RESUMEN
BACKGROUND: Extensive drainage of peatlands in the southeastern United States coastal plain for the purposes of agriculture and timber harvesting has led to large releases of soil carbon as carbon dioxide (CO2) due to enhanced peat decomposition. Growth in mechanisms that provide financial incentives for reducing emissions from land use and land-use change could increase funding for hydrological restoration that reduces peat CO2 emissions from these ecosystems. Measuring soil respiration and physical drivers across a range of site characteristics and land use histories is valuable for understanding how CO2 emissions from peat decomposition may respond to raising water table levels. We combined measurements of total soil respiration, depth to water table from soil surface, and soil temperature from drained and restored peatlands at three locations in eastern North Carolina and one location in southeastern Virginia to investigate relationships among total soil respiration and physical drivers, and to develop models relating total soil respiration to parameters that can be easily measured and monitored in the field. RESULTS: Total soil respiration increased with deeper water tables and warmer soil temperatures in both drained and hydrologically restored peatlands. Variation in soil respiration was more strongly linked to soil temperature at drained (R2 = 0.57, p < 0.0001) than restored sites (R2 = 0.28, p < 0.0001). CONCLUSIONS: The results suggest that drainage amplifies the impact of warming temperatures on peat decomposition. Proxy measurements for estimation of CO2 emissions from peat decomposition represent a considerable cost reduction compared to direct soil flux measurements for land managers contemplating the potential climate impact of restoring drained peatland sites. Research can help to increase understanding of factors influencing variation in soil respiration in addition to physical variables such as depth to water table and soil temperature.
RESUMEN
Malignant pleural mesothelioma (MPM) is an aggressive tumour with a limited response to conventional therapy. The aim of this study was to evaluate the anticancer effect of a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-azaCdR), and two histone deacetylase inhibitors, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA). Human mesothelioma cells were treated with each epigenetic drug, either alone or in combinations. The cytotoxic effects on treated cells and the expression of specific tumour antigens were evaluated. The recognition of treated cells by a specific CD8+ T-cell clone was also measured. Additionally, the effect of combined treatments was tested in a murine model of mesothelioma. We showed that VPA and SAHA synergised with 5-azaCdR to kill MPM cells and induce tumour antigen expression in the remaining living tumour cells. As a consequence, tumour cells expressing these antigens were recognised and lysed by specific CD8+ cytotoxic T-cells. In vivo, treatment with 5-azaCdR/VPA inhibited tumour growth, and promoted lymphocyte infiltration and an immune response against tumour cells. Appropriate epigenetic drug combinations, in addition to inducing mesothelioma cell death, also affect the immunogenic status of these cells. This property could be exploited in clinical investigations to develop MPM treatments combining chemotherapeutic and immunotherapeutic approaches.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Azacitidina/análogos & derivados , Metilasas de Modificación del ADN/administración & dosificación , Inhibidores de Histona Desacetilasas/administración & dosificación , Mesotelioma/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológico , Linfocitos T Citotóxicos/inmunología , Ácido Valproico/administración & dosificación , Animales , Antígenos de Neoplasias/inmunología , Azacitidina/administración & dosificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Decitabina , Sinergismo Farmacológico , Humanos , Ácidos Hidroxámicos/administración & dosificación , Proteínas de la Membrana/inmunología , Mesotelioma/inmunología , Mesotelioma/patología , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , Neoplasias Pleurales/inmunología , Neoplasias Pleurales/patología , Linfocitos T Citotóxicos/efectos de los fármacos , VorinostatRESUMEN
Human T cell hybridomas were established by fusion of PHA-activated PBL with the 8-azaguanine resistant human T-leukemic cell line CEM-CM3. High levels of B cell growth factor (BCGF) activity were detected in the supernatants of hybridoma C8-2B2 and its subclones. Hybridoma C8-2B2, in addition to the Leu 3a, also expressed the OKT11 surface marker which was not detectable on the parent CEM-CM3 cells. BCGF from the culture supernatant was purified by combined use of salt fractionation and gel filtration to 36.6 fold with 23.9% recovery of activity. The BCGF produced by hybridoma C8-2B2 has a molecular weight range of 16,000-20,000 in two major electrophoretically different forms with pI values of 6.4 and 7.4.
