CTLA4 mediates antigen-specific apoptosis of human T cells

The regulation of T cell-mediated immune responses requires a balance between amplification and generation of effector function and subsequent selective termination by clonal deletion. Although apoptosis of previously activated T cells can be induced by signaling of the tumor necrosis factor receptor family, these molecules do not appear to regulate T-cell clonal deletion in an antigen-specific fashion. We demonstrate that cross-linking of the inducible T-cell surface molecule CTLA4 can mediate apoptosis of previously activated human T lymphocytes. This function appears to be antigen-restricted, since a concomitant signal T-cell receptor signal is required. Regulation of this pathway may provide a novel therapeutic strategy to delete antigen-specific activated T cells.     

Aggression and the psychic self

In this paper we explore the idea of aggression as a defence against threats to the psychological self. This aspect of the self allows reflection about people in psychological terms and develops, in the first three years of life, through appreciation of mental states in the other. When the object is unpredictable or hostile, recognition of this is painful to the child, and his reflective function will not be adequately established. The defences of aggression or avoidance will be invoked very frequently. In time, aggression may become an organising influence in the construction of the self; pathological destructiveness then takes the place of emotional relatedness and concern for the other. Psychoanalytic treatment no longer works primarily by addressing conflict. Instead, particularly through interpretations of transference and countertransference, the analyst recreates an intersubjective process which enhances the patient's reflective self, this time in the safety of a benign relationship.     

Systemic lupus erythematosus in three ethnic groups: II. Features predictive of disease activity early in its course. LUMINA Study Group. Lupus in minority populations, nature versus nurture

OBJECTIVE: To determine the factors associated with disease activity in patients with recent-onset (< or =5 years) systemic lupus erythematosus (SLE) who were of Hispanic, African-American, or Caucasian ethnicity. METHODS: Incident and prevalent cases of SLE, as defined by the American College of Rheumatology criteria for SLE, among the 3 ethnic groups were identified in Alabama (The University of Alabama at Birmingham) and Texas (The University of Texas-Houston Health Science Center and The University of Texas Medical Branch at Galveston). Variables from the sociodemographic, clinical, immunologic, immunogenetic, behavioral, and psychological domains were obtained using validated instruments. Disease activity was ascertained with the Systemic Lupus Activity Measure (SLAM). Stepwise domain regressions with SLAM score as the dependent variable were performed. Final ethnic-specific and overall regression models were obtained by entering variables that were retained in the domain regressions. RESULTS: SLAM scores at study entry were higher in the African Americans (mean +/- SD 12.6 +/- 6.9) and Hispanics (11.0 +/- 6.2) than in the Caucasians (8.5 +/- 3.7) (P < or = 0.001). The final overall regression model (R2 = 28%) for higher SLAM score included the following variables: African-American ethnicity, lack of private health insurance, abrupt disease onset, presence of anti-Ro antibodies, absence of HLA-DRB1*0301, higher levels of helplessness, and abnormal illness-related behaviors. CONCLUSION: Socioeconomic, immunologic, immunogenetic, behavioral, and psychological variables were all predictive of disease activity early in the course of SLE, irrespective of ethnic group. However, there remain ethnic group differences in disease activity that were not explained by these factors.     

The safer choices project: methodological issues in school-based health promotion intervention research

Randomized trials of school-based health promotion programs present unique design and analytical issues not widely discussed in the research literature. This article describes the Safer Choices study--a school-based program for prevention of HIV, other sexually transmitted diseases, and pregnancy--to illustrate critical methodological issues involved in large-scale, school-based intervention trials, particularly those evaluating interventions with a school-wide focus. The issues presented are: 1) comparability of the intervention and control groups even when few units are randomized; 2) factors that affect the decision to use a cohort or cross-sectional design; and 3) appropriate analysis strategy when the unit of randomization and intervention is at the school level, but observations are at the student level.     

