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1.
The human plasma contains small peptide molecules known as low molecular weight growth factors synergistically increasing certain biological actions of insulin-like growth factors. In the present work we isolated and characterized a hexapeptide with HWESAS as structure. This purified peptide was absolutely necessary for the sulfation activity of insulin-like growth factor-I on chick embryo pelvic cartilages and improved the mitogenic activity of both insulin-like growth factors. The effects of this hexapeptide were confirmed by using the homologous synthetic peptide, that exhibited similar biological effects. Other synthetic peptides with structure derived from hexapeptide were shown to be active: the pentapeptide HWESA appeared more potent than the tripeptide HWE, which is about 170 to 200 times less active than the hexapeptide. The sequence of hexapeptide HWESAS is identified in only one human protein that is C3f, a fragment of C3 complement.  相似文献   

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High-level penicillin resistance in pneumococci is due to alterations in penicillin-binding proteins (PBPs) 2X, 2B, and 1A. We have sequenced the penicillin-binding domain of PBP 1A from penicillin-resistant South African pneumococcal isolates and have identified amino acid substitutions which are common to all the resistant isolates analyzed. Site-directed mutagenesis was then used to determine whether particular amino acid substitutions at specific positions in PBP 1A mediate penicillin resistance. PCR was used to isolate PBP 2X, 2B, and 1A genes from clinical isolate 8303 (penicillin MIC, 4 micrograms/ml). These wild-type PBP genes were cloned into pGEM-3Zf and were used as the transforming DNA. Susceptible strain R6 (MIC, 0.015 microgram/ml) was first transformed with PBP 2X and 2B DNA, resulting in PBP 2X/2B-R6 transformants for which MICs were 0.25 microgram/ml. When further transformed with PBP 1A DNA, 2X/2B/1A-R6 transformants for which MICs were 1.5 micrograms/ml were obtained. Site-directed mutagenesis of the PBP 1A gene from isolate 8303 was then used to reverse particular amino acid substitutions, followed by transformation of PBP 2X/2B-R6 transformants with the mutagenized PBP 1A DNA. For PBP 2X/2B/1A-R6 transformants, the introduction of the reversal of Thr-371 by Ser or Ala in PBP 1A decreased the MIC from 1.5 to 0.5 micrograms/ml, whereas the reversal of four consecutive amino acid substitutions (Thr-574 by Asn, Ser-575 by Thr, Gln-576 by Gly, and Phe-577 by Tyr) decreased the MIC from 1.5 to 0.375 micrograms/ml. These data reveal that amino acid residue 371 and residues 574 to 577 of PBP 1A are important positions in PBP 1A with respect to the interaction with penicillin and the development of resistance.  相似文献   

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PURPOSE: To assess multivoxel proton MR spectroscopy combined with MR imaging and hemodynamic MR imaging in the evaluation of brain tumors in children and young adults. METHODS: Fifteen patients with brain tumors and 10 healthy children underwent MR imaging and MR spectroscopy on a 1.5-T system. Ten patients with tumors had both MR spectroscopy and hemodynamic MR imaging. MR spectroscopy data sets with 1 cm3 to 3.4 cm3 resolution were acquired within 8.5 minutes by using a point-resolved spectroscopic, chemical-shift imaging technique in two dimensions with volume preselection. MR imaging was performed using fast spin-echo techniques. Hemodynamic MR imaging data were acquired every 2.5 seconds at one anatomic level using a spoiled gradient-echo sequence during intravenous bolus administration of contrast material. RESULTS: Assessment with multivoxel MR spectroscopy and hemodynamic MR imaging added about 30 minutes to the total MR examination time. Normal tissue exhibited spectral peaks from biologically significant compounds such as N-acetylaspartate (NAA), choline-containing compounds (Cho), and total creatine (tCr). Twelve biopsy-proved tumors exhibited prominent Cho, reduced NAA, variable tCr, and/or lactate or lipids, and two showed increased hemodynamic parameters. Three of the tumors treated with radiation did not reveal prominent levels of Cho. Tissue necrosis had no Cho, NAA, or tCr, and reduced hemodynamics. CONCLUSIONS: Preliminary findings by MR spectroscopy combined with MR imaging and hemodynamic MR imaging suggest that regions of active tumor may be differentiated from areas of normal tissue and areas of necrosis. These findings may enable metabolic and hemodynamic characterization of childhood brain tumors as well as suggest their response to therapy.  相似文献   

