The CD100-CD72 interaction: a novel mechanism of immune regulation.

CD100 is a 150 kDa transmembrane protein that belongs to the semaphorin family. Many members of the semaphorin family are known to play crucial roles in axon guidance, acting as chemorepulsive factors during neuronal development. CD100 is the first member of the semaphorin family for which crucial roles in the immune system have been identified. Although plexin-B1 has been shown to be the receptor for CD100 in nonlymphoid tissues, CD72 functions as its receptor in lymphoid tissues. CD100 plays a nonredundant role in the immune response by a unique mechanism that involves switching off the negative signals mediated by CD72.     

Intravenous immunoglobulin prevents experimental autoimmune myositis in SJL mice by reducing anti-myosin antibody and by blocking complement deposition.

High-dose intravenous immunoglobulin (IVIG) therapy has been effective in many autoimmune and systemic inflammatory diseases including polymyositis (PM) and dermatomyositis (DM). In the present study we evaluated the efficacy of IVIG using experimental models of PM and DM. An experimental autoimmune myositis (EAM) model was produced in SJL/J mice by an immunization with rabbit myosin B (MB) fraction. In this model, the plasma level of anti-MB antibody was elevated, and mouse IgG and complement C3 were deposited in the muscle fibres. Administration of IVIG dose-dependently reduced the incidences of necrotic and inflammatory changes in the skeletal muscle. IVIG treatment also decreased the elevation of anti-MB antibody level, as well as the deposition of IgG and C3. We next evaluated the effect of IVIG in adoptive EAM mice made by an intravenous injection of lymph node cells previously stimulated with MB. Adoptive EAM mice showed similar lesions in skeletal muscle as EAM mice and IVIG inhibited the lesion development. In vitro experiments demonstrated that IVIG inhibited complement-mediated lysis of human erythrocytes sensitized with anti-human erythrocyte antibodies. The binding of C1q, C4 and C3 to the same cells was also inhibited by IVIG. Taken together these findings suggest that IVIG prevents the development of myositis in EAM and adoptive EAM models by several mechanisms, such as reducing anti-myosin antibody and by blocking complement activation. Our present findings might account for the clinical efficacy of IVIG in PM and DM patients.     

Deleterious effects of lymphocytes at the early stage of neurodegeneration in an animal model of amyotrophic lateral sclerosis

Background  

Non-neuronal cells, such as microglia and lymphocytes, are thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Previous studies have demonstrated neuroprotective effects of lymphocytes at the end stage of ALS, partly through induction of alternatively activated microglia (M2 microglia), which are neuroprotective. In this study, we investigated the role of lymphocytes in the early stage of the disease using an animal model of inherited ALS.     

Lip closing pressure and spoon management in passive spoon feeding

To determine the sources of lip closing pressure (P(LC) ) generation during passive spoon feeding, we used a fine pressure transducer glued into a wooden spoon, as well as electromyography (EMG) of the upper and lower lips and the submental muscle complex, in normal adult volunteers (average age 24·5 years). An assistant fed a seated subject 0·6 mL of yogurt and then withdrew the spoon from the subject's closed mouth. The spoon was held at an angle of 0° (i.e. in the naso-auricular plane) during serving and at either 0° or 60° during withdrawal. We detected simultaneous increases in P(LC) and in EMG activity in the lips and the submental muscle complex. The maximum P(LC) was significantly higher at 60° [65 ± 11 g cm(-2) (mean ± s.e.m)] than at 0° (42 ± 8 g cm(-2)). The former was correlated with the maximum EMG amplitude, which was analysed by using the mean of the root-mean-square EMG and presented as a percentage of the maximum EMG obtained in the lower lip region and the submental muscle complex during subsequent swallowing in each subject. In conclusion, in healthy adult subjects, perioral muscles of the lower lip region and the submental muscle complex participate in P(LC) generation, particularly at a steep spoon withdrawal angle. The results suggest that a steep withdrawal angle not only increases P(LC) but also promotes these muscles' activities in passive spoon feeding.     

Effects of methylergometrine and oxytocin on blood loss and uterine contraction during cesarean section

BACKGROUND: The effects of intravenous oxytocics on blood loss and uterine contraction during cesarean section were studied in 136 parturients. METHODS: The subjects were randomized to receive either methylergometrine 0.2 mg bolus (MEM group; n = 34), oxytocin 10 IU over 30 seconds (OX 30 s group; n = 34), oxytocin 10 IU over 5 minutes (OX 5 m group; n = 34) or oxytocin 10 IU over 15 minutes (OX 15 m group; n = 34). The subjects received spinal anesthesia with 11-12 mg of intrathecal isobaric bupivacaine (0.5%). Additional intramyometrial prostaglandin F2alpha (PGF2alpha) was administered when obstetrician diagnosed uterine atony. We analyzed total amount of blood loss including amniotic fluid and number of parturients that received additional intramyometrial PGF2alpha to evaluate uterine contraction. RESULTS: The amounts of blood loss in the OX 30 s and OX 5 m groups were significantly lower than in the MEM group, and the numbers of parturients received additional PGF2alpha in all the oxytocin treat ment groups were significantly lower than in the MEM group (P < 0.05). There were no significant differences in blood loss and uterine contractior among the oxytocin treatment groups. CONCLUSIONS: Intravenous oxytocin 10 IU over 30 seconds to 15 minutes was effective to decrease blood loss and uterine contraction than intravenous methylergometrine 0.2 mg bolus.     

