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71.
JA Turpin Y Song JK Inman M Huang A Wallqvist A Maynard DG Covell WG Rice E Appella 《Canadian Metallurgical Quarterly》1999,42(1):67-86
Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in viral replication and their mutationally nonpermissive nature. On the basis of our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194-1197), we synthesized and evaluated variants of these dimers, including sets of 4,4'- and 3,3'-disubstituted diphenyl sulfones and their monomeric benzisothiazolone derivatives (BITA). BITAs generally exhibited diminished antiviral potency when compared to their disulfide precursors. Novel, monomeric structures were created by linking haloalkanoyl groups to the benzamide ring through -NH-C(=O)- (amide) or -S-C(=O)- (thiolester) bridges. Amide-linked compounds generally lacked antiviral activity, while haloalkanoyl thiolesters and non-halogen-bearing analogues frequently exhibited acceptable antiviral potency, thus establishing thiolester benzamides per se as a new anti-HIV chemotype. Pyridinioalkanoyl thiolesters (PATEs) exhibited superior anti-HIV-1 activity with minimal cellular toxicity and appreciable water solubility. PATEs were shown to preferentially target the NCp7 Zn finger when tested against other molecular targets, thus identifying thiolester benzamides, and PATEs in particular, as novel NCp7 Zn finger inhibitors for in vivo studies. 相似文献
72.
The time evolution of the density operator of an AB spin system during a double-spin-echo pulse sequence is evaluated analytically by a computer-algebra system. The computer-algebra system allows one to generate the extensive formulas describing the density operator and yields an expression for the integral of the spectral signals. The simulation of spectra for arbitrary sequence timings can be easily performed by this new tool without risking errors that might occur in conventional calculations. The computer-algebra method can be extended straightforward to other pulse angles and types of sequences. The double-spin-echo pulse sequence is used in the point-resolved spectroscopy (PRESS) method which is often applied for volume selective examinationsin vivo. For verification of the results generated by the computer-algebra system,1H spectra from a half-liter spherical sample with an aqueous solution that was 0.1 M in sodium citrate and 0.1 M in sodium acetate were recorded after 90°-180°-180° double-spin-echo pulse sequences on a 1.5-T whole-body unit. The measured behavior of the citrate AB spin system corresponds very well with the theoretical predictions. Thus, the theory provides the basis for the optimization of sequence timings for double-spin-echo measurements with high signal gain from AB systems as, for example, citrate. In addition, the theoretically predicted signal modulations could be fitted to the experimental data, providing the transverse relaxation time of the AB-coupled protons. 相似文献
73.
Fritz Schick 《Magma (New York, N.Y.)》1993,1(3-4):158-168
Numerically optimized hard pulse sequences were developed providing a frequency selective response of the transverse and longitudinal magnetization for several applicationsin vivo. The sequences are based on pulse trains with binomial ratios of the pulse angles and constant time intervals between the pulses. These pulse trains were systematically optimized to obtain broad Larmor frequency ranges in which the magnetization is not markedly influenced by the pulse sequence. In addition, the sequences had to provide maximum transverse magnetization or complete inversion of the magnetization beside the suppression range. Such behaviour is needed for chemical shift selective imaging, pulsed magnetization transfer, and frequency selective spectroscopyin vivo. The phase of the magnetization response is shown and adequate rephasing conditions are discussed as well as the actual phase duration. Short optimized hard pulse sequences for water and fat-selective imaging provide lowT
2-sensitivity of the resulting magnetization. The new optimized hard pulse sequences are suitable, if optimum suppression of signals at one single point in the Larmor frequency spectrum is less important than good suppression in a larger frequency range. 相似文献
74.
BACKGROUND: Haemangiopericytomas are rare vascular neoplasms which show either slow local tumour growth or aggressive progression in size with a high tendency of recurrence and metastasis. Manifestations of haemangiopericytomas in the area of the nose and sinuses are supposed to have a relatively benign course. To date clinical and histological parameters for prognosis are uncertain. Therefore in a quite large number of cases only the clinical course allows to evaluate the dignity of a haemangiopericytoma. PATIENTS AND RESULTS: We present our experience with five haemanglopericytomas in contact with the skull base out of a total number of 457 skull base tumours. The site of origin of these five haemangiopericytomas were: nasal septum, pterygopalatine fossa, oronasopharynx, temporal bone, and parotid gland. All neoplasms showed primary or recurrent tumor in contact with the skull base and an intracranial extension was observed twice. One patient died postoperatively of a cerebral infarction. Three patients showed one or more recurrences which were treated surgically. In one case 5 recurrences occurred. Despite of 4 surgical procedures within a period of 15 months, the tumour could be controlled only for a short period of time, and the patient died 16 months after the first operation. CONCLUSION: One has to consider that haemangiopericytomas of the head and neck show a potential malignant course. The vascular tumor may recur decades later. Adequate therapy and life-long follow-up are therefore mandatory in haemangiopericytomas. Complete surgical resection of the tumour is usually the treatment of choice, in spite of the high degree of surgical skill required, especially in advanced tumour and in case of recurrence. 相似文献
75.
