Optimization of epitope processing enhances immunogenicity of multiepitope DNA vaccines

Experimental DNA vaccines comprised of multiple minimal cytotoxic T lymphocytes (CTL) epitopes can effectively induce broad CTL responses; however, such constructs frequently exhibit significant variation in epitope immunogenicity. Antigenicity assays utilizing human cells transfected with one such multiepitope construct revealed that the epitopes with poor immunogenicity were inefficiently processed in transfected cells. Compilation of a database of 94 epitope/flanking region combinations, for which immunogenicity was measured experimentally, revealed that the type of residue immediately following the carboxyl-terminus of the epitope exerted a prominent effect on immunogenicity. Experiments utilizing a variety of HBV-specific vaccine constructs demonstrated epitope immunogenicity could be modulated by the insertion of a single amino acid and the effect on immunogenicity could be ascribed to modulation of processing efficiency. These findings demonstrate that multiepitope DNA vaccines can be engineered to enhance CTL immunogenicity by increasing processing efficiency.     

Students'' expectations of postregistration degree programmes

The needs of postregistration students pursuing degree-linked clinical courses have received little attention and there are few insights concerning their aspirations when they enrol on such courses. Thus the aim of this study was to explore postregistration students' perceptions of the specific needs of their patient/client group and to examine how they envisaged the course on which they had just enrolled might help them to meet these needs in addition to their own requirements for professional and personal development. Data were collected by group interview from 62 students enrolling on eight different postregistration courses, all employed in an acute hospital trust. The results were analysed inductively. They indicated that students had internalized the state of the healthcare market and were keenly aware of the need to fulfil the expectations of employers and the public, while fulfilling their own needs for education and pursuing their own professional and career trajectories. They appeared ambitious and yet appeared to demonstrate empathy for patients and their families and felt a tremendous desire to provide care of a high quality through the optimal development of technical expertise. Students' emphasis on the importance of keeping abreast of technological developments should not be lightly dismissed considering its prominent position within the acute areas where they were employed, especially as it did not replace their desire to promote the caring aspects of their work.     

新缩瞳剂包公藤甲素人工合成研究

包公藤甲素是从包公藤(Erycibe obtusifolia Benth.)茎中提得的一个新莨菪烷生物碱,具有强烈的缩瞳作用,临床用于治疗青光眼。本文报道用合成的6β-乙酰氧基托品酮为原料,经卤代、水解、还原和N-去甲基化等反应合成包甲素(8)。经光谱测定证实8与天然包甲素的结构完全一致。合成品系外消旋体,其作用机理与天然品相同,而强度则减半。     

Osteosarcoma: use of MR imaging and MR spectroscopy in clinical decision making

Magnetic resonance (MR) imaging was performed on 14 patients with histologically proved osteosarcoma (mean age, 14.4 years). There was excellent correlation of intramedullary tumor extent as determined with MR imaging and pathologic examination (r = 99%). This was facilitated by the presence of a chemical shift artifact at the tumor-marrow interface on the T1-weighted images. The correlation between CT and pathologic findings was not as good (r = 84%). In a single patient, however, a 10-cm length of sclerotic bone was incorrectly interpreted as being tumor. If this case is excluded, the correlation between CT and pathologic findings improves significantly (r = 96%). T2-weighted images were optimal in demonstrating soft-tissue bulk and breach of the epiphysis or cortex. Vascular involvement was also readily defined. The T2 value of the tumor soft-tissue component decreased in patients who were deemed to have responded well to therapy. Two patients with very high T2 values after chemotherapy developed wide-spread metastatic disease and died. Phosphorus-31 MR spectroscopy of five patients with osteosarcoma showed elevated levels of phosphomonoesters (PMEs), inorganic phosphate (Pi), and phosphodiesters (PDEs). PME and PDE peak areas decreased in three patients after chemotherapy, while Pi peak areas increased.     

Primary Ewing sarcoma: follow-up with Ga-67 scintigraphy

While avid accumulation of gallium-67 citrate and technetium-99m methylene diphosphonate (MDP) occurs initially in most cases of primary Ewing sarcoma, uptake after therapy is less well defined. Thirty patients with Ewing sarcoma who underwent Ga-67 and bone scintigraphy at diagnosis, at completion of therapy, and at relapse from 1978 to 1988 were evaluated. All 30 patients showed less primary site Ga-67 activity following therapy. Twenty-three of 28 patients who underwent corresponding bone scintigraphy showed less uptake, but residual activity was usually more intense than with Ga-67. Avid reaccumulation of Ga-67 occurred in four of five patients with primary site relapse, while patients who underwent bone scintigraphy showed less change. It was concluded that a greater decrease in Ga-67 than in Tc-99m MDP uptake often occurs in patients successfully treated for primary Ewing sarcoma. Information obtained at Ga-67 scintigraphy is most likely to be helpful if results of bone scintigraphy remain abnormal or if occult relapse is suspected.     

Late asthmatic reaction to perennial and seasonal allergens.

Twelve patients with asthma sensitized to Dermatophagoides pteronyssinus and Parietaria judaica were studied. Patients were challenged before (winter), during (summer), and after (autumn) Parietaria-pollen season. Early asthmatic reaction was positive for both allergens, and the provocative dose causing a 15% decrease of FEV1 was similar in all seasons. The provocative dose of methacholine causing a 15% decrease of FEV1 and specific IgEs for both allergens were also not significantly different throughout the time of study. Late asthmatic reaction (LAR) to Dermatophagoides occurred in eight of 12 patients in winter, in six of nine in summer, and in five of six patients in autumn. The severity of LAR, expressed as the maximum fall of FEV1 3 to 8 hours after challenge, was not significantly different between seasons. LAR to Parietaria occurred in only one of 12 patients in winter, in six of 11 in summer, and in one of six patients in autumn. In summer, LAR to Parietaria was significantly more severe than in winter. In both winter and autumn, but not in summer, LAR to Dermatophagoides was significantly more severe than to Parietaria. We conclude that LAR is allergen specific, and natural exposure has a priming effect on LAR.     

Nurses'' opinions of the introduction of computer-assisted learning for use in patient education

Computers have only recently begun to find a place in the everyday work of health care staff. The use of computer-assisted learning (CAL) in patient education is in its infancy. However, the medium appears to offer several advantages to patients. The successful integration of the medium into clinical practice requires the acceptance and support of staff members. Little research exists to date which examines staff responses to the introduction of CAL into their workplace. This small study (n = 14) aims to explore the reactions of staff to the introduction of an experimental CAL package for use in the education of renal patients on continuous ambulatory peritoneal dialysis (CAPD). The opinions of staff members to CAL are probed and their views ascertained regarding the usefulness of CAL to both staff and patients. Results suggest that, despite their initial reservations about CAL, staff were generally positive about the medium.     

Surface of the brain: three-dimensional MR images created with volume rendering

Image processing and volume rendering have been applied to magnetic resonance (MR) images to produce three-dimensional views of the surface of the brain. Four healthy volunteers and 17 patients with a variety of disorders underwent MR imaging of the head, and these images were processed and subjected to volume rendering. The resulting three-dimensional views depict abnormalities of the brain surface, as well as important landmarks of normal brain surface anatomy such as precentral, postcentral, superior temporal, and inferior frontal gyri, which are difficult to identify on cross-sectional images.