vivo function of gap junctions, recent studies are summarized that demonstrate that the connexin phenotype can control the nature of the endogenous traffic between cells, with consequent effects on biological effects of gap junctions such as tumor suppression.


Assuntos
Permeabilidade da Membrana Celular/fisiologia , Conexinas/fisiologia , Junções Comunicantes/fisiologia , Canais Iônicos/fisiologia , Animais , Comunicação Celular , Tamanho Celular , Células HeLa , Humanos , Potenciais da Membrana/fisiologia
7.
Ophthalmology ; 106(10): 2023-6, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10519602

RESUMO

OBJECTIVE: To study the effectiveness of neodymium:YAG (Nd:YAG) laser transconjunctival revision of late-failing filtering blebs. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Thirty consecutive patients from a glaucoma referral practice at the Ohio State University Department of Ophthalmology. INTERVENTION: Transconjunctival Nd:YAG laser revision of blebs diagnosed as failing secondary to episcleral fibrosis. MAIN OUTCOME MEASURE: Reduction in intraocular pressure (IOP) and survival of bleb. RESULTS: Reduction in IOP was attained in 24 (80%) of 30 patients with a mean prelaser IOP of 21.21 mmHg and a mean 1-week postlaser IOP of 13.97 mmHg (P < 0.0001). These results were maintained at the 1-, 3-, and 12-month follow-up visits with mean IOPs of 16.31 mmHg (P = 0.0008), 14.81 mmHg (P < 0.0001), and 15.25 mmHg (P = 0.0003), respectively. Two-year data were available on a small number of patients (4) with a mean of 15.25 mmHg (P = 0.0085). Mean time interval between trabeculectomy and laser revision was 31 months. CONCLUSION: Late-failing filtering blebs are often amenable to Nd:YAG transconjunctival revision.


Assuntos
Túnica Conjuntiva/cirurgia , Glaucoma/cirurgia , Terapia a Laser , Trabeculectomia , Idoso , Idoso de 80 Anos ou mais , Túnica Conjuntiva/diagnóstico por imagem , Feminino , Fibrose/complicações , Glaucoma/etiologia , Glaucoma/patologia , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Esclera/patologia , Esclerostomia , Falha de Tratamento , Ultrassonografia
8.
Lasers Surg Med ; 25(4): 348-62, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10534751

RESUMO

BACKGROUND AND OBJECTIVES: Despite disparate treatment parameters, similar success in laser trabeculoplasty (LT) is attained using the argon (514.5 nm) and diode (810 nm) laser. However, the mechanism of this success remains unresolved. To further understand LT, this study characterizes the optical properties of trabecular meshwork (TM). STUDY DESIGN/MATERIALS AND METHODS: Reflectance was measured from 10 TM samples over wavelengths of 400-820 nm, using an integrating sphere/spectrophotometer. Corrections were made for reflections at boundaries of refractive index mismatch. Kubelka-Munk coefficients were calculated and converted to linear transport coefficients. RESULTS: Scattering greatly dominated absorption. The scattering and absorption coefficients were, respectively, 141.20 +/- 15.80 cm(-1) and 4.89 +/- 1.95 cm(-1) at 514.5 nm, and 94.44 +/- 15.03 cm(-1) and 0.0874 +/- 0.111 cm(-1) at 810 nm (estimated anisotropy of 0.90). The corresponding penetration depths (1/e) were 69 microm (514.5 nm) and 106 microm (810 nm). CONCLUSION: The absorption coefficient of 514 nm energy is two orders of magnitude greater than 810 nm energy, while scattering coefficients are much closer. The fluence used at 514.5 nm is higher at the surface than that at 810 nm, but falls below it deep within the TM due to the differential absorption. Therefore, similar initial therapeutic effects are obtained with 810 nm using less total absorbed energy. Thermal damage resultant from excess energy deposited at 514.5 nm may be related to the lack of success in repeat argon LT, pointing out the need for studies of repeat diode LT.


