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RS Morrison JC Ahronheim GR Morrison E Darling SA Baskin J Morris C Choi DE Meier 《Canadian Metallurgical Quarterly》1998,15(2):91-101
BACKGROUND: Protein kinases play a central role in controlling diverse signal transduction pathways in all cells. The identification of the direct cellular substrates of individual protein kinases remains the key challenge in the field. RESULTS: We describe the protein engineering of v-Src to produce a kinase which preferentially uses an ATP analog, N6-(benzyl) ATP, as a substrate, rather than the natural v-Src substrate, ATP. The sidechain of a single residue (Ile338) controls specificity for N6-substituted ATP analogs in the binding pocket of v-Src. Elimination of this sidechain by mutation to glycine produces a v-Src kinase which preferentially utilizes N6-(benzyl) ATP as a phosphodonor substrate. Our engineering strategy is generally applicable to the Src family kinases: mutation of the corresponding residue (Thr339 to glycine) in the Fyn kinase confers specificity for N6-(benzyl) ATP on Fyn. CONCLUSIONS: The v-Src tyrosine kinase has been engineered to exhibit specificity for an unnatural ATP analog, N6-(benzyl) ATP, even in a cellular context where high concentrations of natural ATP are present (1-5 mM), where preferential use of the ATP analog by the mutant kinase is essential. The mutant v-Src transfers phosphate more efficiently with the designed unnatural analog than with ATP. As the identical mutation in the Src-family kinase Fyn confers on Fyn the ability to recognize the same unnatural ATP analog, our strategy is likely to be generally applicable to other protein kinases and may help to identify the direct targets of specific kinases. 相似文献
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Both regional analgesia and systemic opioid therapy (e.g. PCA) are commonly used for pain relief following thoracic surgery. Many anaesthesiologists are reluctant to use thoracic epidural analgesia on general surgical wards. Therefore, we investigated in a prospective randomised study the efficacy of intercostal blocks (ICB) or interpleural analgesia (IPA) compared to PCA with systemic opioids (PCA). Following ethics committee approval and informed consent, 45 thoracotomy patients were randomised for postoperative pain management: group 1: intravenous PCA with piritramide (PCA-control), group 2: intercostal blocks of the segments concerned with 5 ml bupivacaine 0.5% at the end of surgery and 6 hours thereafter (ICB), group 3: interpleural analgesia with 20 ml bupivacaine 0.25% applied every 4 hours using a catheter placed during surgery near the apex of the pleural space (IPA). Patients in the ICB and IPA groups were able to obtain additional pain relief by PCA with piritramide. Alternative medication for all groups in case of insufficient analgesia was metamizol. Both regional analgesia groups used significantly less piritramide up to the 3rd (IPA) or 7th (ICB) postoperative day than the control group (p < 0.05). The consumption of metamizol was lower as well (n. s.). No significant differences between the study groups were observed with regard to pain scores (visual analogue scale VAS) at rest, during deep inspiration, coughing or mobilisation. Respiratory parameters as forced vital capacity, forced expiratory volume (1 sec) and peak flow (FVC; FEV1; PF) were reduced significantly following thoracotomy and showed a slow restitution in all three study groups without major inter-group differences. Intercostal blocks and interpleural analgesia significantly reduce opioid demand following thoracotomy and are effective means of postoperative pain management. Nevertheless, in contrast to epidural analgesia, both methods have to be supplemented by, or combined with, systemic analgesics in most patients. On the other hand, compared to epidural analgesia, ICB and IPA are less invasive and easier to manage on general surgical wards. 相似文献
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The large majority of patients being managed in palliative medicine are suffering from incurable, far advanced and progressive cancer. An overall treatment strategy not only includes the treatment of physical symptoms but also integrates the psychological, social and spiritual problems of the patients and his/her relatives. The most stressful physical symptom is pain, which may be so severe as to be intolerable. With the judicious use of opioids and adjuvant substances, this can be managed satisfactorily. The opioid of choice is oral morphine. The value of oral oxycodone and hydromorphone has not yet been fully established, and it remains to be seen what role they will play in the future. These two substances are expected to become available in Germany in 1998. 相似文献
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AK Nigam RP Srivastava S Saxena BS Chavan KR Sundaram 《Canadian Metallurgical Quarterly》1994,89(3):317-320
