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.     

Differential effects of (S)- and (R)-enantiomers of albuterol in a mouse asthma model

BACKGROUND: (R)- and (S)-Enantiomers of albuterol likely exert differential effects in patients with asthma. The (R)-enantiomer binds to the beta2-adrenergic receptor with greater affinity than the (S)-enantiomer and is responsible for albuterol's bronchodilating activity. (S)-Albuterol augments bronchospasm and has proinflammatory actions. OBJECTIVE: The study aim was to determine whether the (S)-enantiomer, in contrast to the (R)-enantiomer, has adverse effects on allergic airway inflammation and hyperresponsiveness in a mouse asthma model. METHODS: Mice sensitized to ovalbumin (OVA) intraperitoneally on days 0 and 14 were challenged with OVA intranasally on days 14, 25, and 35. On day 36, 24 hours after the final allergen challenge, the effect of the (R)- and (S)-enantiomers of albuterol (1 mg x kg(-1) x d(-1) administered by means of a miniosmotic pump from days 13-36) on airway inflammation and hyperreactivity was determined. RESULTS: In OVA-sensitized/OVA-challenged mice, (R)-albuterol significantly reduced the influx of eosinophils into the bronchoalveolar lavage fluid and airway tissue. (R)-Albuterol also significantly decreased airway goblet cell hyperplasia and mucus occlusion and levels of IL-4 in bronchoalveolar lavage fluid and OVA-specific IgE in plasma. Although (S)-albuterol significantly reduced airway eosinophil infiltration, goblet cell hyperplasia, and mucus occlusion, it increased airway edema and responsiveness to methacholine in OVA-sensitized/OVA-challenged mice. Allergen-induced airway edema and pulmonary mechanics were unaffected by (R)-albuterol. CONCLUSION: Both (R)- and (S)-enantiomers of albuterol reduce airway eosinophil trafficking and mucus hypersecretion in a mouse model of asthma. However, (S)-albuterol increases allergen-induced airway edema and hyperresponsiveness. These adverse effects of the (S)-enantiomer on lung function might limit the clinical efficacy of racemic albuterol.     

Early rehabilitation program in postmastectomy patients: a prospective clinical trial

The purpose of this study was to determine whether 20 patients who received an early postmastectomy rehabilitation treatment program showed more improvement in range of shoulder motion and functional activities than 13 patients who received instruction for exercise only. Data were obtained at preoperatively, three days after operation, at discharge and at postdischarge one month for each patient on parameters such as range of motion of the ipsilateral shoulder joint, upper extremity circumferential measurements, as well as 10 elements of shoulder function. Postoperatively, both groups showed an increased range of motion of the shoulder joint and improved functional activities, but the group that received postoperative rehabilitation management had a better range of shoulder motion and less difficulty in five items for functional assessment. This study also showed that an early rehabilitation program did not increase postoperative complications. We concluded that an early rehabilitation program or intensive instruction program only by a well-trained physical therapist or physiatrist was beneficial to postmastectomy patients in regaining the function and range of shoulder motion, and significantly better in a rehabilitation group.     

Villous adenoma of the bile ducts: a case report and a review of the reported cases in Korea

Villous adenomas are benign epithelial lesions with malignant potential which can occur at any site in the gastrointestinal tract. They are usually encountered in the rectum and colon, less frequently in the small bowel and very rarely in the biliary trees. Nine cases of bile duct villous adenomas have been reported in the literature. However, 4 cases of bile duct villous adenomas have been reported in the Korean literature. Recently, we experienced a case of villous adenoma in the common hepatic duct in a 77-year-old man presenting with obstructive jaundice in which preoperative histologic diagnosis of villous adenoma played a critical role in managing this patient. Herein, we present a case report of bile duct villous adenoma and a review of the reported cases in Korea to help define and manage this rare disease entity in the bile ducts. In addition, confusing nomenclature of bile duct adenomas is discussed.     

Immunoelectron microscopic identification of human NK cells by FITC-conjugated anti-Leu-11a and biotinylated anti-Leu-7 antibodies

Human natural killer (NK) cells have been reported to express various surface antigens. The majority and the most functionally potent NK cells are Leu-11a (NKP-15) positive cells. Only a small number of functional NK cells express Leu-7 (HNK-1) antigen. In the present study, we have established techniques for immunoelectron microscopic identification of NK cells by mouse monoclonal FITC-conjugated anti-Leu-11a and biotinylated anti-Leu-7 antibodies. Ficoll-Hypaque-isolated peripheral blood lymphocytes (PBL) were reacted with the specific antibodies before or after fixation in a 1% glutaraldehyde/1% paraformaldehyde fixative. Prefixation labeling of viable cells with the antibodies was carried out at 4 degrees C or 37 degrees C. Cells prelabeled with anti-Leu-11a antibody were reacted with secondary antibodies either before or after fixation. Anti-Leu-7 antibody was stained directly via an avidin-biotin-peroxidase (ABC) system, anti-Leu-11a antibody was stained indirectly by the ABC immunoperoxidase procedure via a biotinylated anti-mouse IgG secondary antibody or by a 10 nm or 40 nm colloidal gold-labeled anti-mouse IgG antibody. Results indicate that Leu-7 antigen could be localized by incubation with the specific antibody either before or after 20 min fixation; however, Leu-11a antigen was totally abrogated following the same fixation procedure. The Leu-11a antigen was well stained by the methods of prefixation labeling of cells with anti-Leu-11a antibody and incubation with a biotinylated secondary antibody and the ABC system after fixation. With respect to colloidal gold labeling, better results were obtained when cells were reacted with the gold-labeled antibodies immediately after incubation with anti-Leu-11a antibody but before fixation. Ultrastructurally both Leu-7 positive (+) and Leu-11a positive (+) cells shared common ultrastructural features associated with large granular lymphocytes. Using the above described techniques, we found approximately 2-5% Leu-7+ and 9-15% Leu-11a+ cells in the PBL of healthy donors. The overall results suggest that Leu-11a antigen is more sensitive to glutaraldehyde/paraformaldehyde fixation than Leu-7, since it can be localized only by prefixation labeling procedures; the ABC immunoperoxidase procedure is an ideal technique for labeling NK cells for light and electron microscopic enumeration; the immunogold method provides an adequate technique for labeling NK cells which are designated for ultracytochemical studies.     

