iNKT cells, a friend or a foe for autoimmune disease and allergy?]

iNKT cells are a unique subset of CD1-restricted T lymphocytes that express T cell receptor (TCR) and some NK receptors. iNKT cells express an invariant TCRalpha chain composed of Valpha14-Jalpha18 segments in mice and Valpha24-Jalpha18 segments in humans associated with TCRbeta chains using a restricted set of Vbeta. iNKT cells recognize glycolipid antigens such as alpha-galactosylceramide (alpha-GC) presented by CD1d, non-pormorphic MHC class I-like molecule, and rapidly secrete large amounts of cytokines including IL-4 and IFN-gamma upon activation. Due to its potent ability to produce a variety of cytokines, iNKT cells are involved in a various kinds of immunoregulation. iNKT cells play a regulatory role in some disease models such as type I diabetes in NOD mice. In contrast, iNKT cells exaggerate the pathogenesis such as arthritis, allergic airway inflammation and atherosclerosis. In addition, iNKT cells are an attractive target for immunotherapy because several different synthetic glycolipid antigens to modify the function of iNKT cells are available. In this review, we examine the potential roles of NKT cells in the pathogenesis of a variety of diseases including autoimmunity , allergy, infection and cancer. Additionally, we discuss on the recent advances in glycolipid therapy for these disease models.     

Fluctuations in Tumor Blood Flow under Normotension and the Effect of Angiotensin II-induced Hypertension

To elucidate the significance of angiotensin II (AID-induced hypertension chemotherapy, changes of tissue blood flow both in normal subcutis and in tumors (AH109A, LY80) were measured with the hydrogen gas clearance method. A newly-developed anesthetic machine was used to keep the animals' condition constant. Tissue blood flow in normal subcutis and tumors always fluctuated with time under normotension. The nature and the rate of fluctuation in tumor Wood flow were almost identical in two different types of tumors. However, the fluctuation of blood flow in tumor and that in normal subcutis were almost always inversely related when blood flows in these different tissues were measured simultaneously, i.e., when tissue blood flow in normal subcutis decreased, tumor blood flow increased, and vice versa. The findings supported the idea that the connection mode between the tumor vascular bed and normal vascular bed is a parallel circuit. Vascular resistance in the normal vascular bed under All-induced hypertension seemed to be greater than that under normotension, because the All-increased tumor blood flow always exceeded the maximum tumor blood flow under normotension. Due to the fluctuations of tumor blood flow, no-flow or low-flow areas, resistant to delivery of anti-cancer drugs, moved sporadically within the tumor under the normotensive condition. However, good conditions for drug delivery to tumor tissue were induced by All-induced hypertension.     

Hydrolysis of phenyl esters in cyclodextrin-polymer systems

The catalytic hydrolysis of phenyl esters in systems containing ß-cyclodextrin (ß-CD) and polyelectrolytes was investigated. Poly(methacrylic acid) was found to exhibit an inhibition effect on the hydrolysis, while poly(sodium styrenesulfonate) (NaPSS) shows a pronounced acceleration effect on the hydrolysis: the larger the molecular weight and the lower the degree of substitution, the greater is the acceleration effect. On the other hand, sodium ethylbenzenesulfonate and sodium dodecylbenzenesulfonate inhibit the reaction. The acceleration of the reaction in presence of NaPSS is attributed to the concentration of ß-CD and the substrate esters near to the chain of the macromolecule, through inclusion effects and hydrophobic interactions.     

Effects of ONO-3708, an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, on platelet aggregation and thrombosis

The beneficial effects of an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, 7-[2 alpha,4 alpha-(dimethylmethano)-6 beta-(2-cyclopentyl-2 beta- hydroxyacetamido)-1 alpha-cyclohexyl]-5(Z)-heptenoic acid (ONO-3708) on thrombosis were examined. ONO-3708 at 0.1-3 microM inhibited the human platelet aggregation induced by thromboxane A2, prostaglandin H2, collagen, ADP (secondary phase) and epinephrine (secondary phase) without affecting prostanoid synthesis and the content of cyclic AMP in platelets. The in vivo effects, on coronary thrombosis in this case, were examined in two canine models. ONO-3708, 3 to 300 micrograms/kg i.v., prevented dose dependently the coronary thrombosis induced by partial obstruction of the coronary artery. ONO-3708, 3 micrograms/kg per min i.v., significantly prevented electrically stimulated coronary thrombosis without affecting systemic blood pressure and heart rate. These results indicate that the thromboxane A2/prostaglandin endoperoxide receptor could play an important role in the pathogenesis of thrombosis and that ONO-3708 may have therapeutic advantages in preventing thrombosis.     

Normothermic cardiopulmonary bypass: effect on the incidence of persistent postoperative neurological dysfunction following coronary artery bypass graft surgery

We retrospectively reviewed the records of 250 consecutive patients undergoing coronary artery bypass graft surgery (CABG) from January 1994 through January 1996 to determine the incidence of persistent postoperative neurological dysfunction after CABG and to compare normothermic and moderate hypothermic cardiopulmonary bypass (CPB). Normothermic CPB was used in 128 patients (36°–37°C) and hypothermic CPB (27°–28°C) in 122 patients. Postoperative neurological dysfunction included focal motor deficits, delayed recovery of consciousness (>24h) after surgery, and seizures within 1 week postoperatively. Persistent neurological dysfunction was diagnosed if complete resolution had not occurred within 10 days of surgery. The incidence of persistent postoperative neurological dysfunction was 4.1% in the hypothermic CPB group and 2.3% in the normothermic CPB group. There were no statistically significant differences between the two groups (P=NS). These results suggest that normothermic CPB did not increase the incidence of persistent postoperative neurological dysfunction compared to hypothermic CPB.     

Partial hepatic resection under intermittent hepatic inflow occlusion in patients with chronic liver disease.

A partial hepatic resection was performed in 13 patients with chronic liver disease using intermittent hepatic inflow occlusion. Eleven patients had liver cirrhosis and two had chronic hepatitis. Seven patients were classified as Child's grade A and six as Child's grade B before operation. Dissection of the hepatic parenchyma was performed during intermittent inflow occlusion. The time of clamping and declamping was 10-20 min and 5-8 min, respectively. Postoperative data on liver function showed recovery to preoperative levels by about 10 days after operation. There were no life-threatening complications. These results indicate that intermittent hepatic inflow occlusion can be achieved easily and safely to allow non-anatomical resection in patients with chronic liver disease.     

Takayasu's arteritis and mitral stenosis

A 44-year-old housewife was found to have coarctation of the abdominal aorta secondary to Takayasu's arteritis. Since she also had mitral stenosis, possible etiological relation between Takayasu's arteritis and mitral stenosis is suspected.     

Tumor-specific binding of radiolabeled G-22 monoclonal antibody in glioma patients.

Iodine-131-labeled G-22 monoclonal antibody F(ab')2 fragment reaching specifically with a glioma-associated surface glycoprotein was administered to 12 glioma patients to investigate its use in radioimaging of intracranial gliomas. No immediate or delayed side effects were attributable to antibody injection. Nine patients received the radiolabeled complex intravenously. The images of low-grade gliomas were generally poor and disappeared within 4 days. High-contrast images were obtained beyond the 7th day in high-grade gliomas except one case in the pineal region. Three patients received intraventricular or intratumoral administration. Clear images of all tumors were demonstrated from the 2nd until later than the 7th day. One patient with cerebrospinal fluid (CSF) dissemination of brainstem glioma demonstrated negative CSF cytology after intraventricular administration.