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HSV-1716 is a replication-restricted, neuroattenuated ICP 34.5 gene mutant of herpes simplex virus type 1 (HSV-1). Because of the attenuated phenotype of ICP 34.5 mutants in rodent models of HSV disease, they have been promoted as potential vaccine strains and gene therapy vectors and have been used by us and others as therapeutic agents for the treatment of experimental malignant tumors. However, all data on the phenotype of HSV-1716 and other ICP 34.5 mutants are from animal model systems, while humans are the natural hosts of HSV-1. To achieve an initial characterization of the phenotype of 1716 in human tissue, we have studied its replication in mature human skin xenografts on SCID mice. We find that replication of 1716 is severely restricted in such human skin grafts relative to both parental wild-type HSV-1 strain 17+ and the HSV-1716 revertant virus 1716R, in which the 759-bp ICP 34.5 gene deletions have been repaired. Moreover, the replication of both 1716 and 17+ is significantly better in the human skin grafts than it is in mouse skin. The implications of these findings are discussed.  相似文献   

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Laboratory cultures of house dust mites Dermatophagoides pteronyssinus (Trouessart, 1897) and Dermatophagoides farinae Hughes, 1961 were used to study the population dynamics of the mites and the kinetics of antigen appearance. The analysis of extracts obtained after different incubation periods, carried out by SDS-PAGE, immunoblotting, and enzyme-linked immunosorbent assay, allows for the definition of 3 different growth phases: the latency phase (F1); the exponential growth phase (F2) during which the allergenic proteins, including the Der 1 and Der 2 major allergens, were expressed more intensely and in larger quantities; and a final phase (F3), death, in which the lowest rates of allergenic components with a clearly different pattern were seen. The data obtained from this work demonstrates that mite cultures during the maximum growth phase (F2) contain the largest amount of allergenic components as well as the highest major allergen concentrations.  相似文献   

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我国拥有丰富的钛、钨、钼矿产资源,是世界钛、钨、钼初级产品的主要生产和出口国,为加快发展其深加工产品,调整产业结构和产品结构,变资源优势为产业优势和经济优势,建议利用国债资金支持几个对其产业结构调整有重大影响的深加工产品生产建设项目,并提出了国家有关部门当前应立即开展的几项工作的建议。  相似文献   

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Recently, evidence has been presented that nitric oxide (NO) modulates myocardial contraction induced by beta-adrenergic stimulation in vitro and in vivo. In this study, we investigated whether inhibition of the L-arginine NO system augments the positive inotropic response of the left ventricle to direct stimulation of the sympathetic nerves in vivo in the dog. Electrical stimulation was applied to the left stellate ganglion (LSG) for 1 min at submaximal (5 V, 2.5, 5 and 10 Hz) and supramaximal intensities (10 V, 10 Hz) in twelve anesthetized and vagotomized dogs. Next, in the same dogs, N(omega)-nitro L-arginine methylester (L-NAME) was infused into the left anterior descending (LAD) coronary artery, and LSG stimulation repeated using the same protocol. Finally, L-arginine was infused into the LAD artery, and LSG stimulation repeated. We used the maximum of the first derivative of left ventricular pressure (LV max d P/dt) as an index of the myocardial contractility. Plasma epinephrine and norepinephrine concentrations were measured in the coronary sinus at 5 V, 2.5 Hz before and after L-NAME treatment in five of twelve dogs. L-NAME treatment significantly augmented the inotropic response of the left ventricle (percent change in the LV max dP/dt) to LSG submaximal stimulation trains from 164 +/- 13 to.212 +/- 21 (P < 0.03), from 187 +/- 15 to 234 +/- 25 (P < 0.05) and from 220 +/- 19 to 280 +/- 33% (P < 0.05), respectively. This response was reversed by L-arginine treatment. However, the inotropic response to the supramaximal stimulation train did not change after L-NAME and L-arginine treatment. L-NAME significantly increased plasma norepinephrine concentration from 0.69 +/- 0.41 to 1.00 +/- 0.52 ng/ml without changing plasma epinephrine concentration in the coronary sinus. It is concluded that the inhibition of the L-arginine NO system augmented the positive inotropic effect on the left ventricle during sympathetic nerve stimulation in normal dogs in vivo.  相似文献   

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Magnesium deficiency is associated with increased contractility of smooth muscle cells. Since contractility of bronchial smooth muscle is important in patients with asthma, magnesium deficiency could negatively influence the clinical condition. We wanted to assess whether magnesium deficiency exists in patients with asthma. Extracellular (plasma) and intracellular (erythrocytes and mononuclear leucocytes) concentrations of magnesium were determined in 20 mildly symptomatic patients with asthma and compared to 20 healthy controls. In asthmatic patients, the mean +/- SD magnesium level in plasma was 0.81 +/- 0.05 mmol.l-1, in erythrocytes 0.20 +/- 0.02 fmol.cell-1, and in mononuclear leucocytes 5.10 +/- 2.55 fmol.cell-1; these values did not differ significantly from those of the healthy controls: 0.79 +/- 0.06 mmol.l-1, 0.19 +/- 0.02 fmol.cell-1, and 4.61 +/- 1.75 fmol.cell-1, respectively. No evidence for the existence of a magnesium deficit needing chronic magnesium supplementation was, thus, found in these patients.  相似文献   