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Progress has been made in the identification of experimental and analytical procedures that allow for a more reliable determination of equilibrium and kinetic constants. Possible origins of the frequently observed deviations of the measured binding progress from that expected for chemical binding of pseudo-first order, and appropriate experimental controls have been proposed. Improved analytical approaches include the application of global analysis and analytical corrections for the influence of mass transport.  相似文献   

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The purpose of this exploratory investigation was to evaluate the heuristic potential of 31P magnetic resonance spectroscopy (MRS) in elucidating a neurobiologic component of the liability for a substance use disorder (SUD). We investigated 31P MRS spectra employing chemical shift imaging (CSI) derived from four distinct anatomic brain locations (i.e. frontal, occipital, right parietal, left parietal) in three groups of peripubertal children who are hypothesized to be at increasing levels of familial SUD risk. Specifically, we studied children with a positive paternal family history of SUD and a disruptive behavior disorder (DBD) diagnosis (SUD+/DBD+; n = 10), in contrast, to those with a positive paternal SUD history in the absence of other psychopathology (SUD+/DBD-; n = 13) and matched control children from normal families (SUD-/DBD-; n = 13). In addition, we examined neurocognitive tests of our subjects to determine any associations between cognitive capacities with regional 31P MRS spectra. The highest-risk sample (SUD+/DBD+) demonstrated a diminished proportion of phosphodiesters confined to the right parietal voxel. This right parietal phosphodiester proportion correlated only with the Information Scale score on a standard intelligence test for children. This suggested a relationship between general learning ability and motivation for academic achievement and right parietal physiology in the highest-risk sample. Variations in synaptic pruning could account for this observation.  相似文献   

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PURPOSE: Endothelin-1 (ET-1), a peptide produced by the vascular endothelium, causes profound renal vasoconstriction by binding to ET-A receptors. The present study examined the renal actions of ET-1 after ET-A receptors were blocked by BE-18257B to unmask the functions of ET-B receptors. MATERIALS AND METHODS: Renal hemodynamics and clearance measurements were obtained in anesthetized dogs after intrarenal infusion of BE-18257B at 100 ng./kg./min. (Group 1), after intrarenal infusion of ET-1 at 2 ng./kg./min. (Group 2), or after intrarenal infusion of ET-1 superimposed on BE-18257B (Group 3). RESULTS: In Group 1, BE-18257B infusion did not alter arterial pressure, renal blood flow (RBF), GFR or tubular function. In Group 2, ET-1 infusion led to a significant decrease in RBF and GFR (37 and 40%, respectively) without altering arterial pressure. Urinary volume and sodium excretion were not changed but osmolality decreased significantly. In Group 3, BE-18257B infusion significantly attenuated the decrease in RBF caused by ET-1 and increased GFR by 40% without altering arterial pressure, associated with significant diuresis and natriuresis. CONCLUSION: Renal vasoconstriction caused by ET-1 is attenuated by ET-A receptor blockade with BE-18257B, which unmasks the hemodynamic and tubular actions of ET-B receptors. As a result, it limits the ET-1 induced decrease in RBF and raises GFR, and leads to a diuresis and natriuresis.  相似文献   

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BACKGROUND: Optical coherence tomography (OCT) is a novel technique for noninvasive cross-sectional imaging with high spatial resolution (10 to 20 microm). OCT is similar to B-mode ultrasound except that it uses infrared light rather than ultrasound. We studied OCT imaging of the gastrointestinal (GI) tract in vitro to analyze the potential of this technique for endoscopic applications. METHODS: Human gastrointestinal tissues harvested from surgical resection and autopsy specimens were used. Specimens were imaged within 5 hours of resection or snap frozen in liquid nitrogen. After imaging, OCT scan locations were carefully marked using dye microinjections, fixed, and prepared for routine histologic processing. OCT images were then compared and correlated with the histologic sections. RESULTS: OCT images demonstrated clear delineation of the mucosa and submucosa in most specimens. Furthermore, microscopic structures such as crypts, blood vessels, or esophageal glands in the submucosa and lymphatic nodules were observed. CONCLUSIONS: The resolution of OCT images of GI wall is sufficient to delineate the microscopic structure of the mucosa and submucosa. Potentially, OCT would allow in vivo imaging at endoscopy of the microstructure of the mucosa and submucosa. This would be particularly useful in the detection and staging of small lesions such as early stage cancers.  相似文献   