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Sustancias de Crecimiento/biosíntesis , Hibridomas/metabolismo , Linfocinas/biosíntesis , Linfocitos T/metabolismo , Antígenos de Diferenciación de Linfocitos T , Antígenos de Superficie/análisis , Linfocitos B/citología , Línea Celular , Sustancias de Crecimiento/aislamiento & purificación , Humanos , Interleucina-2/análisis , Interleucina-4 , Punto Isoeléctrico , Linfocinas/aislamiento & purificación , Linfocitos T/inmunologíaRESUMEN
The effects of Isoprinosine (ISO) on interleukin-2 (IL-2) production by human peripheral blood mononuclear cells (PBMC) were investigated. Treatment (of human PBMC) with ISO enhanced IL-2 production by PBMC from 7 of 10 normal individuals. However, no augmentation of IL-2 production was observed when cultures of HUT-78 cells, a human leukemic T cell line, were treated with ISO. IL-2 purified from supernatants of human PBMC treated with ISO exhibited pI values of 5.5 and 6.4. IL-2 prepared from untreated PBMC exhibited a single pI value of 8.2. The pI value of IL-2 prepared from ISO-treated PBMC shifted to 8.2 after treatment with neuraminidase, demonstrating that the IL-2 molecules isolated from ISO-treated PBMC possessed sialic acid. The pI values of the IL-2 isolated from ISO-treated and untreated HUT-78 culture supernatants were identical (pI = 7.8) and were not modified by neuraminidase treatment. These results suggest that the increase in IL-2 production following treatment of PBMC with ISO may be mediated through the activation of a distinct subset of IL-2 producing cells. Furthermore, the sialylation of IL-2 may be of physiologic and immunopharmacologic importance.
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Inosina Pranobex/farmacología , Inosina/análogos & derivados , Interleucina-2/biosíntesis , Ácidos Siálicos/metabolismo , Adyuvantes Inmunológicos/farmacología , Adulto , Línea Celular , Células Cultivadas , Cromatografía de Afinidad/métodos , Medios de Cultivo/análisis , Humanos , Interleucina-2/aislamiento & purificación , Focalización Isoeléctrica , Lectinas/farmacología , Leucemia/sangre , Linfocitos/clasificación , Linfocitos/metabolismo , Neuraminidasa/farmacologíaRESUMEN
Left ventricular hypertrophy (LVH) is frequently associated with hypertension and constitutes a major cardiovascular risk factor, the reduction of which should be considered when initiating antihypertensive therapy. To assess the effects of indapamide on LVH, 18 hypertensive patients were included in the study (11 men and 7 women, age 53.6 +/- 2.9 years, mean +/- standard deviation) whose supine diastolic blood pressure was greater than 95 mm Hg without (n = 11) or with (n = 7:6 beta blockers, 1 calcium antagonist) antihypertensive therapy. All presented with LVH, echocardiographically defined by a left ventricular mass index greater than 110 g/m2. After a 2-week preinclusion period, all patients received indapamide, 2.5 mg/day, for a period of 6 months. Physical examination including blood pressure measurement was performed on selection (M-1/2), before (M0), and after 1 (M1), 3 (M3) and 6 (M6) months of indapamide treatment, and echocardiography was performed at M0 and M6. Quality of life was evaluated by means of questionnaires completed by the patient and the physician, and a visual analog scale was completed by the patient at M-1/2, M0 and M6. All clinical parameters remained stable during the 2-week preinclusion period. Indapamide administration induced a highly significant reduction in both supine systolic and diastolic blood pressures from 173.9 +/- 2.9/100.5 +/- 1.2 mm Hg at M0 to 150.9 +/- 1.9/90.5 +/- 1.3 mm Hg at M1 (p less than 0.001), and 145.0 +/- 1.7/86.0 +/- 1.5 mm Hg at M6 (p less than 0.001). Similar favorable effects were observed in the upright position.(ABSTRACT TRUNCATED AT 250 WORDS)
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Cardiomegalia/tratamiento farmacológico , Diuréticos/uso terapéutico , Corazón/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Indapamida/uso terapéutico , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Ecocardiografía , Femenino , Estudios de Seguimiento , Corazón/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos , Humanos , Masculino , Persona de Mediana Edad , Miocardio/patología , Calidad de VidaRESUMEN
