At a scientific meeting in 1968, Jacques Miller was accused of complicating immunology. He and others suggested that there was not one but two kinds of lymphocytes--one from the thymus and one from the bone marrow. In a pair of groundbreaking articles published in the Journal of Experimental Medicine in 1968, Miller and his student Graham Mitchell proved that two subsets of lymphocytes did exist and identified which subset mediated antibody responses. (+info)
Movies, measurement, and modeling: the three Ms of mechanistic immunology.
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Immunological phenomena that were once deduced from genetic, biochemical, and in situ approaches are now being witnessed in living color, in three dimensions, and in real time. The information in time-lapse imaging can provide valuable mechanistic insight into a host of processes, from cell migration to signal transduction. What we need now are methods to quantitate these new visual data and to exploit computational resources and statistical mechanical methods to develop mechanistic models. (+info)
Alan Frederick Williams 25 May 1945 - 9 April 1992.
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Alan WIlliams is noted for his seminal contributions to the field of leucocyte membrane glycoproteins (that is, differentiation antigens). He played a leading role in the development of approaches to the purification and structural analysis of cell surface antigens. His comprehensive characterization of the structure of the rat Thy-1 antigen, as well as the application of monoclonal antibodies to the designation and subsequent isolation of multiple new leucocyte antigens, were exemplary. His discovery that Thy-1 is structurally related to immunoglobulin led directly to the concept of the immunoglobulin (Ig) superfamily, which embraced a spectrum of cell surface molecules involved in a variety of cell recognition systems. He was a very strong advocate in support of the rat as a model animal in the study of immunological phenomena. He was energetic and courageous, as well as radiating enthusiasm for immunological research, inspiring others, critically analysing accepted dogmas and setting high standards. In short, he was a brilliant research scientist. (+info)
The impact of allergy and pulmonary specialist care on emergency asthma utilization in a large managed care organization.
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OBJECTIVE: To evaluate the longitudinal impact of asthma specialist care on the risk of emergency department (ED) visits and hospitalization for asthma. DATA SOURCES/STUDY SETTING: A prospective cohort study using both telephone survey and computerized utilization data. STUDY DESIGN: We recruited a prospective cohort of 4,742 adult members of a closed panel managed care organization who were hospitalized for asthma (the "baseline hospitalization"). DATA COLLECTION/EXTRACTION METHODS: Visits to asthma specialists were ascertained from computerized utilization databases. Specialist visits after baseline hospitalization were defined as time-dependent covariates. An alternative analysis defined specialist visits during the year preceding baseline hospitalization. A subcohort of 596 subjects completed telephone interviews. PRINCIPAL FINDINGS: Compared with subjects who received no specialist visits after baseline hospitalization, treatment by allergists (hazard ratio (HR) 1.04; 95 percent confidence interval (CI) 0.87-1.26) or pulmonologists (HR 0.92; 95 percent CI 0.71-1.19) was not associated with a reduction in the risk of future ED visits for asthma in the entire cohort, controlling for age, sex, race, recent asthma medication dispensing, and pharmacy benefits status. There was also no association between allergist visits and the risk of subsequent hospitalizations for asthma (HR 0.93; 95 percent CI 0.75-1.14). In contrast, visits to pulmonologists (HR 0.74; 95 percent CI 0.55-0.99) were related to a reduced risk of rehospitalization. CONCLUSIONS: Pulmonary specialist visits appeared to reduce the risk of hospitalization for asthma, whereas asthma specialist visits did not reduce the risk of ED visits. In the context of comprehensive prepaid health care, the benefit of specialist care was modest. (+info)
A system for precise analysis of transcription-regulating elements of immunoglobulin genes.
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BACKGROUND: Precise analysis of expression-regulating elements, such as enhancers and insulators, requires that they be tested under reproducible, isogenic conditions. The commonly used methods of transfecting DNA into cell lines and selecting for drug resistance lack the requisite precision, as they yield cell lines in which varying numbers of gene copies have inserted at varying and undefined sites. By contrast, recombination-mediated cassette exchange (RMCE), by which a site-specific recombinase is used to place a single copy of a transgene at a constant chromosomal site of a cell line, offers the necessary precision. Although RMCE is generally applicable, many regulatory elements of interest are tissue-specific in their function and so require cell lines in the appropriate ontogenetic state. RESULTS: As reported here, we have used RMCE in a mouse B hybridoma cell line to establish a system with several additional advantages. To avoid the non-physiological features of prokaryotic DNA, this system uses the immunoglobulin mu heavy chain (IgH) gene from the hybridoma as the reporter. Expression can be measured simply by bulk culture assays (ELISA, Northern blot) and single cell assays (flow cytometry). Expression of the IgH reporter gene varies only 1.5 fold among independent transfectants, and expression is greatly (> 50 fold) increased by inclusion of the IgH intronic enhancer. CONCLUSION: This system is suitable for precise analysis of the regulatory elements of the immunoglobulin loci. (+info)
The human leucocyte differentiation antigens (HLDA) workshops: the evolving role of antibodies in research, diagnosis and therapy.
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The 8th International Workshop on Human Leucocyte Differentiation Antigens (chaired by Zola H and managed by Swart B) was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8th Workshop. We consider what remains to be achieved (including an estimate of the number of leucocyte surface molecules still to be discovered), and how the field can best move forward. (+info)
Macrophage activation unveiled.
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In the early 1960s, George Mackaness showed that macrophages from mice infected with intracellular bacteria could launch an indiscriminate attack against unrelated bacteria. Thus began an explosion of research on the biology of what Mackaness first termed "macrophage activation." (+info)
Application of a static fluorescence-based cytometer (the CellScan) in basic cytometric studies, clinical pharmacology, oncology and clinical immunology.
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The CellScan apparatus is a laser scanning cytometer enabling repetitive fluorescence intensity (FI) and polarization (FP) measurements in living cells, as a means of monitoring lymphocyte activation. The CellScan may serve as a tool for diagnosis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) as well as other autoimmune diseases by monitoring FP changes in peripheral blood lymphocytes (PBLs) following exposure to autoantigenic stimuli. Changes in FI and FP in atherosclerotic patients' PBLs following exposure to various stimuli have established the role of the immune system in atherosclerotic disease. The CellScan has been evaluated as a diagnostic tool for drug-allergy, based on FP reduction in PBLs following incubation with allergenic drugs. FI and FP changes in cancer cells have been found to be well correlated with the cytotoxic effect of anti-neoplastic drugs. In conclusion, the CellScan has a variety of applications in cell biology, immunology, cancer research and clinical pharmacology. (+info)