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BACKGROUND AND PURPOSE: Current indications for carotid endarterectomy are determined by balancing the relative risks of surgery with the benefits of reduced risk of subsequent stroke. Our purpose was to use MR perfusion imaging to assess patients being considered for carotid endarterectomy and to monitor sequential changes in MR perfusion characteristics after surgery. In particular, we wished to determine whether this technique could be used to detect changes that might be related to post-carotid endarterectomy hyperemia. METHODS: We used a single-section gradient-recalled echo sequence to investigate 14 patients being examined before possible surgery for carotid artery disease. In the 12 patients in whom carotid endarterectomy was performed, sequential studies were performed 3 to 5 days after surgery and at 3 months. Analysis of bolus-arrival-time (BAT) images was performed. RESULTS: Significant delays in preoperative BAT images of 0.89 seconds (range, 0.05 to 3.22 seconds) were apparent between hemispheres. Excluding the two patients with contralateral internal carotid artery (ICA) occlusion, early arrival, possibly indicating postoperative hyperemia, was seen in five patients immediately after carotid endarterectomy but resolved within 3 to 5 months after surgery. CONCLUSION: MR perfusion imaging shows differences in BAT between hemispheres in patients with ICA stenosis. Changes in perfusion characteristics after carotid endarterectomy are complex, and early BAT on the operative side can occur soon after endarterectomy in over half those patients without an occluded contralateral vessel. The significance of these findings with regard to patient outcome and risk of postoperative hyperemia requires further investigation.  相似文献   

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The ABC Schizophrenia Study, a large-scale epidemiological and neurobiological research project commenced in 1987, initially pursued two aims: (1) to elucidate the possible causes of the sex difference in age at first admission for schizophrenia and (2) to analyse the early course of the disorder from onset until first contact and its implications for further course and outcome. First, transnational case-register data (for Denmark and Germany) were compared, second, a population-based sample of first-episode cases of schizophrenia (n = 232) were selected and third, the results obtained were compared with data from the WHO Determinants of Outcome Study by using a systematic methodology. A consistent result was a 3-4 years higher age of onset for women by any definition of onset, which was not explainable by social variables, such as differences in the male-female societal roles. A sensitivity-reducing effect of oestrogen on central D2 receptors was identified as the underlying neurobiological mechanism in animal experiments. Applicability to humans with schizophrenia was established in a controlled clinical study. A comparison of familial and sporadic cases showed that in cases with a high genetic load, the sex difference in age of onset disappeared due to a clearly reduced age of onset in women, whereas in sporadic cases it increased. To analyse early course retrospectively, a semistructured interview, IRAOS, was developed. The early stages of the disorder were reconstructed in comparison with age- and sex-matched controls from the same population of origin. The initial signs consisted mainly of negative and affective symptoms, which accumulated exponentially until the first episode, as did the later emerging positive symptoms. Social disability appeared 2-4 years before first admission on average. In early-onset cases, social course and outcome, studied prospectively over 5 years, was determined by the level of social development at onset through social stagnation. In late-onset cases, decline from initially high social statuses occurred. Socially negative illness behaviour contributed to the poor social outcome of young men. Symptomatology and other proxy variables of the disorder showed stable courses and no sex differences. Further aspects tested were the sequence of onset and the influence of substance abuse on the course of schizophrenia, primary and secondary negative symptoms, structural models and symptom clusters from onset until 5 years after first admission.  相似文献   

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Magnetic resonance imaging (MRI) was evaluated for its potential in assessment of acute pancreatitis compared to computed tomography (CT). 15 patients with acute pancreatitis were examined using a routine protocol including T1- and T2-weighted sequences and a fat-suppressed T1-weighted spin-echo sequence. Gadopentant-Dimeglumin (Gd-DTPA) was given. For comparison, plain and contrast-enhanced CT was performed prior to MRI. MRI proved to be superior to CT in detection of bleeding, duodenitis and ascites. MRI failed to detect concrements. These first results show that, considering the latest development in technology, MRI is not inferior to CT in diagnostic imaging of acute pancreatitis.  相似文献   