Assuntos
Terapia a Laser/métodos , Óptica e Fotônica , Malha Trabecular/química , Trabeculectomia/métodos , Visão Ocular , Anisotropia , Argônio/química , Humanos , Técnicas In Vitro , Modelos Biológicos , Sensibilidade e Especificidade , Espectrofotometria , Visão Ocular/fisiologia , Visão Ocular/efeitos da radiação
9.
Dig Dis Sci ; 43(1): 170-7, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9508521

RESUMO

Hepatic bile synthesis is altered during experimental gallstone formation. In response to cholesterol, there is a hydrophobic shift in hepatic bile acid synthesis and hypersecretion of phospholipids. These changes decrease the vesicular capacity for cholesterol and favor crystallization. The mechanism for these changes in hepatic bile formation is unknown. Calmodulin (CaM), a Ca2+ receptor protein involved in cellular secretion, regulates gallbladder transport and may play an important role in alterations of hepatic bile formation during cholelithiasis. We hypothesized that biliary CaM activity is altered during gallstone formation and may be associated with changes in bile acid and phospholipid synthesis. Prairie dogs were fed either control (N = 22) or 1.2% cholesterol-enriched (N = 26) diets for one to six weeks. Cholecystectomy was performed; the common bile duct was cannulated, and hourly bile samples were collected. CaM was measured in bile and gallbladder tissues by radioimmunoassay. Bile samples were analyzed for cholesterol, phospholipids, total bile acids, total protein, calcium, and individual bile acid composition. Compared to controls, gallstone animals had elevated hepatic bile levels of CaM, phospholipids, and cholesterol. Hydrophobic bile acid synthesis was also stimulated, with increased levels of taurochenodeoxycholic acid (TCDCA) and decreased taurocholic acid (TCA). Gallbladder bile demonstrated similar changes. Although gallbladder bile CaM levels were increased, tissue levels were unchanged, suggesting that increased CaM concentration is a hepatic phenomenon. Hepatic bile CaM activity correlated linearly with TCDCA concentration (r = 0.64, P < 0.004) and phospholipid hypersecretion (r = 0.53, P < 0.03). The relationship between biliary CaM and increased concentrations of TCDCA and phospholipids suggests a role for CaM in alterations of hepatocyte secretion that may promote gallstone formation.


Assuntos
Bile/química , Calmodulina/análise , Colelitíase/metabolismo , Animais , Colesterol/análise , Vesícula Biliar/metabolismo , Fígado/metabolismo , Masculino , Fosfolipídeos/análise , Sciuridae , Ácido Taurocólico/análise
10.
Am J Ophthalmol ; 125(2): 270-2, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9467466

RESUMO

PURPOSE: To report ocular injuries associated with the use of bungee cords. METHOD: Four patients with bungee cord-associated ocular trauma are presented. RESULTS: Four eyes of four patients demonstrated severe contusion injuries associated with bungee cord trauma. Ocular injuries in the four eyes included a variable combination of corneal abrasion, hyphema, iridodialysis, anterior chamber angle recession, secondary glaucoma, lens subluxation, vitreous hemorrhage, and retinal detachment. Three of the four eyes required ophthalmic surgery. All eyes had anterior chamber angle recession and required continuing ophthalmic care. CONCLUSION: Bungee cords may be associated with severe ocular injury and should be used with caution.


Assuntos
Acidentes Domésticos , Traumatismos Oculares/etiologia , Borracha , Ferimentos não Penetrantes/etiologia , Adulto , Segmento Anterior do Olho/lesões , Doenças da Córnea/etiologia , Traumatismos Oculares/patologia , Feminino , Glaucoma/etiologia , Humanos , Doenças da Íris/etiologia , Subluxação do Cristalino/etiologia , Cristalino/lesões , Masculino , Pessoa de Meia-Idade , Retina/lesões , Descolamento Retiniano/etiologia , Corpo Vítreo/lesões , Hemorragia Vítrea/etiologia , Ferimentos não Penetrantes/patologia
11.
Vision Res ; 37(16): 2295-301, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9578910