Naloxone-induced withdrawal was studied in seven patients currently dependent only on injecting buprenorphine, within 3 to 6 hours of their last dose. Withdrawal severity began to rise from 5 minutes and reached a peak at 60 minutes after 1.2 mg naloxone given intravenously. The mean withdrawal severity score was significantly higher at 30, 60 and 90 minutes compared to the baseline. The most frequent withdrawal signs and symptoms were mydriasis, systolic hypertension, tachypnoea, muscle pains, yawning, anxiety, restlessness and craving. 相似文献
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1969 Sevofluran was synthesized and in December 1995 licensed for clinical use in Germany. The low blood/gas partition coefficient is responsible for the fast uptake and elimination of sevoflurane. Sevoflurane does not irritate the airway. In human medicine no side effect of liver- and kidney function have been seen after sevofluran anaesthesia. There is low cardiovascular and respiratory depression caused by sevoflurane. In this study the use of sevoflurane in dogs should be tested and compared with isoflurane and halothane anaesthesia. All dogs were premedicated with /-methadon and diazepam. No significant depression of the cardiovascular system was seen. Neither kidney-nor hepatotoxic side effects could be found after sevoflurane, isoflurane and halothane anaesthesia. After sevoflurane anaesthesia the dogs woke up quietly and without any excitation and were able to stand on average ten minutes earlier after sevoflurane anaesthesia than after isoflurane and 85 minutes earlier than after halothane anaesthesia. 相似文献
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CC O''Callaghan 《Canadian Metallurgical Quarterly》1996,13(2):43-49
In 75 patients following ablative surgery of head and neck cancer, reconstruction was attempted with free tissue transfer techniques under magnification. It was possible to do free tissue transfers in 69 cases. In 6 cases it was not possible to harvest free flaps successfully and alternative reconstructive procedure was carried out due to unavoidable circumstances and various reasons: 1. unsuitable venous drainage, as in Anterior Rib Osteomyocutaneous Composite Flap, AROCF (2 cases), 2. injury to vessels during flap harvest, as in parascapular flap (1 case), 3. residual disease unable to excise (2 cases) and 4. unsuitable proposition (1 case), due to emergency curfew imposed suddenly. These 6 cases were not included in the study. Free tissue transfer was successful in 64 cases (92.7%) and there was a total failure in 5 cases where delayed secondary salvage surgery was performed. Out of 69 cases, in 65 cases reconstructions were carried out immediately, primarily as one-stage operative procedure. Their functional, cosmetic results and complications during the operative and post-operative period are analyzed and discussed. Inter-maxillary fixation was never used to maintain the bite alignment. All cases were given a bite guide prosthesis in the early post-operative period, to improve the bite alignment when it was necessary. 相似文献
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The aetiology of idiopathic facial nerve palsy (Bell's palsy) and sudden deafness are not known, although viruses have been suspected as a cause of them. We investigated the relationship between Bell's palsy or sudden deafness, and reactivation of cytomegalovirus, human herpesvirus 6 (HHV-6) and 7 (HHV-7). Paired sera were collected from 22 patients with Bell's palsy and 24 patients with sudden deafness. IgG antibody titres to HHV-7 were increased in one patient with Bell's palsy. IgG antibody titres to HHV-6 were increased in one patient with Bell's palsy and two with sudden deafness. IgG antibody titres to cytomegalovirus were increased in one patient with sudden deafness. Titres of the three viral antibodies were not increased simultaneously in any patients. These viruses may contribute to the development of Bell's palsy or sudden deafness in some cases. It is, however, unlikely that these viruses are the main cause of Bell's palsy and sudden deafness in the majority of patients. 相似文献
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K Taniguchi H Fujiwara T Iizumi A Niwa Y Shintomi 《Canadian Metallurgical Quarterly》1977,41(4):413-4, 429-34
False triggering with a ventricular triggered pacemaker and false inhibition with a ventricular inhibited pacemaker were observed in two patients with complete heart block. These arrhythmias were considered to be attributable to false sensing with a demand pacemaker. Both in vitro and in vivo studies were performed to elucidate the mechanism of these false sensings, and the false sensings were reproduced in a series of experiments. Loose contact of the tip of electrodes to myocardial tissue, refractory period, the distance between two electrodes, and the after potential and its dv/dt of pacemaker impulses are considered to affect the performance of demand pacers. 相似文献