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Nitrogen dioxide (NO2) is one of a number of nitrogen compounds that are by-products of combustion and occur in domestic environments following the use of gas or other fuels for heating and cooking. In this study, we examined the effect of two levels of NO2 on symptoms, lung function and airway hyperresponsiveness (AHR) in asthmatic adults and children. In addition, in the same subjects, we examined the effects of the same levels of NO2 mixed with combustion by-products from a gas space heater. The subjects were nine adults, aged 19-65 yrs, and 11 children, aged 7-15 yrs, with diagnosed asthma which was severe enough to require daily medication. All subjects had demonstrable AHR to histamine. Exposures were for 1 h on five separate occasions, 1 week apart, to: 1) ambient air, drawn from outside the building; 2) 0.3 parts per million (ppm) NO2 in ambient air; 3) 0.6 ppm NO2 in ambient air; 4) ambient air+combustion by-products+NO2 to give a total of 0.3 ppm; and 5) ambient air+combustion by-products+NO2 to give a total of 0.6 ppm. Effects were measured as changes in lung function and symptoms during and 1 h after exposure, in AHR 1 h and 1 week after exposure, and in lung function and symptoms during the week following exposure. Exposure to NO2 either in ambient air or mixed with combustion by-products from a gas heater, had no significant effect on symptoms or lung function in adults or in children. There was a small, but statistically significant, increase in AHR after exposure to 0.6 ppm NO2 in ambient air. However, there was no effect of 0.6 ppm NO2 on AHR when the combustion by-products were included in the test atmosphere nor of 0.3 ppm NO2 under either exposure condition. We conclude that a 1 h exposure to 0.3 or 0.6 ppm NO2 has no clinically important effect on the airways of asthmatic adults or children, but that 0.6 ppm may cause a slight increase in airway hyperresponsiveness.  相似文献   

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BACKGROUND: Eosinophils are increased in the airways and blood of asthmatic patients. However, the mechanism of regulation of eosinophilia is incompletely understood. METHODS: To study the potential effect of asthmatic lymphocytes on eosinophils, lymphocytes from the blood of asthmatic patients in exacerbation, or from healthy subjects, were isolated and cultured in medium alone (LC-CM) or with interleukin-2 (IL-2-CM) (125 U/ml), and the effect of supernatant obtained from these cultures on eosinophil proliferation from progenitors and survival was studied. RESULTS: IL-2-CM from asthmatic patients significantly increased eosinophil colony formation from asthmatic blood but had no effect on colony formation from the blood of healthy subjects. IL-2-CM from asthmatic patients also significantly prolonged the survival of eosinophils. IL-2 alone and IL-2-CM from healthy subjects had no effect on eosinophil proliferation and survival. Asthmatic lymphocytes had more IL-2 receptors (CD25) than normal lymphocytes, and this difference persisted even after culture in IL-2. However, upregulation of the CD25 receptor on normal lymphocytes by incubation with concanavalin A led to the production of IL-2-CM, which did not increase eosinophil proliferation from progenitors. CONCLUSIONS: Lymphocytes from asthmatic patients but not from normal blood can significantly increase eosinophil proliferation and survival. The effects on eosinophil proliferation do not seem to be directly related to the presence of increased CD25 expression on lymphocytes.  相似文献   

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BACKGROUND: The usefulness and safety of the analysis of blood inflammatory markers in asthma are widely recognized. Recently, the analysis of induced sputum has been proposed as a safe, non-invasive tool in the study of airway inflammation in asthma. OBJECTIVE: Our aim was to test whether sputum analysis is more useful than blood analysis in the evaluation of airway inflammation in untreated and treated asthmatic patients. METHODS: Twelve untreated patients with mild to moderate asthma underwent a methacholine challenge test, sputum induction and blood sampling. A group of 14 normal subjects was also evaluated for baseline comparison. The same evaluation was repeated after 3 months of budesonide treatment. Before and after treatment, we tested the relationship of eosinophilic markers in induced sputum and blood with clinical and functional data. We also compared eosinophilic markers in induced sputum with the same markers in blood. RESULTS: Untreated patients showed a significant relationship between sputum eosinophils and symptom score, and between sputum eosinophilic cationic protein and symptom score, FEV1 and PD20FEV1. No relationship between blood eosinophilic markers and clinical or functional data was observed. In budesonide-treated patients, both sputum and blood eosinophils were significantly lower than in untreated patients, but eosinophil decrease was greater in sputum than in blood. Sputum eosinophilic proteins were also significantly lower in treated patients, whereas serum eosinophilic proteins were low at baseline and remained unchanged after treatment. Sputum eosinophilic markers were lower in normal subjects than in both untreated and treated patients, while blood eosinophils, but not serum eosinophilic cationic protein, were lower in normals than in untreated patients. CONCLUSIONS: The analysis of induced sputum is more useful than the analysis of blood in the evaluation of asthma severity and of the effect of glucocorticoid treatment in patients with mild to moderate asthma.  相似文献   