RESUMO

Achromatic losses in glaucoma would be expected to be greater than, or equal to, red-green chromatic losses if the following assumptions are made: (1) the function of the remaining axons is either unchanged or non-selectively reduced; (2) red-green chromatic information is signaled by the midget ganglion cell system; and (3) the function of the magnocellular system is reduced at least as much as that of the midget ganglion cells. This prediction was tested by measuring red-green (along with blue-yellow) mixture thresholds for 1 deg, 0.2 sec test spots presented on a color monitor on a white background of 50 cd/m2. Ellipses were fitted to plots of green contrast as a function of red contrast (or yellow as a function of blue), and major and minor axes of these ellipses were taken as measures of chromatic and achromatic thresholds, respectively. The study population consisted of 29 eyes in 29 patients with early glaucoma; control data were derived from a data bank of 83 normal eyes. Red-green losses were significantly (P < 0.05) greater than achromatic losses in 6 out of the 11 eyes which showed significant losses of either chromatic or achromatic sensitivity (or both). It is concluded that, for these eyes, at least one of the above three assumptions is incorrect.


Assuntos
Defeitos da Visão Cromática/fisiopatologia , Glaucoma/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Limiar Sensorial/fisiologia , Transtornos da Visão/fisiopatologia
12.
J Mol Cell Cardiol ; 29(6): 1567-76, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9220342

RESUMO

Pretreatment with monophosphoryl lipid A (MLA) can pharmacologically mimic the second window of ischemic preconditioning (SWOP) to protect the heart from prolonged ischemia and reperfusion injury. Based on the delayed time course for development of MLA associated cardioprotection, this study was designed to test if MLA's cardioprotective effect is mediated by signalling through production of inducible nitric oxide synthase (iNOS), a proposed effector of SWOP. Rabbits were assigned to one of four groups: (1) vehicle control; (2) MLA: (3) vehicle+aminoguanidine (AMG) control; or (4) MLA+AMG. Monophosphoryl lipid A (35 micrograms/kg) or vehicle was given intravenously 24 h before ischemia. The selective iNOS inhibitor AMG (300 mg/ kg) was injected subcutaneously 1 h before ischemia. All rabbits experienced 30 min coronary artery occlusion followed by 3 h of reperfusion. Infarct size was measured by triphenyltetrazolium chloride (TTC) staining. followed by 3 h of reperfusion. Infarct size was measured by triphenyltetrazolium chloride (TTC) staining. Myeloperoxidase activity, an index of neutrophil infiltration, was also quantified in heart tissue collected from the post-ischemic viable border zone surrounding the infarct area. MLA pretreatment significantly reduced infarct size and neutrophil infiltration in rabbit hearts compared to control (P < 0.05). Inhibition of iNOS activity by AMG abolished the infarct size reductive effect of MLA. Aminoguanidine also blocked the ability of MLA to significantly reduce neutrophil infiltration. Although measurement of iNOS activity did not show induction of the enzyme in normal myocardial tissue 24 h after MLA pretreatment, an increase in iNOS activity in ischemic tissue relative to non-ischemic tissue was found after either 15 or 30 min of coronary occlusion in MLA treated rabbits. These results suggest that MLA pretreatment may enhance iNOS enzyme activity by MLA during ischemia which may be responsible for the observed cardioprotection.