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The implantation process of the Solcograft-P vascular prosthesis in infrarenal aortic and vena cava inferior positions was studied in dogs in the first 100 postoperative days to investigate its applicability in vascular surgery. The intimal lining was consistently smooth and homogeneous, the problems of aneurysma formation was not serious. Infection and early thrombosis were not more frequent than with other grafts. The impregnated Solcograft-P seemed to be superior to its previous version, the Solcograft. The morphological properties of Solcograft-P seem to make it suitable for venous replacement. The experiments suggested that in selected cases of reconstructive vascular surgery and particularly for patch plastics, Solcograft-P may prove useful. 相似文献
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Patients with preterm labor not only suffer from anxiety and uncertainty regarding the healthy development of their child but, especially as inpatients, in part severely from loss of autonomy and feelings of insufficiency. By the creative therapeutic means of art therapy it is aimed at influencing the disturbed emotional state and strengthening self-esteem. During the sessions patients experience challenge, success and relaxation with endurance some time after the sessions. Paintings produced by hospitalized patients in art therapeutic sessions are presented. Further psychophysiological investigations are in process for controlling the effects on preterm labor. Paintings of inpatients are discussed. 相似文献
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The introduction of market forces into health care delivery systems has had a number of important influences on the roles nurses perform. There have been increasing efforts to find alternative and more cost-effective ways of delivering care. One facet of this situation has been the examination of the roles and responsibilities of registered nurses (RNs) with the view of exploring different ways of using professional skills and determining if RN services are always required. One result of this has been the increased use of unlicensed personnel. The substitution of professional nursing staff by unlicensed personnel has become a major concern for practitioner, manager and client alike. This paper reviews some of the concepts of economic substitution as well as the assumptions advanced for the use of unlicensed personnel in clinical areas as a substitute for nursing services. While there has been increased use of unlicensed staff, the evaluation of clinical outcomes has been poor. This paper reviews primarily the hospital-based evidence about the impact of using unlicensed personnel in practice, and suggests there are methodological problems with the research published to date. Findings suggest that substitute service providers generally 'do no harm'. By contrast, evidence is presented indicating the major contributions nurses make to client care when adopting advanced practice roles (acting as a substitute for other professionals). 相似文献
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OBJECTIVE: To evaluate indications for and complications, efficacy, and effects on renal function of unilateral nephrectomy in dogs with renal disease, and to evaluate the role that scintigraphy had in the decision to excise a kidney. DESIGN: Retrospective case series. ANIMALS: 30 dogs with renal disease that underwent unilateral nephrectomy. A comparison group of 12 dogs with renal calculi that underwent renal scintigraphy but not nephrectomy was included. RESULTS: Indications for nephrectomy included renal or ureteral calculi (n = 10), renal mass (8), chronic pyelonephritis (5), perirenal mass (3), severe hydronephrosis and hydroureter (3), and renal hypoplasia with ureteral ectopia (1). None of the dogs were azotemic before surgery. Renal scintigraphy apparently influenced the decision to perform nephrectomy, because in 14 of 16 dogs that underwent nephrectomy, the affected kidney contributed < or = 33% of the total glomerular filtration rate, but in 6 of 8 comparison dogs that underwent nephrotomy, the affected kidney contributed > 33% of total glomerular filtration rate. Complications of nephrectomy included oliguria (5) and organ laceration (2). Mean +/- SD final serum creatinine concentration for 16 dogs alive at least 6 months after nephrectomy was 2.2 +/- 1.8 mg/dl. Three dogs had chronic renal failure of undetermined cause at the time of death. Nephrectomy did not completely resolve the underlying disease in 13 dogs. Renal function was evaluated in 6 dogs 2 to 3.5 years after nephrectomy and was impaired in 4. None of the dogs were anemic, azotemic, proteinuric, or hypertensive. Survival time varied depending on the underlying disease. CLINICAL IMPLICATIONS: Multiple factors contributed to the decision to perform nephrectomy. Unilateral nephrectomy resulted in few serious complications and was not detrimental to the remaining kidney, but did not always resolve the underlying disease. 相似文献