ML Loh TW McLean JD Buckley W Howells DG Gilliland FO Smith 《Canadian Metallurgical Quarterly》1998,22(5):461-464
The percutaneous cardiopulmonary support system (PCPS) was used in a 64-year-old woman with cardiogenic shock due to sustained ventricular fibrillation (Vf) caused by severe aortic stenosis and regurgitation. The Vf attack was resistant to cardioversion and adrenaline for lack of left ventricular support by PCPS. She was transported to the operation theater with PCPS in situ and emergency aortic valve replacement was performed. Although preoperative cardiac resuscitation time was long (35 minutes), she was discharged from the hospital on foot without any neurological complications on 84th postoperative day. Because PCPS does not decrease left ventricular systolic stress in poorly contracting dilated heart, early surgical treatment is needed in patients with severely damaged heart. 相似文献
76.
77.
We examined whether timeline icons improved older and younger adults' comprehension of medication information. In Experiment 1, comprehension of instructions with the icon (icon/text format) and without the icon (text-only format) was assessed by questions about information that was (a) implicit in the text but depicted explicitly by the icon (total dose in a 24 hour period), (b) stated and depicted in the icon/text condition (medication dose and times), and (c) stated but not depicted by the icon (e.g., side effects). In a separate task, participants also recalled medication instructions (with or without the icon) after a study period. We found that questions about dose and time information were answered more quickly and accurately when the icon was present in the instructions. Notably, icon benefits were greater for information that was implicit rather than stated in the text. This finding suggests that icons can improve older and younger adults' comprehension by reducing the need to draw some inferences. The icon also reduced effective study time (study time per item recalled). In Experiment 2, icon benefits did not occur for a less integrated version of the timeline icon that, like the text, required participants to integrate dose and time information in order to identify the total daily dose. The integrated version of the icon again improved comprehension, as in Experiment 1, as well as drawing inferences from memory. These findings show that integrated timeline icons improved comprehension primarily by aiding the integration of dose and time information. These findings are discussed in terms of a situation model approach to comprehension. 相似文献
78.
Our objective was to examine the influence of feeding and endogenous GH secretion on circulating IGF-I in colostrum-deprived newborn pigs fed colostrum (n = 4), formula (control, n = 4), or water (n = 4). In another four formula-fed pigs, GH was ablated (GRF-A) with two intravenous injections of a GH releasing-factor antagonist (N-Ac-Tyr1,D-Arg2)-GRF(1-29)-NH2. Blood was serially sampled in all pigs to measure plasma IGF-I and GH profiles. Feeding increased plasma IGF-I concentration two- to fourfold and decreased GH secretion. Despite a more than 80% decrease in the plasma GH in GRF-A pigs, the circulating IGF-I concentration was similar to that in control pigs. In colostrum-fed pigs, plasma IGF-I was higher than that in control pigs, despite equal nutrient intake and lower circulating GH. There were no differences in plasma IGF binding protein (IGFBP)-3 levels among the treatment groups. However, the relative abundance of plasma IGFBP-4 was lower, and that of IGFBP-1 higher, in unfed pigs than in any of the three fed groups. The plasma insulin concentration was not different among fed pigs, but it was lower in unfed pigs. Our results indicate that the circulating IGF-I concentration is more dependent on nutrient intake than on GH in newborn pigs, despite relatively high GH concentrations. However, because the nutrient content in the formula was designed to match that of colostrum, a factor other than nutrient intake and GH was responsible for the maximal increase in circulating IGF-I concentration observed in colostrum-fed pigs. 相似文献
79.
E Galanis JC Buckner BW Scheithauer DW Kimmel PJ Schomberg DG Piepgras 《Canadian Metallurgical Quarterly》1998,82(10):1915-1920
BACKGROUND: Meningeal hemangiopericytoma is an uncommon neoplasm with a high propensity for recurrence. The purpose of this study was to analyze the efficacy of different treatment options in patients with recurrent disease. METHODS: The records of all patients with recurrent meningeal hemangiopericytoma treated at the study institution between 1976 and 1996 were reviewed. RESULTS: Thirty-four consecutive patients were studied. The mainstay of treatment was brain surgery in 21 patients (62%); the median time to recurrence from surgery was 12 months. Ten patients (29%) had 20 recurrent central nervous system (CNS) lesions treated by stereotactic radiosurgery. Of these, 3 previously nonirradiated patients (all with lesion size < 25 mm) achieved a complete response, which persisted at a median of 3 years. In 14 lesions (70%) a partial response (PR) occurred with a median duration of 12 months, whereas 3 lesions (15%) remained stable. Two patients with inoperable CNS lesions received external beam radiation therapy and both had PRs lasting 14 and 24 months, respectively. Nine patients (26%) received radiation therapy for metastatic disease. Of these, seven patients remained stable with good symptomatic relief, and two patients experienced tumor progression. Chemotherapy with doxorubicin-containing regimens was administered in 7 patients (21%); there was only 1 PR that lasted 8 months. The median survival from first recurrence was 4.6 years. CONCLUSIONS: Surgical management is important for the successful treatment of patients with recurrent meningeal hemangiopericytoma. Radiosurgery plays a definite role in the treatment of smaller recurrent CNS lesions. Radiation therapy is helpful in the management of inoperable tumors. More effective chemotherapeutic agents are needed. 相似文献