Assuntos
Precondicionamento Isquêmico Miocárdico , Lipídeo A/análogos & derivados , Miocárdio/enzimologia , Óxido Nítrico Sintase/fisiologia , Adjuvantes Imunológicos/farmacologia , Animais , Coração/efeitos dos fármacos , Hemodinâmica , Lipídeo A/farmacologia , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/patologia , Óxido Nítrico Sintase/efeitos dos fármacos , Peroxidase/metabolismo , Coelhos
13.
J Glaucoma ; 5(6): 406-9, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8946297

RESUMO

PURPOSE: We report the first case of retinal myelin loss associated with uncontrolled primary open angle glaucoma (POAG). METHODS: The clinical features, visual fields, and serial disc photos documenting the changes are described. The literature regarding this phenomenon in other forms of optic neuropathy and the specific implications in glaucoma patients are discussed. RESULTS: A 75-year-old black man with POAG had medullated nerve fibers of the retina bilaterally abutting the optic discs inferonasally. Optic disc appearance and visual fields were stable over 6 years. The patient was then lost to follow-up for 2 years and returned with elevated intraocular pressures (IOPs), visual acuity and field loss, progressive optic disc damage, peripapillary atrophy, and disappearance of retinal myelin on the left greater than the right. Retinal myelin loss occurred in areas of nerve fiber layer dropout. CONCLUSIONS: Loss of medullated nerve fibers in the retina occurs secondary to anterograde axonal degeneration as a nonspecific response to any form of optic atrophy. The apparent paucity of glaucoma patients with retinal myelin may be due to late referral rather than any inherent protective effect of retinal myelin against elevated IOP.


Assuntos
Glaucoma de Ângulo Aberto/complicações , Bainha de Mielina/patologia , Fibras Nervosas/patologia , Nervo Óptico/patologia , Fotografação , Retina/patologia , Idoso , Fundo de Olho , Humanos , Pressão Intraocular , Masculino , Acuidade Visual , Campos Visuais
14.
Proc Natl Acad Sci U S A ; 92(25): 11456-60, 1995 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-8524782

RESUMO

Integration of human immunodeficiency virus (HIV) DNA into the human genome requires the virus-encoded integrase (IN) protein, and therefore the IN protein is a suitable target for antiviral strategies. To find a potent HIV IN inhibitor, we screened a "synthetic peptide combinatorial library." We identified a hexapeptide with the sequence HCKFWW that inhibits IN-mediated 3'-processing and integration with an IC50 of 2 microM. The peptide is active on IN proteins from other retroviruses such as HIV-2, feline immunodeficiency virus, and Moloney murine leukemia virus, supporting the notion that a conserved region of IN is targeted. The hexapeptide was also tested in the disintegration reaction. This phosphoryl-transfer reaction can be carried out by the catalytic core of IN alone, and the peptide HCKFWW was found to inhibit this reaction, suggesting that the hexapeptide acts at or near the catalytic site of IN. Identification of an IN hexapeptide inhibitor provides proof of concept for the approach, and, moreover, this peptide may be useful for structure-function analysis of IN.


Assuntos
DNA Nucleotidiltransferases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , HIV-1/enzimologia , Oligopeptídeos/farmacologia , Integração Viral/efeitos dos fármacos , Sequência de Aminoácidos , Avaliação Pré-Clínica de Medicamentos , HIV-1/genética , HIV-2/efeitos dos fármacos , HIV-2/enzimologia , HIV-2/genética , Vírus da Imunodeficiência Felina/efeitos dos fármacos , Vírus da Imunodeficiência Felina/genética , Integrases , Dados de Sequência Molecular , Vírus da Leucemia Murina de Moloney/efeitos dos fármacos , Vírus da Leucemia Murina de Moloney/enzimologia , Vírus da Leucemia Murina de Moloney/genética , Oligopeptídeos/síntese química , Retroviridae/efeitos dos fármacos , Retroviridae/enzimologia , Retroviridae/genética , Relação Estrutura-Atividade
15.
Proc Natl Acad Sci U S A ; 91(23): 11138-42, 1994 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-7972024