Determining the plasma concentration of ketamine that enhances epidural bupivacaine-and-morphine-induced analgesia

N-methyl-D-aspartate (NMDA) receptor antagonists enhance opioid-induced analgesia. The plasma concentration of ketamine, an NMDA receptor antagonist that enhances epidural morphine-and-bupivacaine-induced analgesia, is not known. We examined 24 patients with lung carcinoma or metastatic lung tumor who underwent video-assisted thoracic surgery in a placebo-controlled, double-blind manner 4 h after emergence from anesthesia. The morphine + ketamine group (n = 8) and morphine + placebo group (n = 8) received 5 mL volume of 2.5 mg morphine and 0.25% bupivacaine and the placebo + ketamine group (n = 8) received 5 mL volume of saline and 0.25% bupivacaine epidurally at the end of skin closure. Four hours after this anesthesia, in the morphine + ketamine and placebo + ketamine groups, ketamine was administered to successively maintain a stable plasma ketamine concentration of 0, 10, 20, 30, 40, and 50 ng/mL by a target-controlled infusion device, and patients assessed the levels of pain at rest, pain on coughing, somnolence (drowsiness), and nausea using a 100-mm visual analog scale (VAS). In the morphine + placebo group, a placebo (saline) was similarly administered instead of ketamine. In the morphine + ketamine group, the VAS scores for pain at rest and pain on coughing significantly decreased on ketamine administration at a plasma concentration of 20 ng/mL or larger compared with the respective baseline VAS scores (P < 0.05 each). In the placebo + ketamine group, the VAS scores for pain at rest and pain on coughing did not significantly change at any plasma concentration of ketamine as compared to the morphine + placebo group. In the morphine + ketamine group, a plasma concentration of ketamine larger than 20 ng/mL did not further reduce VAS scores for pain at rest and pain on coughing. The VAS scores for drowsiness were comparable among the three groups at any plasma concentration of ketamine. Ketamine at a plasma concentration of 20 ng/mL or larger may enhance epidural morphine-and-bupivacaine-induced analgesia. As an adjunct with epidural morphine-and-bupivacaine and considering the safety of small doses, the minimal plasma concentration of ketamine given IV may be approximately 20 ng/mL.     

Thoracic epidural pressure and peripheral venous pressure in the lower extremity during supine hypotensive syndrome

BACKGROUND: After induction of spinal anesthesia, thoracic epidural pressure and left saphenous venous pressure were monitored and recorded during supine hypotensive syndrome in 8 pregnant patients who underwent elective cesarean section. METHODS: A 22 G venous catheter was inserted into the left saphena, and an epidural catheter for 18 G needles was positioned 5 cm cephalad in the epidural space through a Tuohy needle at the T 11-12 intervertebral space. Each catheter was connected to a pressure transducer, and recording was started in a supine position immediately after induction of spinal anesthesia with 0.5% isobaric bupivacaine at the L 3-4 intervertebral space. RESULTS: In all patients, epidural pressure and peripheral venous pressure synchronously increased as soon as they began to recover from hypotension and tachycardia regardless of uterine displacement to the left. CONCLUSIONS: The synchronous increase in both pressures was late after the hypotension probably because sympathetic block with spinal anesthesia inhibited vasoconstriction of the lower extremity, a factor to compensate for supine hypotensive syndrome. Only collateral flow via epidural venous plexus emptying into azygos system could not compensate for decreased venous return to the right atrium from obstructed inferior vena cava, and differences in the degree of compression of the inferior vena cava by gravid uterus would affect the recovery from supine hypotension.     

CDw40 and BLCa-specific monoclonal antibodies detect two distinct molecules which transmit progression signals to human B lymphocytes

Two monoclonal antibodies (mAb), MA6 and G28-5, have the common property of detecting markers expressed on both B lymphocytes and carcinomas: BLCa (B lymphocyte carcinoma cross-reacting antigen) and CDw40 (Bp50). A comparison of the reactivity of these mAb revealed that MA6 and G28-5 detect distinct epitopes with different cell line and tissue distributions. L cell transfectants expressing CDw40 were not bound by MA6 anti-BLCa, but were bound by G28-5 anti-CDw40. G28-5 or a CDw40-specific heterantiserum could not block the migration of BLCa, while MA6 antibody could. These results indicate that CDw40 and BLCa are distinct surface molecules. Both G28-5 anti-CDw40 and MA6 anti-BLCa mAb could provide progression signals for B cells activated by appropriate B cell activators such as phorbol esters or anti-immunoglobulin; however, only G28-5 anti-CDw40 and not MA6 was co-stimulatory with the anti-CD20 competence signal, demonstrating a clear difference in the CDw40 and BLCa-mediated progression signals. Apparently, these molecules, although structurally distinct, have related functions in B cell activation.