A multicenter study was performed to assess the efficacy and the acceptability of indapamide in hypertensive patients previously untreated, or treated and unsatisfactorily controlled with either angiotensin-converting enzyme (ACE) inhibitor or beta-blocking therapy. Four centers participated in the study, which included patients whose supine diastolic blood pressure was between 95 and 115 mmHg with no treatment (group I, n = 40), those taking captopril (group II, n = 40) or those taking propranolol (group III, n = 40). After a 2-week single-blind placebo run-in period, patients received indapamide either alone (group I) or in combination with the previous therapy (groups II and III) for 4 months. Blood pressure, heart rate, weight, and clinical and biochemical acceptability were measured before and after 2 and 4 months of treatment. At the same time points, quality of life was determined using standardized questionnaires completed by the patient (20 items) and the physician (10 items) and a visual analog scale completed by the patient. In all groups, administration of indapamide induced a clinically and statistically significant reduction in both systolic and diastolic blood pressures in the supine position after 2 months. Indapamide alone controlled blood pressure in 82% of the patients previously untreated, and indapamide in combined therapy controlled blood pressure, respectively, in 67 and 85% of patients previously uncontrolled with ACE inhibitors or beta blockers. In all groups, questionnaires on quality of life showed a progressive and significant improvement in general well-being. After 4 months of treatment, the percentage of improvement in the physician questionnaire was 77.1% in group I, 60.6% in group II and 71.4% in group III.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Captopril/uso terapéutico , Diuréticos/uso terapéutico , Hipertensión/tratamiento farmacológico , Indapamida/uso terapéutico , Propranolol/uso terapéutico , Calidad de Vida , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Captopril/administración & dosificación , Comportamiento del Consumidor , Combinación de Medicamentos , Tolerancia a Medicamentos , Femenino , Grecia , Humanos , Indapamida/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Placebos , Postura , Propranolol/administración & dosificación , Método Simple CiegoRESUMEN
Forty-four patients undergoing abdominal aortic surgery and twenty-eight patients undergoing carotid surgery were randomly treated with different anticoagulant regimens. During surgery, an unfractionated heparin (UFH) intravenous bolus of 50 IU/kg was compared with a low molecular weight heparin (LMWH) bolus of either 120 IU/kg, 80 IU/kg, 40 IU/kg or 20 IU/kg. Six hours after surgery and for 48 hours, an UFH infusion was compared with an LMWH infusion of either 10,000 IU/day or 6,000 IU/day and then, a single LMWH subcutaneous injection of 3,075 IU was administered. Heparin activity was measured by factor Xa inhibitor and by prolongation of APTT which were studied 15, 30 and 60 minutes after cross-clamping, at the end of surgery and six hours later, and on days 1, 2, 3 and 6. After a descriptive analysis of clinical and pharmacokinetic profiles of each regimen, optimal LMWH treatment is proposed.
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Anticoagulantes/uso terapéutico , Aorta Abdominal/cirugía , Arterias Carótidas/cirugía , Heparina de Bajo-Peso-Molecular/uso terapéutico , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
A 16-year-old girl had hearing loss, paroxysmal tremor, gait disorders, and psychiatric disturbances as the initial manifestations of a cryptococcal meningoencephalitis. Imaging demonstrated an obstructive hydrocephalus, and neuro-otological explorations showed a retrocochlear deafness and diffuse brainstem involvement. Emphasis is on the deafness, which rarely occurs as a presenting symptom in this condition, and on its dramatic improvement following antimycotic therapy.