RESUMO

The generation of diverse chemical libraries using a "libraries from libraries" concept is described. The central features of the approaches presented are the use of well-established solid-phase synthesis methods for the generation of combinatorial libraries, combined with the chemical transformation of such libraries while they remain attached to the solid support. The chemical libraries that are generated by this process have very different physical, chemical, and biological properties compared to the libraries from which they were derived. A wide range of chemical transformations are possible for peptide-based or other libraries, and an almost unlimited range of useful chemical diversities can be envisioned. In the example presented, the amide functionalities in an existing combinatorial library made up of peptides were permethylated while the library remained attached to the solid-phase support used in its synthesis. After removal of the permethylated mixtures from their solid support, this library, now lacking the typical -CONH- amide bonds of peptides, can be tested in solution with virtually all existing assay systems to identify individual compounds having specific biological activities of interest. An illustration of the use of such libraries is presented, in which the described permethylated library was used to identify individual permethylated compounds having potent antimicrobial activity against Gram-positive bacteria.


Assuntos
Antibacterianos/química , Peptídeos/química , Sequência de Aminoácidos , Antibacterianos/síntese química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Metilação , Dados de Sequência Molecular , Peptídeos/síntese química , Resinas Vegetais , Estereoisomerismo
16.
Antimicrob Agents Chemother ; 38(10): 2280-6, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7840558

RESUMO

The use of water-soluble synthetic peptide combinatorial libraries permits the systematic examination of tens to hundreds of millions of peptides in existing microdilution assays. In the present study, we prepared and determined the antistaphylococcal activities of two new synthetic peptide combinatorial libraries (one N-acetylated, the other not) composed of tetrapeptides having one position defined and the remaining three positions made up of mixtures of L-, D-, and unnatural amino acids (a total of 58 different amino acids). These libraries, when used in conjunction with an iterative selection process, allowed for the development of a series of individually defined tetrapeptides with high levels of activity against Staphylococcus aureus. The activities of the final individual peptides against two additional strains of gram-positive bacteria (methicillin-resistant S. aureus and Streptococcus sanguis), a gram-negative bacterium (Escherichia coli), as well as the yeast Candida albicans were also determined. Cell viability assays showed that the identified peptides are bacteriostatic against both S. aureus and E. coli.


Assuntos
Antibacterianos/farmacologia , Oligopeptídeos/farmacologia , Sequência de Aminoácidos , Escherichia coli/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Staphylococcus aureus/efeitos dos fármacos
17.
J Virol ; 68(3): 1342-9, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8107199

RESUMO

Neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) vary widely and have not been reproducibly associated with prognosis or disease progression. We have found that both low-passage clinical isolates and laboratory-adapted strains of HIV-1 have different sensitivities to neutralization by the same antiserum, depending on the host cell in which the viral stock is prepared. One such isolate (VL069) grown in H9 cells was neutralized by 20 human sera at a geometric mean titer of 1:2,047; this same isolate prepared in peripheral blood mononuclear cell (PBMC) culture was neutralized at a mean titer of < 1:10 by the same sera. Adsorption and mixing experiments indicated that neither antibody to H9 cell components nor blocking by excess viral antigen was responsible for the differences observed. This host cell effect is rapidly reversible upon passage of the virus from PBMCs to H9 cells and back into PBMCs. In contrast, the neutralization characteristics remained remarkably stable over extended culture in PBMCs. Two laboratory strains and five clinical isolates were evaluated in expanded studies of this phenomenon. While the neutralization characteristics of most of the strains studied were affected by the host cell in which the strain was propagated, two of the strains (one clinical isolate and one laboratory strain) appeared antigenically unaffected by their cell of origin. Host cell effect was also evident in neutralization by monoclonal antibodies directed against the CD4-binding region and the V2, V3, and gp41 regions. Possible mechanisms for this host cell effect include (i) mutation during passaging; (ii) selection in different host cells of different subpopulations of the (uncloned) viral stock; and (iii) cell-specific posttranslational modifications. To explore these possibilities, the V3 through V5 region of gp120 was sequenced in preparations made by passing VL069 into H9 cells and into PBMCs; HIVMN grown in CEM-SS cells and in PBMCs was also sequenced. In both cases, a few amino acid changes outside the V3 region were found. Studies are currently under way to assess the significance of these changes.


