Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes

A number of cytolytic T lymphocyte (CTL) clones derived from several melanoma patients have been found to recognize a majority of melanomas from HLA-A2 patients. We have reported previously that two such CTL clones recognize a product of the tyrosinase gene that is presented by HLA-A2. Here we show that one of these CTL clones recognizes a peptide encoded by the first nine amino acids of the putative signal sequence of tyrosinase. The other CTL clone recognizes a different tyrosinase peptide corresponding to amino acids 368–376. Both peptides contain consensus motifs of HLA-A2 binding peptides.     

Computerized diagnosis: implications for clinical education

The advent of the small computer as a basic clinical tool will have a significant impact on clinical practice and medical training. The application of probability theory to clinical diagnosis has led to the development of several practical diagnostic programs which run on small computers. Expert systems--interactive programs which function as 'electronic consultants'--have now been successfully developed for a number of clinical situations. Experience with two of these, INTERNIST/CADUCEUS and MYCIN, has provided insight into problems and prospects for expert systems in medicine. Less complex programs, particularly those employing clinical prediction rules, and expert system shells, seem well suited for clinical environments. Although computerized medical diagnosis holds great promise as an aid to clinicians, its success will largely be determined by the quality of the information that clinicians provide for analysis. A brief review of the status of bedside diagnosis reveals that data-gathering strategies and techniques must be better understood. In order to take full advantage of computer programs for diagnosis, basic diagnostic skills must be more heavily emphasized in clinical training.     

The workload of trainees in general practice

During their first training period in general practice the authors felt that they did not encounter the balanced workload which is the foundation for learning to be a GP. Previous studies confirmed the existence of differences in overall and specific workload between trainees and trainers. From their own experience and from the relevant literature they addressed several factors which might affect the workload of trainees. A study was undertaken to determine differences in workload between trainees and trainers, and to investigate whether certain characteristics of practice and of trainees affect the workload of trainees. Details of surgery consultations with 34 trainee-trainer partnerships were recorded in the north of the Netherlands over 2 weeks. Questionnaires were filled in by trainers, trainees and practice assistants from these 34 general practices. The total number of contacts recorded was 10,103. It was found that trainees see fewer elderly and female patients, less chronic and oncological conditions, but more minor illnesses. They see only 30% of patients with problem behaviour. Factors that influence the trainees' workload, as compared to their trainers' are: list size; selection in the allocation of patients; trainee's experience prior to starting the training stage, and the trainee's sex. Except for problem behaviour, trainees generally see a cross-section of their trainer's practice population. Selection would provide a more balanced workload for trainees.     

Basic sciences in problem-based learning and conventional curricula: students' attitudes

The purpose of this study was to compare the attitudes toward basic sciences of students in a preclinical problem-based curriculum and a conventional lecture-based curriculum at the end of their second year of medical school. The results showed that the PBL class had more positive attitudes toward basic sciences than students in the conventional class. These results may reflect a learning environment where students meet many scientist role models as teachers and where basic science is learnt in the context of clinical problems.     

Factors determining the performance of medical students of the Faculty of Medicine, University of Kuwait

An investigation was undertaken to determine the factors influencing performance of medical students at the Faculty of Medicine, University of Kuwait. Data were collected for the first batch of 42 candidates who successfully passed the 7-year medical programme. Results showed high correlations between high-school admission grades and subsequent performance during the medical programme. Similar results were also obtained with English proficiency. A partial correlation controlling for English proficiency, however, showed a systematic decline in the magnitude of the correlations between high-school grades and performance during the medical programme. In fact the relationship between high-school GPA and clinical GPA was non-significant. A prominent influence of English proficiency on performance is indicated.     

A questionnaire examining learning in general practice

Vocational training is a key element of professional development in general practice. Learner-centred approaches to teaching bring a need for greater understanding of the individual learning styles and preferences of trainees. This paper reports the findings of a pilot study undertaken to determine factors that may influence learning among general practice trainees. A questionnaire survey of 261 trainees in six regions in the UK was carried out to explore attitudes to a series of themes identified in semi-structured interviews with trainees at the end of their training. Six distinct subscales were identified using principal components analysis. These are named 'Learning from Patients', 'Openness to Criticism', 'Negative Attitudes', 'Desire for Clear Guidelines', 'Peer Support', and 'Academic Approach'. Males scored significantly higher on 'Academic Approach' (   P < 0.05  ). Each of the subscales reflects themes that permeate the atmosphere of general pratice training. Further work is required to establish relationships between the subscales and the outcomes of learning and to explore the implications for continuing professional development. The questionnaire is an instrument that may prove useful in the future investigation of learning in general practice.     

