SIGN-R1, a novel C-type lectin expressed by marginal zone macrophages in spleen,mediates uptake of the polysaccharide dextran

The marginal zone macrophages of the spleen are implicated in the clearance of polysaccharides, but underlying mechanisms need to be pinpointed. SIGN-R1 is one of five recently identified mouse genes that are homologous to human DC-SIGN and encode a single, external, C-terminal C-type lectin domain. We find that a polyclonal antibody to a specific SIGN-R1 peptide reacts primarily and strongly with a subset of macrophages in the marginal zone of spleen and lymph node medulla. In both sites, SIGN-R1 exists primarily in an aggregated form, resistant to dissociation into monomers upon boiling in SDS under reducing conditions. Upon transfection into three different cell lines, high-mol.-wt forms bearing SIGN-R1 are expressed, as well as reactivity with ER-TR9, a mAb previously described to react selectively with marginal zone macrophages. SIGN-R1-expressing macrophages preferentially sequester dextrans following i.v. injection. Likewise, when phagocytic cells are enriched from spleen and tested in culture, dextran is selectively endocytosed by a subset of very large SIGN-R1(+) cells representing approximately 5% of total released macrophages. Uptake of FITC-dextran by these macrophages in vivo and in vitro is blocked by ER-TR9 and polyclonal anti-SIGN-R1 antibodies. Following transfection with SIGN-R1, cell lines become competent to endocytose dextrans. The dextran localizes primarily to compartments lacking transferrin receptor and the LAMP-1 CD107a panlysosomal antigen. Therefore, SIGN-R1 mediates the uptake of dextran polysaccharides, and it is predominantly expressed in the macrophages of the splenic marginal zone and lymph node medulla.     

Building research administration applications for the academic health center: a case study.

The academic health center information environment is saturated with information of varying quality and overwhelming quantity. The most significant challenge is transforming data and information into knowledge. The University of Cincinnati Medical Center's (UCMC) focus is to develop an information architecture comprising data structures, Web services, and user interfaces that enable individuals to manage the information overload so that they can create new knowledge. UCMC has accomplished much of what is reported in this article with the help of a four-year Integrated Advanced Information Management Systems (IAIMS) operation grant awarded by the National Library of Medicine in 2003. In the UCMC vision for knowledge management, individuals have reliable, secure access to information that is filtered, organized, and highly relevant for specific tasks and personal needs. Current applications and tool sets will evolve to become the next generation knowledge management applications or smart digital services. When smart digital services are implemented, silo applications will disappear. A major focus of UCMC's IAIMS grant is research administration. Testing and building out existing and new research administration applications and digital services is underway. The authors review UCMC's progress and results in developing a software architecture, tools, and services for research administration. Included are sections on the evolution to full integration, the impact of the work at UCMC to date, lessons learned during this research and development process, and future plans and needs.     

Double-blind, controlled study of clemastine fumarate, chlorpheniramine and placebo in patients with seasonal allergic rhinitis.

A whole body plethysmograph (body box) equipped with a flow meter (see Figure 1) was used for objective quantification of the effects of single doses of clemastine fumarate 2.68 mg, chlorpheniramine 4 mg and placebo in a double-blind study of 48 patients with seasonal allergic rhinitis. This technique offers an objective means of assessing drug effects on nasal congestion and obstruction. Before the development of whole body plethysmography, only subjective assessments of antihistamines' effects on nasal blockage or congestion were available. These subjective reports usually noted that nasal blockage or congestion was refractory to antihistamines or minimally relieved by them. However, in this study, nasal and oral airway resistances, each measured by whole body plethysmography, were lowered by clemastine fumarate and chlorpheniramine. These results were corroborated by the patients' and physician's assessments of changes in symptom severity and the physician's evaluation of intranasal photographs taken for each patient. Oral airway resistance of patients treated with clemastine fumarate was improved to a significantly greater extent than in patients receiving placebo. At two hours post-drug, patients receiving clemastine fumarate usually showed a greater response in most assessments than those receiving chlorpheniramine, and the trend of most comparisons was clearly in favor of clemastine fumarate. Patients in all three treatment groups experienced drowsiness but both incidence and severity were lower with clemastine fumarate.     

Psychophysiological correlates of induced headaches

The psychophysiological correlates of induced headaches were examined. Subjects with frequent muscle-contraction headaches, frequent migraine headaches, or infrequent headaches were exposed to a 1-h cognitive stressor while multiple electromyographic and cardiovascular measures were monitored. The stressor was associated with significant changes in all psychophysiological measures. Eleven of 16 headache subjects and 2 of 8 control subjects developed headaches. Significant associations between several psychophysiological variables and headache occurrence were found and individual differences in the association between psychophysiological variables and headaches intensity were examined. The results were consistent with the hypothesized role of cardiovascular factors in the pathophysiology of muscle-contraction headache. This was the first controlled demonstration of headaches occurring as a function of environmental stressors.This research was supported by Grant 5-R01-NS-1875 from the National Institute of Health.     

Hand involvement in Schmid metaphyseal chondrodysplasia

Schmid metaphyseal chondrodysplasia (Schmid MCD, MIM 156500) is caused by mutations in the COL10A1 gene and is clinically characterized by short stature, bowed legs, and a waddling gait. Radiographic findings include anterior cupping, sclerosis and splaying of the ribs, diffuse metaphyseal flaring, and irregularity that is most pronounced at the knees, coxa vara, and femoral bowing. We reviewed the radiographs of Schmid MCD patients at the International Skeletal Dysplasia Registry in Los Angeles for evidence of hand involvement. We found hand involvement in 47% (7/15) of cases included in our analysis. These changes were subtle and consisted of shortening of the tubular bones and metaphyseal cupping of the proximal phalanges and metacarpals. Mild hand involvement is a common feature of Schmid MCD.     

Effect of High Doses of Radiation on Human Neutrophil Chemotaxis, Phagocytosis and Morphology

Human neutrophils were exposed to varying amounts of ionizing radiation up to 1,000,000 rad and evaluated as to their ability to respond to chemotactic stimuli and phagocytize and kill bacteria. Striking morphologic and functional resistance to radiation was apparent. At doses up to 5,000 rad there was little or no impairment of chemotaxis. As the dosage increased to 50,000 rad, chemotaxis decreased to approximately 50% of nonirradiated control values. At very high doses of radiation (250,000 to 1,000,000 rad) neutrophils failed to respond significantly to chemotactic stimuli. Effects of radiation as measured by phagocytosis and the degree of ultrastructural change paralleled the chemotaxis results.     

Peak Identification in Visual Evoked Potentials

Waveform patterns evoked by 4 intensities of flash in normal subjects were studied in relation to intersubject variability. Time-frequency distribution curves of all peaks occurring between 11 and 280 msec after flash onset and meeting minimal criteria were obtained from 46 males. These distributions closely corresponded to similar data reported by others for single intensity stimulation. An algorithm was developed which identified in 67 to 100% of instances a single “peak event’ within the time ranges of each of 6 peak distributions. Many peak events appeared and disappeared within the 4 intensity sets of individuals. Latencies were obtained for these peak events. Application of the algorithm to a replicate sample of 29 Ss, which included 8 females, indicated generalizability. Test-retest data on 15 Ss showed its reliability. The data suggest that methodology significantly contributes to the variability of peak identification among subjects. This may be reduced by employing multiple intensities of stimulation.