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1.
BACKGROUND: Combinatorial chemistry has become an important method for identifying effective ligand-receptor binding, new catalysts and enzyme inhibitors. In order to distinguish the most active component of a library or to obtain structure-activity relationships of compounds in a library, an efficient quantitative assay is crucial. Electrospray mass spectrometry has become an indispensable tool for qualitatively screening combinatorial libraries and its use for quantitative analysis has recently been demonstrated. RESULTS: This paper describes the use of quantitative electrospray mass spectrometry for screening libraries of inhibitors of enzymatic reactions, specifically the enzymatic glycosylation by beta-1,4-galactosyltransferase, which catalyzes the transfer of galactose from uridine-5'-diphosphogalactose to the 4-position of N-acetylglucosamine beta OBn (Bn: benzene) to form N-acetyllactosamine beta OBn. Our mass spectrometric screening approach showed that both nucleoside diphosphates and triphosphates inhibited galactosyltransferase while none of the nucleoside monophosphates, including uridine-5'-monophosphate, showed any inhibition. Additional libraries were generated in which the concentrations of the inhibitors were varied and, using mass spectrometry, uridine-5'-diphosphate-2-deoxy-2-fluorogalactose was identified as the best inhibitor. CONCLUSIONS: This report introduces quantitative electrospray mass spectrometry as a rapid, sensitive and accurate quantitative assaying tool for inhibitor libraries that does not require a chromophore or radiolabeling. A viable alternative to existing analytical techniques is thus provided. The new technique will greatly facilitate the discovery of novel inhibitors against galactosyltransferase, an enzyme for which there are few potent inhibitors.  相似文献   

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Organ transplant recipients on immunosuppressive therapy are prone to skin cancers, especially squamous cell carcinomas developing on sun-exposed areas. Their frequency increases with time after transplantation reaching 40-70% of the patients after 20 years. Squamous cell carcinomas tend to be multiple and may have a life-threatening course. Most studies concern kidney transplant recipients but new data are now available on recipients of other organs. Carcinogenic factors include mainly immunosuppressive treatments, UV light and human papillomaviruses; the role of genetic factors is more equivocal. Melanomas and other rare tumors such as Merkel cell tumors or sarcomas are also increased. Surgical excision with histological examination represents the treatment of choice. When lesions become multiple and/or aggressive, additional therapeutic methods are necessary, such as topical or oral retinoids and in some cases, reduction of the immunosuppressive treatment. Radiotherapy should be reserved to limited cases. Prevention must be undertaken by a regular dermatological examination and sun protection.  相似文献   

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Williams syndrome first described in 1961 is generally characterised by mental deficiency, gregarious personality, unusual "elfin" facies, supravalvular aortic stenosis and idiopathic infantile hypercalcaemia. Patients with Williams syndrome show a hemizygous submicroscopic deletion of 7q11.23 detectable by fluorescent in-situ hybridisation (FISH). The deleted portion of the chromosome corresponds to the Elastin gene. We report 3 girls with characteristics of Williams syndrome in whom the diagnosis was confirmed by demonstration of the hemizygous deletion of 7q11.23 in the karyotype by FISH. These patients, aged 6, 7 and 10 years, showed the characteristic facies and gregarious personalities. Some developmental delay with mild mental deficiency and dysmorphic facies were prominent features in the initial presentation. Cardiac lesions found in these patients were small patent ductus arteriosus which closed, pulmonary valvular stenosis and mitral valve prolapse associated with mitral regurgitation respectively. Hypercalcaemia was not documented in these patients. Learning difficulty was a major issue and all patients required special schooling. Chromosome analyses done on peripheral blood were found to be normal in all patients. FISH using the Elastin Williams Syndrome Chromosome Region (WSCR) probes (oncor) showed the hemizygous deletion of 7q11.23. Diagnosis of Williams syndrome can now be confidently confirmed with the help of FISH.  相似文献   

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Red cell aggregation has been studied by photometry in 47 children with insulin-dependent diabetes mellitus. The disease was associated with boosting of reversible red cell aggregation, which was most of all expressed during metabolic decompensation with ketoacidosis. When metabolic subcompensation was attained, this parameter did not completely normalize and still had to be corrected.  相似文献   