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Criptococosis/complicaciones , Pérdida Auditiva/etiología , Meningoencefalitis/complicaciones , Adolescente , Femenino , HumanosRESUMEN
Left ventricular hypertrophy is a major and independent cardiovascular risk factor in hypertension. The effects of a diuretic, indapamide, on the regression of left ventricular hypertrophy were studied in a group of 9 patients with mild hypertension treated in an open therapeutic trial over a 12 month period. At the end of the trial, the left ventricular mass index decreased significantly from 172 +/- 11 to 147 +/- 11 g/m2 (p less than 0.001). Therefore, in contrast to the other diuretics which have been studied, indapamide seems able to induce regression of the left ventricular hypertrophy complicating hypertension.
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Cardiomegalia/tratamiento farmacológico , Hipertensión/complicaciones , Indapamida/uso terapéutico , Adulto , Anciano , Cardiomegalia/etiología , Evaluación de Medicamentos , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
The genetic polymorphism of human alpha 2-HS glycoprotein was studied by ultrathin-layer isoelectric focusing in a pH range 4.2-4.9 followed by immunoblotting using antisera specific for the protein. Three common phenotypes, HSGA1-1, HSGA2-2, and HSGA1-2, were easily recognized using this technique. Each homozygous phenotype was constituted by five major bands with different pI's, and the heterozygous phenotype represented an exact combination of each of them. After removal of sialic acid, each homozygous pattern was resumed in a single band, which differed in charge between HSGA1 and HSGA2. Asialo-heterozygous HSG1-2 combined the two bands characteristic of each allele product. Family studies are in agreement with an autosomal codominant transmission of the two alleles. Population studies indicate that the frequency of the HSGA1 and 2 alleles are .65 and .35, respectively.
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Proteínas Sanguíneas/genética , Polimorfismo Genético , Proteínas Sanguíneas/aislamiento & purificación , Cruzamientos Genéticos , Femenino , Humanos , Inmunoensayo , Focalización Isoeléctrica , Masculino , Neuraminidasa , alfa-2-Glicoproteína-HSRESUMEN
Klebsiella pneumoniae isolates were recovered in increased numbers from oysters harvested during the warm months of the year from approved and classified waters. A total of 76 oyster isolates was examined using in vivo and in vitro assays. The nonpathogenic responses of the strains studied suggest that environmental strains are not a public health risk.
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The expression of CD3 molecules by the lymphocytes of five patients with ataxia-telangiectasia was examined using the murine monoclonal antibody OKT3. By immunofluorescent staining, fewer of the patients' peripheral blood mononuclear cells and purified T cells expressed CD3 compared with normals. The proliferative response of the patients' cells to OKT3 was also less than normal. However, the mononuclear cells from all five patients produced IL-2 after OKT3 stimulation; in four patients IL-2 was normal, while one patient produced greater than normal levels. While the expression of cellular IL-2 receptors and the release of these receptors into culture supernatants was generally less in ataxia-telangiectasia patients, the levels of receptor expression were not significantly less than normal. As analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis, the CD3 molecules from ataxia-telangiectasia patients' lymphocytes were no different from those of normal individuals. These results suggest that patients with ataxia-telangiectasia have structurally normal CD3 molecules which may be used to activate cells normally for some but not all T cell functions.
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Antígenos de Diferenciación de Linfocitos T/inmunología , Ataxia Telangiectasia/inmunología , Adolescente , Adulto , Anticuerpos Monoclonales , Niño , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Interleucina-2/biosíntesis , Interleucina-2/inmunología , Activación de Linfocitos , Masculino , Fitohemaglutininas/farmacología , Receptores Inmunológicos/análisis , Receptores de Interleucina-2 , Linfocitos T/inmunologíaRESUMEN
Purified Alternaria alternata altertoxins I, II, and III were evaluated for comparative cytotoxicity and ability to inhibit gap junction communication in the Chinese hamster lung metabolic cooperation assay. The noncytotoxic test range for each altertoxin was determined for the metabolic communication assays: altertoxin I, 1, 2, 3, 4, 5 micrograms/ml; altertoxin II, 0.02, 0.008, 0.006, 0.004, 0.002, 0.0008 micrograms/ml; and altertoxin III, 0.2, 0.1, 0.08, 0.06, 0.04 micrograms/ml. Altertoxin II was the most cytoxic in the V79 system, followed by altertoxins III and I. The last cytotoxic of the three, altertoxin I, weakly disrupted metabolic communication at two concentrations (4 and 5 micrograms/ml). Altertoxins III and II did not significantly inhibit gap junction communication more than the weak tumor promoter 4-O-methyl ether tetradecanoylphorbol 13-acetate.