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We present an automated, knowledge-based method for segmenting chest computed tomography (CT) datasets. Anatomical knowledge including expected volume, shape, relative position, and X-ray attenuation of organs provides feature constraints that guide the segmentation process. Knowledge is represented at a high level using an explicit anatomical model. The model is stored in a frame-based semantic network and anatomical variability is incorporated using fuzzy sets. A blackboard architecture permits the data representation and processing algorithms in the model domain to be independent of those in the image domain. Knowledge-constrained segmentation routines extract contiguous three-dimensional (3-D) sets of voxels, and their feature-space representations are posted on the blackboard. An inference engine uses fuzzy logic to match image to model objects based on the feature constraints. Strict separation of model and image domains allows for systematic extension of the knowledge base. In preliminary experiments, the method has been applied to a small number of thoracic CT datasets. Based on subjective visual assessment by experienced thoracic radiologists, basic anatomic structures such as the lungs, central tracheobronchial tree, chest wall, and mediastinum were successfully segmented. To demonstrate the extensibility of the system, knowledge was added to represent the more complex anatomy of lung lesions in contact with vessels or the chest wall. Visual inspection of these segmented lesions was also favorable. These preliminary results suggest that use of expert knowledge provides an increased level of automation compared with low-level segmentation techniques. Moreover, the knowledge-based approach may better discriminate between structures of similar attenuation and anatomic contiguity. Further validation is required.  相似文献   

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OBJECTIVE: To describe the characteristics of and trends in nosocomial infection among human immunodeficiency virus (HIV)-infected patients. DESIGN: Multicenter prospective cohort study. SETTING/PATIENTS: HIV-infected patients were enrolled at time of first inpatient admission at five Veterans' Administration Medical Centers (VAMCs). RESULTS: As of March 1995, 2,541 patients with 6,625 inpatient admissions had been monitored in the five VAMCs. A total of 530 nosocomial infections were detected using standard Centers for Disease Control and Prevention definitions. Overall distribution by infection site was 31% for primary bloodstream infections (BSIs), 28% for urinary tract infections, 15% for pneumonia, and 26% for all other sites. Of BSIs, 63% were central line-associated bloodstream infections (CLABs). The rate of CLABs per 1,000 central line days was 6.5 (range, 2.3-8.3) for all patients from participating hospitals, similar to the median CLAB rate of 6.0 for patients in medical intensive-care units (ICUs) of National Nosocomial Infections Surveillance (NNIS) System hospitals from January 1990 through September 1994. For ICU-specific CLABs, the rate from hospitals reporting at least one ICU CLAB was 12.7 (range, 12.1-13.1), comparable to the 90th percentile of NNIS hospital medical ICUs (13.1). Staphylococcus aureus, associated with 35% of BSIs, was the most common nosocomial BSI pathogen. Our data demonstrated the following: 13 (10%) of 134 patients with CD4 counts > or = 200 cells/mm3 had a CLAB, compared with 61 (6%) of 1,011 patients with CD4 counts < 200 cells/mm3, P = .08; the per-day risk of CLABs did not change with increased duration of catheterization (P = .4); and the per-day risk of a temporary (ie, short-term) CLAB was greater than that of a permanent CLAB (P < .001). CONCLUSIONS: The data suggest that HIV-infected patients were at higher risk of acquiring a BSI than were patients in the NNIS population; patients with CD4 counts > or = 200 cell/mm3 and temporary central lines were at increased risk for BSI, perhaps reflecting widespread prophylaxis with trimethoprim-sulfamethoxazole among patients with CD4 counts < 200 cells/mm3, and, in contrast to most studies, S aureus, not coagulase-negative Staphylococcus, was the most common BSI pathogen.  相似文献   

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PURPOSE: The ability of magnetic resonance (MR) angiography to depict visceral and renal vessels was evaluated in patients with abdominal aortic aneurysms (AAAs). PATIENTS AND METHODS: MR sequences (sagittal T1-weighted, two-dimensional coronal, and three-dimensional axial time-of-flight) were compared in a prospective blinded fashion with conventional angiograms obtained preoperatively in 23 patients with AAAs. Results were correlated with surgical findings when available. RESULTS: Operative aortic clamp site was correctly predicted with conventional angiography in 95% of patients and with MR angiography in 86% (P > .1). Aneurysm neck measurements obtained with the two modalities were within 1 cm in 91% of cases. With conventional angiography as the standard of reference, 96% of all renal arteries were identified on MR angiograms but 36% of accessory arteries were missed. MR angiography enabled identification of patients who had at least one renal artery stenosis greater than 50% with a sensitivity of 100% and specificity of 89%. For identifying individual renal artery, celiac artery, and superior mesenteric artery stenoses of similar severity, the sensitivity and specificity were 67% and in excess of 96%, respectively. The celiac artery could not be evaluated in one case. CONCLUSION: The results of this small study suggest that the role of MR angiography in the preoperative evaluation of AAA warrants further investigation.  相似文献   