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Two hundred and thirty consecutive adult patients underwent open heart surgery at Ramathibodi Hospital from January 1, 1994 to December 31, 1995. The patients were categorised into 4 groups, A, B, C and D; consisting of 52 (22.4%) with adult congenital heart disease, 121 (52.2%) with acquired valvular heart disease 52 (22.4%) with coronary heart disease and 7 (3%) with diseases of the aorta. The mortality in various groups were analyzed separately each year, in 1994 and 1995. The overall mortality, in adult congenital heart disease, was 5.7 per cent consisting of acquired valvular heart disease (6.6%), coronary artery disease (CAD) (3.8%) and diseases of the aorta (14.2%). We found that the incidence of CAD and the patients underwent CABG were increasing. The overall mortality for open heart surgery in adults was 6 per cent. Though the number of patients who underwent open heart surgery did not truly represent all heart diseases, trends of coronary artery disease seem to be increasing. Risk factors of coronary artery disease and low mortality from CABG might be the main reasons that CABG has increased obviously.  相似文献   

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OBJECTIVE: To modify the classic fetal biophysical profile (FBP) with the aim of obtaining rapid and accurate information about actual fetal condition in non-compromised fetuses with a subsequent favorable outcome and to be suitable for a number of outclinic patients. METHODS: Four-hundred and ninety-four fetuses from singleton pregnancies in two randomized groups were monitored by the modified FBP (mFBP) and 168 of them after the external vibratory acoustic stimulation (VAS/mFBP). The mFBP was characterized by two main characteristics: non-stress test was excluded and the testing was finished at the moment when all of the three fetal biophysical activities became normal. The external VAS was applied only in cases with no evidence of fetal activity at the start of the FBP. RESULTS: Of the examined fetuses, 326 fetuses in the control group were monitored by the mFBP and there were 316 (96.9%) favorable outcomes and 10 (3.1%) adverse perinatal outcomes. The sensitivity, specificity and positive and negative predictive values of the mFBP score in predicting adverse perinatal outcome were 60, 99, 66.7 and 98.7%, respectively. In the study group of 168 fetuses there were 165 (98.2%) favorable outcomes and three (1.8%) adverse perinatal outcomes. The sensitivity, specificity and positive and negative predictive values of the VAS/mFBP were 66.7, 100, 100 and 99.4%, respectively. The efficiency of the VAS/mFBP in predicting perinatal mortality alone was even higher. After the external VAS and the first 5 min of the modified testing approximately two-fifths (41.8%) of healthy fetuses with a subsequent good outcome exhibited normal in all of the three biophysical activities and approximately two-thirds (65.5%) of them after 10 min. In the VAS/mFBP group of healthy fetuses, during the same time periods, normal breathing movements were observed in 72% and 87% of fetuses, respectively. CONCLUSIONS: According to our results the mFBP and particularly the VAS/mFBP antenatal protocol as a new and rational variant of the FBP could improve fetal assessment allowing in cases of non-compromised fetuses rapid and accurate information about actual fetal well-being. Because of its high accuracy and a reduced testing time the antepartal method with observation of fetal breathing movements after VAS is becoming acceptable as a screening of fetal well-being evaluation in outclinic conditions.  相似文献   

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Accumulating evidence suggests that altered DNA methylation may play a role in the oncogenesis of human neoplasms, including lung cancer. The presence of aberrant hypermthylations at 3p, 9p, 11p, ad 17p, which are known to be hot spots for allele loss in lung cancers, is suggested to be a reflection of the existence of tumor suppressor genes in these chromosomal regions. In the present study, we investigated the methylation status of the Rb locus at 13q14 as well as that of the bcl-2 locus at 18q21 in 134 lung cancer specimens, representing all major histological subtypes. As a result, 18q21 was identified to be the fifth chromosomal region affected by frequent tumor-specific aberrant hypermethylation in lung cancers. The occurrence of aberrant hypermethylation at the bcl-2 locus at 18q21 was restricted to non-small cell lung cancers, and among non-small cell lung cancers, such epigenetic aberrations were observed most frequently in adenocarcinomas without any association with bcl-2 expression. Interestingly, allelic loss at the bcl-2 locus was also seen in 40% (7 of 17 informative cases) of adenocarcinomas; this frequency was also the highest among values for the various histological subtypes of lung cancers. These results suggest that aberrant hypermethylation at the bcl-2 locus may be a reflection of a putative tumor suppressor gene residing at 18q21, and aberrant hypermethylation might play a role in its inactivation. In contrast, altered methylation status of the Rb locus appears to be quite rare in lung cancers, if present at all.  相似文献   