超声CO激光的现状和展望(续)

介绍了200kWCW超声电子束连续CO激光器（SSCO－EIL）开环实物模型的能量和光谱特征的实验研究结果，以及增加SSCO－EIL的输出功率，谱线选择性，Q－开关激光作用的数字计算结果，同时讨论了SSCO－EIL的特性对几种激光技术效率的影响，由于激光能量利用率的增加和能量成本的降低，SSCO－EIL拥有的无与伦比的能量和特有的特征，将大大拓宽激光技术的应用领域。     

Technology transfer in digital mammography. Report of the Joint National Cancer Institute-National Aeronautics and Space Administration workshop of May 19-20, 1993

Digital mammography is one of the most promising novel technologies for further improvement of early detection of breast cancer, offering important potential advantages: 1) improved image quality; 2) digital image processing for improved lesion contrast; 3) computer-aided diagnosis for enhanced radiologic interpretation; and 4) teleradiology for facilitated radiologic consultation. The Diagnostic Imaging Research Branch of the National Cancer Institute (NCI) recently funded an international, multidisciplinary, multi-institutional Digital Mammography Development Group for collaborations between NCI, the academic community, and industry to facilitate the integrated development and implementation of digital mammographic systems. Currently, however, digital mammography faces a number of fundamental technological roadblocks: 1) cost-effective digital detectors and displays for imaging systems; 2) the need for novel algorithms for image processing and computer-aided diagnosis; and 3) high performance, low cost digital networks to provide an "information superhighway" for teleradiology. To solve some of these technological problems, the Diagnostic Imaging Research Branch of NCI joined efforts with the Technology Transfer Division of the National Aeronautics and Space Administration to pursue a federal technology transfer program in digital mammography. The authors discuss the findings and recommendations of the workshop entitled "Technology Transfer in Digital Mammography," which was organized and held jointly by the NCI and the National Aeronautics and Space Administration in May, 1993. Numerous innovative technologies of varying degree of promise for digital mammography were presented at the conference. In this article, specific technologies presented at the workshop by the federal and federally-supported laboratories are described, and critiques of these technologies by the leaders of the medical imaging community are presented.     

Neurorehabilitation/geriatric rehabilitation--goals achieved and aims from the viewpoint of the so-called "Vorarlberg Model"

Together with building up a first neurological department in one of the Austrian states we could introduce and organize the 1st scientific institute in literature for neuro-rehabilitation and -prophylaxis. 80% of the neuro-rehabilitation-patients are geriatrics. Hence overlapping of neuro-rehabilitation with rehabilitation in old age is to be postulated. "Rehabilitation of old age groups" as well has been named by us for the 1st time in scientific literature. Moreover we operate such activities on a large scale within a practical and social medical context. As worldover (at least within the civilized countries of high standards) the problem of old age groups is a steadily increasing and important, we are working on a very important scientific sector. Our slogan: "Holistic and permanent" is practically operated as follows: 1. Fluent transition of rehabilitation-adequate acute treatment towards a systematic specialized rehabilitation. 2. Schooling of relatives and follow up rehabilitation service. 3. Introducing rehabilitative thoughts as well in university, teaching as (by separate schoolings) within medical profession and all the other health professions. 4. We emphasize a plurality of methods; to be named here as main examples: integrated physiotherapy as well as integrated psychotherapy. Emphasizing more scientific values for (high age-)rehabilitation, we emphasize as well that it must not be banned into "high age ghettos". Contrarely rehabilitation adapted thinking must be integrated within all the health professions. 5. Innovation, phantasy and pleasure must be introduced into our work. We report of work with lay-groups, animal-visits, hippo-therapy, music, etc. This forms a large interesting territory for an upraising young generation in health professions.     

Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes

Characterization of cytolytic T lymphocyte (CTL) responses to tumor antigens has been impeded by a lack of direct assays of CTL activity. We have synthesized reagents ("tetramers") that specifically stain CTLs recognizing melanoma antigens. Tetramer staining of tumor-infiltrated lymph nodes ex vivo revealed high frequencies of tumor-specific CTLs which were antigen-experienced by surface phenotype. In vitro culture of lymph node cells with cytokines resulted in very large expansions of tumor-specific CTLs that were dependent on the presence of tumor cells in the lymph nodes. Tetramer-guided sorting by flow cytometer allowed isolation of melanoma-specific CTLs and confirmation of their specificity and their ability to lyse autologous tumor cells. Our results demonstrate the value of these novel reagents for monitoring tumor-specific CTL responses and for generating CTLs for adoptive immunotherapy. These data also indicate that strong CTL responses to melanoma often occur in vivo, and that the reactive CTLs have substantial proliferative and tumoricidal potential.     

HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis

OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.