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The objective of this study was to try to identify, by pretreatment screening, a group of patients at higher risk of developing endometrial carcinoma on tamoxifen. Between January 1993 and January 1997, 360 postmenopausal patients with breast cancer were enrolled in this prospective study. Basal screening included gynaecologic examination with a Papanicolaou smear and endovaginal sonography. In the case of an abnormal ultrasound (endometrial thickness greater than 4 mm), an outpatient hysteroscopy with an endometrial biopsy was carried out. These examinations were repeated annually. By means of this preliminary evaluation, two groups of patients were identified: patients without initial lesions (group I) and patients with initial endometrial lesions (group II). These two groups of patients were followed up separately exactly in the same way. Endometrial lesions taken into account were: adenocarcinomas (in situ and invasive), polyps with or without atypia, myomas and adenomyotic lesions with irregular mucosa. After 3 years and after 4 years of follow-up, the percentage of atypical lesions was significantly higher in the group with initial lesions than in the group without initial lesions. This study suggests that a group of high risk patients more sensitive to the carcinogenic effect of tamoxifen can be identified by pretreatment evaluation.  相似文献   

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PURPOSE: This study was undertaken to examine the relationship between intraoperative color-flow duplex (CFD) findings and the development of restenosis in patients undergoing carotid endarterectomy (CEA). METHODS: Seventy-eight patients (43 male and 35 female; mean age, 65 years) underwent 86 CEAs (eight staged bilateral) and intraoperative CFD during a 31-month period. Three patients (three CEAs, 3%) underwent both CFD and a completion arteriographic scan. Patients were observed in a postoperative protocol using CFD surveillance. The follow-up interval ranged from 6 to 24 months (average, 12 months). RESULTS: After undergoing CEA, 10 patients (10 CEAs, 11%) had an abnormality detected by intraoperative CFD; one was confirmed with a completion arteriographic scan. These abnormalities consisted of elevated peak systolic velocities (PSV) with a mosaic color pattern suggesting turbulence seen in six CEAs, including one internal carotid artery (ICA) with abnormal hemodynamics and an unremarkable completion arteriogram. Intimal defects on B-mode were seen in another four CEAs. These carotid arteries were reexplored, defects (intimal flaps with platelet thrombus) were confirmed by direct examination, and all were repaired with or without a patch (six ICAs, three external carotid arteries, and one common carotid artery). No cerebrovascular events occurred in the perioperative period. No carotid restenosis (> or = 50% diameter reduction) was identified during follow-up of 43 patients (48 CEAs, 56%). Two patients had recurrent neurologic symptoms. CONCLUSION: Intraoperative CFD is an effective test for detecting flow abnormalities or intimal defects in patients undergoing CEA. Ensuring normal intraoperative hemodynamics after CEA may be a major factor associated with decreased incidence of perioperative cerebrovascular events and subsequent carotid artery restenosis.  相似文献   

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针对亚微米尺度晶体元器件在加工和服役中出现的反常力学行为和动态变形等问题,基于离散位错动力学理论建立了单晶铜塑性变形过程的二维离散位错动力学模型。该模型考虑外加载荷、位错间相互力和自由表面镜像力对位错的作用机制,引入了截断位错速度准则。与微压缩实验对比验证了模型的正确性,并且能够描述力加载描述的位错雪崩现象。应用该模型分析了不同加载方式和应变率下位错演化及力学行为,结果表明:当外部约束为力加载和位移加载时,应力应变曲线分别呈现出台阶状的应变突增和锯齿状的应力陡降,位错雪崩效应的内在机制则分别归结为位错速度的随机性和位错源开动的间歇性;应变率在102~4×104 s?1范围内,单晶铜屈服应力的应变率敏感性发生改变,位错演化特征由单滑移转变为多滑移面激活的均匀变形,位错增殖逐渐代替位错源激活作为流动应力的主导机制。   相似文献   

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