9.
As assisted reproductive technology is being developed, in vitro fertilization and embryo transfer (IVF-ET) are the treatments of choice for many infertility problems. The outcome of pregnancies achieved by IVF-ET is different from that of spontaneous pregnancies. In this retrospective study, the outcome of pregnancies from 400 IVF treatment cycles performed from October 1991 to October 1994 were reported. There were 80 pregnancies (20% per oocyte retrieval, 21.9% per embryo transfer) with an increased rate of abortion (30%), multiple pregnancy (20%), ectopic pregnancy (6.25%), heterotopic pregnancy (1.25%), preterm delivery (11.8%), low birth weight (35.8%) and cesarean section (62.7%). This study shows that the complication rate of pregnancies from IVF-ET cycles was higher than that found in spontaneous pregnancies. Some complications such as multiple pregnancies may be prevented by limiting the number of transferred embryos. From this study, all IVF-ET pregnancy should be considered as high risk pregnancies.  相似文献   

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1. Cats with one cochlea destroyed were trained to localize sound. After behavioral measures of the animal's accuracy of localization were made, cortical auditory areas were ablated unilaterally. 2. The results showed: a) like binaural localization, monaural localization of sound in space, as measured by the ability of an animal to move toward a sound source, depends on integrity of auditory cortex; b) it is only ablation of cortex contralateral to the functional ear that seriously affects localizing behavior; ablation of cortex ipsilateral to the intact cochlea has little or no effect on localizing behavior. 3. To explain the results, we suggest that auditory cortex is essential for an organized perception of space including the relation of the animal's position to other objects in space. We also suggest that auditory cortex contralateral to a given ear is necessary in order for the animal to recognize that a stimulus is presented to that ear of, when both ears are intact, to recognize that the stimulus to the given ear differs in some way (intensity, time of arrival, sequential arrangement of sounds) from the stimulus to the opposite ear.  相似文献   

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The aim of this article is to share good practice with interested professionals contemplating setting up a hospital at home scheme. The authors present an overview of the relevant research literature and describe their own experiences of developing the scheme in Bromsgrove.  相似文献   

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The international normalized ratio (INR) is the current standard for monitoring anticoagulation therapy. Although simple to determine, it normally requires venipuncture and extensive laboratory resources for specimen handling and analysis. The portable capillary whole blood coagulation monitor is an alternative to laboratory venipuncture. Its promoted advantages are: it obtains a blood sample by finger-stick versus venipuncture; rapid turnaround time for results; resultant dosage adjustments (as appropriate) performed in minutes versus hours or days after testing; relative ease of use by nonlaboratory personnel; and potential for home monitoring. This project compared the results of INRs obtained through the venipuncture/laboratory process to INRs obtained by the portable monitoring process at the National Naval Medical Center. A correlation coefficient of 0.97 was determined. The difference in the mean INR results of the two testing methods was not clinically significant (p = 0.269). The portable monitor was determined to be a viable alternative to laboratory testing.  相似文献   

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Nd-Yag laser endobronchial therapy has been available at Green Lane Hospital since 1993. During this time 34 patients have received a total of 45 treatments; 12 were referred from other centres. Relief of dyspnoea or haemoptysis, as a result of malignant airway disease, was the most common indication for therapy (20/34). Tracheal webs (post-tracheostomy) were the most common benign lesion treated (4/34). There were no perioperative deaths and only one major complication, a postoperative pneumomediastinum. Two patients with malignant disease undoubtedly had improved survival but most patients had significant palliation of symptoms without clear survival benefit. Three patients had airway stents placed postoperatively. Laser endobronchial therapy is safe and offers useful palliation and occasionally definitive therapy for a variety of airway diseases.  相似文献   

20.
We studied the incidence of infection with Helicobacter pylori in Panamanians with chronic dyspepsia, gastric or duodenal ulcer, gastritis or gastric cancer. The histopathology was positive in 54 (81%) of 66 patients; the urea test was positive in 52 (82.5%) of 63 cases; the impromptu was positive in 51 (79.6) of 64 patients; the endoscopic examination was positive in 64 (82.9%) of 77 examinations.  相似文献   

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