Frequency-to-voltage conversion in the pyramidal tract neuron: an important role of the inhibitory postsynaptic potential

Frequency-coded impulses are known to be converted into postsynaptic potentials (PSPs) at the synapse of a target neuron. This can be termed frequency-voltage (F-V) conversion. Studies on this problem in pyramidal tract neurons (PTNs) showed that not only the amplitude but also the duration of depolarizing PSPs was determined as a function of the input impulse frequency. Two opposite patterns of F-V conversion were observed following activation of two input systems to PTNs. Inhibitory postsynaptic potentials were found to play an important role in the regulation of the duration of PSPs by curtailing excitatory post-synaptic potentials.     

Isometric and isokinetic torque curves at the knee joint

Isometric and isokinetic torques of bilateral quadriceps and hamstrings were measured with Isokinetic Rehabilitation and Testing System (Model No. Cybex 340) on 40 normal untrained subjects, 20 males and 20 females, ranging between the ages of 23 and 35 years. The mean peak isometric and isokinetic torque values of both muscle groups showed no significant differences between dominant (right) and nondominant (left) limbs in both sexes; however there were significant differences between the male and the female. As the angular velocity increased, the peak torque significantly decreased, and the point of peak torque output occurred significantly later in the range of motion for quadriceps and hamstrings (p less than 0.01). There were no significant changes in the hamstrings to quadriceps (H/Q) ratios as the angular velocity increased. However, there were significant differences of mean H/Q ratio between male and female (p less than 0.01). Height had significant positive correlation with peak isometric and isokinetic torques for both quadriceps and hamstrings (p less than 0.01). Weight was found to correlate significantly with peak isometric and isokinetic torques (p less than 0.01). The mean isometric torques were significantly higher than the mean isokinetic torques for any joint angles in both sexes (p less than .01).     

Characteristics and diagnoses of cockroach-sensitive bronchial asthma.

Bronchial asthma with cockroach hypersensitivity is prevalent among urban asthmatic populations. To elucidate characteristics of cockroach asthma, we analyzed 592 consecutive urban Chicago asthmatic patients retrospectively. Allergy skin testing (AST) with common inhalants, serum total IgE, and cockroach-specific IgE (IgE-CR) antibodies were measured. Some cockroach asthmatics were studied further for bronchial reactivity in vivo and histamine releasability (HR) in vitro against cockroach allergen (CRa), and diagnostic accuracy for asthma was analyzed. Clinical characteristics were evaluated and compared with those of ragweed asthmatics and asthmatics in general. Two hundred eighty-three (196 women, 87 men) were reactive to CRa by AST. The average age and duration of cockroach asthma were 30.4 and 15.1 years, respectively. Steroid dependency of the cockroach asthma was higher (32%) than those of general asthmatics (P less than .05) and ragweed asthma (P less than .05). IgE level was elevated (geometric mean 413.2 IU/mL), higher than that of general asthmatics (P less than .001), and 87% showed IgE level higher than 100 IU/mL. IgE-CR and BPT-CR were positive in 61% (175 tested) and in 87% (166 tested), respectively. Sensitivity and specificity of skin test were 99% and 40%, while those of IgE-CR were 91% and 58%, respectively. IgE-CR increased probability of cockroach asthma from 87% to 91%. BPT with CRa was correlated well with the HR of leukocytes (P less than .0001). Thus, cockroach asthma is a severe allergic asthma and can be diagnosed accurately by skin test plus BPT or skin test plus HR.     

DNA prime followed by protein boost enhances neutralization and Th1 type immunity against FMDV

Prime-boost strategy has been exhibited its potency to enhance immune responses, which would be important to the success to develop a vaccine against the foot-and-mouth disease virus (FMDV). An eukaryotic expression construct encoding the FMDV capsid VP1 protein with a recombinant VP1 protein or a commercial FMDV vaccine were tested in the prime-boost strategy in mice and cattle trials. The levels of induced specific antibodies, T cell proliferations, and DTH activities were significantly higher in the prime-boost groups than in those vaccinated with DNA, protein or FMDV vaccine alone. More importantly, the levels of neutralizing antibodies in the former groups were significantly higher than others and could last for at least four months in cattle trials. This study suggests that the prime-boost strategy significantly improves the effective immunity and may provide a longer protection against FMDV infection.