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Salmeterol and formoterol are two long-acting beta2-agonists for inhalation, currently being used in clinical practice. The aim of the present study was to investigate the onset of action, duration of effect and potency of these two beta2-agonists in asthmatic patients. Patients (n=28) were included on the basis of salbutamol stepwise reversibility (100, 100 and 200 microg, given cumulatively; total reversibility > or =15%). In a double-blind placebo-controlled crossover study, the bronchodilating properties of formoterol 6, 12 and 24 microg were compared with the effects of salmeterol 50 microg. Formoterol was given via Turbuhaler and salmeterol via Diskhaler, and forced expiratory volume in one second (FEV1) was monitored during 12 h. Formoterol at all doses had a more rapid onset than salmeterol as judged from bronchodilation at 3 min after the dose. Formoterol at all doses had a similar duration of effect to salmeterol 50 microg, as judged from bronchodilation at 12 h after dose administration. When the relative potency of the two drugs was compared, salmeterol 50 microg was estimated to correspond to formoterol 9 microg (95% confidence interval: 3-19 microg). We confirm that formoterol and salmeterol are both long-acting beta2-agonists, but with some differences in effect profile. We confirm the more rapid onset of action of formoterol compared with salmeterol, and furthermore, no difference in duration of effect is evident.  相似文献   

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As far as we know, IgA and IgG antibodies to purified house dust mite allergens Der fI and Der fII in nasal secretions have never been documented. Therefore, we determined specific IgA, SIgA and IgG antibodies (abs) to crude extract of D. farinae and its purified allergens Der fI and der f II in nasal secretions collected by aspiration from 34 normal subjects, 25 untreated nasal allergic patients and 28 treated nasal allergic patients on parenteral immunotherapy by means of an avidin-biotin ELISA. The following results were obtained. (1) The specific IgA, SIgA and IgG abs to each of the three kinds of allergens correlated with each other. The groups of patients with nasal allergy (both treated and untreated) showed higher levels of specific IgA, SIgA and IgG abs to the allergens than the normal group. (2) In the group of treated patients, the levels of specific abs were not correlated with the clinical improvement of symptoms or the degree of response to nasal challenge. (3) The treated patients failed to show significantly higher levels of abs in nasal secretions than the untreated patients. (4) The specific IgA and SIgA abs in nasal secretions seemed to be predominantly produced locally, and IgG abs might be transudated from the circulation.  相似文献   

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Dermatitis or inflammation of the skin caused by an outside agent, is a condition with many causes. It may result from direct irritation of the skin by a substances (chemical or insecticide) or it may be an allergic reaction to a particular substance that has been in contact with the skin as soap or detergent or insect urticating hairs; injected as insect saliva or faeces or sting or taken by mouth as food or drug. In general, treatment of dermatitis depends mainly upon the cause. In the present study, three species of mites were isolated from the dust collected from houses of atopic dermatitis patients. These mites were Dermatophagoides pteronyssinus, Ornithonyssus bacoti and Haemogamasus pontiger. The former species was the predominant one which is known to produce the most potent allergen. It was concluded that house dust mites are one of the aetiological factors of atopic dermatitis and that genera of mites other than Dermatophagoides may be considered as allergen in house dust mites.  相似文献   

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In 565 patients with acute myocardial infarction admitted to a coronary care unit within 12 hours of the onset of symptoms, serum potassium level was determined on admission. The incidence of dysrhythmias occurring during the first 12 hours was referred to the initial serum potassium level. Hypopotassemia (less than or equal to 3.5 mmol/l) was seen in 9.2% and associated with a significantly higher incidence of ventricular arrhythmias in 33% as compared to 18% in the control group. Especially ventricular fibrillation was significantly more frequent in the hypokalaemic (14%) than in the normokalaemic (3%) patients (P less than 0.01). Hyperpotassemia (less than or equal to 5.1 mmol/l) was found in 6% with a higher incidence of second and third degree AV block and left-bundle branch block. This group was much more prone to severe haemodynamic complications and therefore had a bad prognosis with a high clinic mortality of 53%. There was no relation between supraventricular arrhythmias, sinuatrial bradyarrhythmias and intraventricular block other than left bundle branch block to serum potassium level.  相似文献   

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