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Alternaria/metabolismo , Benzo(a)Antracenos/toxicidad , Pulmón/efectos de los fármacos , Hongos Mitospóricos/metabolismo , Micotoxinas/toxicidad , Animales , Comunicación Celular/efectos de los fármacos , Células Cultivadas , Cricetinae , Fibroblastos/efectos de los fármacos , Uniones Intercelulares/efectos de los fármacos , Pulmón/metabolismo , Perileno/análogos & derivadosRESUMEN
Binding studies with [3H] 25-(OH) D3 were performed under a variety of conditions using Gc (Vitamin D-binding protein) purified from individuals displaying different phenotypes. No significant differences in affinity of binding were found between Gc1f, Gc1s and Gc2 allelle products in either homozygous or heterozygous individuals, nor between Gc1 anodal and Gc1 cathodal isotypes. Affinity was not significantly affected by different reaction temperatures (4, 22 or 37 degrees C), the presence or absence of Ca2+ ions, and binary and ternary interactions with G-actin and G-actin-DNase complexes respectively. However, reduction of pH caused a progressive decrease in binding with virtual abolition at pH less than or equal to 5.0. The latter might promote dissociation of D3 metabolites from Gc carrier protein in acidic compartments of cells.
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Calcifediol/metabolismo , Variación Genética , Proteína de Unión a Vitamina D/genética , Heterocigoto , Homocigoto , Humanos , Cinética , Fenotipo , Valores de Referencia , Proteína de Unión a Vitamina D/sangre , Proteína de Unión a Vitamina D/aislamiento & purificaciónRESUMEN
Penicillium expansum 1071, 1172, NRLL 973, and Penicillium patulum ATCC 24550 were inoculated into Red Delicious, Golden Delicious, and McIntosh apples. The decayed tissue was trimmed from the sound tissue, each fraction was weighed, and the patulin concentration in the juice was assayed by thin layer chromatography. The quantity of patulin in the whole apples and in decayed tissues was calculated and these values were used to determine the percentage of total patulin removed by trimming. The patulin content ranged from 140 to 4880 mug/apple. Trimming removed 93-99% of the total patulin, regardless of incubation temperature, fungus strain, or apple variety. Trimming of defective tissue from fungus-rotted apples could substantially reduce the patulin concentration.
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Contaminación de Alimentos/prevención & control , Frutas , Patulina , Piranos , Microbiología de Alimentos , Industria de Procesamiento de Alimentos , Métodos , Penicillium/metabolismoRESUMEN
Pathogenic Vibrio cholerae 0-Group 1 survived for more than 3 weeks in artificial sea water with little loss in viability. Live oysters placed in such contaminated, artificial sea water took up but did not concentrate V. cholerae . Heat treatments provided by an in-can pasteurization process and by preparation of naturally contaminated oysters according to common recipes effectively reduced the numbers of V. cholerae by 5 logs/g.
RESUMEN
Intrathecal synthesis of interferon gamma was shown in 14 out of 16 samples of cerebrospinal fluid collected in the first days of disease in adults, children, and newborn infants with herpes encephalitis. This synthesis was concomitant with that of interferon alpha and was switched off when the specific antibodies in the central nervous system increased. No endogenous interferon gamma was detected in 11 serum samples or 13 samples of cerebrospinal fluid collected early in the course of the disease from patients with measles encephalitis and rubella encephalitis, or in serum and cerebrospinal fluid samples from seven patients with subacute sclerosing panencephalitis. In serum collected after the 10th day after the onset of neurological symptoms interferon gamma was present at low concentrations in only three out of 11 serum specimens from patients with measles encephalitis or rubella encephalitis. Interferon gamma was present in patients with acute herpes encephalitis and there was active virus replication, but it was not present in postinfectious encephalitis. Possibly the local production of specific antibodies masks the viral antigens and switches off the induction of interferons.