HLA-A9 antibodies and epitopes

Fifty pregnancy alloantisera directed towards HLA-A23 and/or A24 antigens were investigated serologically in titration studies against the three sequenced HLA-A9 specificities, A23 (A*2301), A24 (A*2402) and A2403 (A*2403). The reaction patterns of the antisera fell into five categories which allowed the three HLA-A9 specificities to be easily differentiated. Based on the various titre cytotoxicity scores of the antisera five possible antibody specificities were defined: anti-A23; -A24; -A23/24; -A24/2403 and anti-A23/24/2403. One antiserum crossreacted with HLA-A1 and A24. Inspection of the amino acid sequences of 136 HLA-A, B and C molecules allowed the prediction of five unique epitopes corresponding to these antibody specificities, a possible epitope unique to A2403 and confirmation of a likely epitope shared by A1 and A24. These, together with the previously suggested epitopes HLA-A9/ A2/A28 and A1/A23/A24 together with the presence of Bw4 on the three HLA-A9 antigens suggests that the HLA-A9 family of antigens is characterized by a minimum of nine serologically definable epitopes.     

Identification of a novel gp100/pMel17 peptide presented by HLA-A*6801 and recognized on human melanoma by cytolytic T cell clones

Melanoma-associated peptides recognized by cytolytic T lymphocytes (CTL) in the context of several histocompatibility leukocyte antigens (HLA) are required for the development of specific immunotherapies. Using a transient transfection assay into COS-7 cells, we identified the gp100/pMel17 melanosomal protein as the shared antigen recognized by three independent CD8+ CTL clones in HLA-A*6801-restricted fashion. This finding was confirmed by the correlation between lack of gp100/pMel17 protein in a number of HLA-A*6801-positive melanomas and their resistance to lysis/cytokine production by the specific effectors. The gp100/pMel17 antigenic epitope was identified based on recognition of subfragments and on a computer-based prediction algorithm. Among a panel of gp100/pMel17-derived synthetic peptides only the 10-mer HTMEVTVYHR (gp100/pMel17182-191) induced tumor necrosis factor (TNF) release by CTL clones when pulsed on suitable target cells whereas both the 10-mer and the shorter 9-mer gp100/pMel17183-191 sensitized the same antigen-pulsed cells to lysis. In conclusion, the identification of the HTMEVTVYHR peptide will extend to HLA-A*6801 melanoma patients the possibility to exploit gp100/pMel17 melanosomal protein for experimental and clinical studies.     

新等位基因人类白细胞抗原B*4609的发现和确认

目的 鉴定一个人类白细胞抗原(human leukocyte antigen,HLA)新等位基因HLA-B*4609.方法 使用序列特异性寡核苷酸PCR技术进行HLA基因分型,发现反应格局异常的可疑新等位基因,应用分子克隆和DNA双向测序技术测定新等位基因的核苷酸序列,并与已知等位基因进行序列比对分析.结果 检出1个样本HLA-B位点反应格局异常,DNA测序分型结果一个为B*151101,另一个的核苷酸序列与已知的HLA等位基因均不同,该基因序列与同源性最高的HLA-B*460101基因序列相比,在第3外显子区域中527位碱基发生A→T突变,导致176位编码氨基酸由谷氨酸(GAG)变成缬氨酸(GTG).结论 样本中含有HLA-B新等位基因序列.该序列申报后,被世界卫生组织HLA因子命名委员会正式命名为HLA-B*4609.     

Characterization of a novel HLA-DQB1 allele, DQB1*020102

A novel human leukocyte antigen (HLA)-DQB1 allele, DQB1*020102, was detected in a 28-year-old woman of Han ethnic in Guangzhou, China. Compared with HLA-DQB1*020101 and HLA-DQB1*0202, they differed in only one nucleotide at the position 167 (C to T) of exon 2, which was a highly conserved position. This is a synonymous mutation, which does not cause any change in the amino acid sequence of mature protein.