Assuntos
Anticorpos Anti-HIV/imunologia , HIV-1/crescimento & desenvolvimento , HIV-1/imunologia , Testes de Neutralização , Adaptação Biológica , Sequência de Aminoácidos , Anticorpos Monoclonais , Células Cultivadas , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp41 do Envelope de HIV/genética , Proteína gp41 do Envelope de HIV/imunologia , Humanos , Dados de Sequência Molecular , Inoculações Seriadas , Especificidade da Espécie , Cultura de Vírus
18.
Ophthalmology ; 100(8): 1268-71, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8341513

RESUMO

BACKGROUND: Argon laser suture lysis has been effectively used in the early post-operative period to enhance filtration after trabeculectomy. The most substantial reductions in intraocular pressure (IOP) occur when laser suture lysis is performed during the first 2 postoperative weeks, and virtually no effect has been reported after the fourth postoperative week. Mitomycin C, used as adjunct therapy, improves the success rate of trabeculectomy in high-risk eyes and may change the time course for effective suture lysis. METHODS: The authors used late laser suture lysis in five high-risk patients after mitomycin C trabeculectomy. The mean patient age was 66.8 +/- 15.7 years, and laser suture lysis was performed an average of 13 +/- 5.8 weeks (range, 7-21 weeks) after surgery. RESULTS: The mean IOP before suture lysis was 20.2 +/- 3.8 mmHg. The average IOP reduction immediately after suture lysis was 11.4 +/- 3.9 mmHg. The average IOP 3 to 4 months after laser suture lysis was 9.4 +/- 3.4 mmHg. CONCLUSION: The authors postulate that adjunctive mitomycin C therapy markedly delays wound healing and appears to extend the period that laser suture lysis is clinically effective.


Assuntos
Glaucoma/cirurgia , Terapia a Laser , Trabeculectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pressão Intraocular , Masculino , Mitomicina/administração & dosagem , Cuidados Pós-Operatórios , Esclera/cirurgia , Retalhos Cirúrgicos , Suturas
19.
Pediatr Infect Dis J ; 12(4): 326-9, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8483627

RESUMO

During two outbreaks of respiratory syncytial virus (RSV) infection, 68 children with acute respiratory illnesses were cultured for RSV using a Rhino-Probe (RP) nasal curette and either a nasopharyngeal (NP) swab or a nasal wash (NW). In the first outbreak isolations of RSV by the RP nasal curette and NP swab methods were compared. RSV was cultured from 25 of 42 (60%) subjects using the RP nasal curette and from 20 of 42 (48%) subjects using the NP swab. In the second outbreak the RP nasal curette and the NW collection techniques were compared. RSV was isolated from 15 of 26 (58%) children evaluated. RSV was cultured from 14 of 15 (93%) patients by RP and 13 of 15 (87%) when using NW. In the group of culture-positive subjects, the TESTPACK RSV rapid antigen test was positive in 10 of 15 (67%) using the RP and in 6 of 15 (40%) using the NW. Like the NP swab the RP nasal curette was simple, noninvasive and relatively inexpensive, yet it was as sensitive as the NW for detection of RSV.


Assuntos
Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/microbiologia , Infecções por Respirovirus/diagnóstico , Manejo de Espécimes/instrumentação , Doença Aguda , Surtos de Doenças , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
20.
Ophthalmic Surg ; 23(5): 364-6, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1603543

RESUMO

We investigated the effect of the angle orientation of the probe during Nd:YAG transscleral cyclophotocoagulation. We found, based on histologic evaluation of the ciliary processes and surrounding structures, that the angle at which the probe was placed on the eye was critical. A probe angulation as little as 15 degrees off the perpendicular destroyed sites less than optimal for achieving the goal of decreasing aqueous humor production.


Assuntos
Corpo Ciliar/cirurgia , Fotocoagulação/métodos , Humor Aquoso/metabolismo , Corpo Ciliar/patologia , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...