Comparison of MR Imaging and Dual-Energy CT for the Evaluation of Cartilage Invasion by Laryngeal and Hypopharyngeal Squamous Cell Carcinoma.

BACKGROUND AND PURPOSE: Dual-energy CT can distinguish iodine-enhanced tumors from nonossified cartilage and has been investigated for evaluating cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinomas. In this study, we compared the diagnostic accuracy of MR imaging and of a combination of weighted-average and iodine overlay dual-energy CT images in detecting cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinomas, in particular thyroid cartilage invasion. MATERIALS AND METHODS: Fifty-five consecutive patients who underwent 3T MR imaging and 128-slice dual-energy CT for preoperative initial staging of laryngeal or hypopharyngeal squamous cell carcinomas were included. Two blinded observers evaluated laryngeal cartilage invasion on MR imaging and dual-energy CT using a combination of weighted-average and iodine-overlay images. Pathologic findings of surgically resected specimens were used as the reference standard for evaluating sensitivity, specificity, and the areas under the receiver operating characteristic curve of both modalities for cartilage invasion by each type of cartilage and for all cartilages together. Sensitivity and specificity were compared using the McNemar test and generalized linear mixed models. RESULTS: Dual-energy CT showed higher specificity than MR imaging for diagnosing all cartilage together (84% for MR imaging versus 98% for dual-energy CT, P < .004) and for thyroid cartilage (64% versus 100%, P < .001), with a similar average area under the curve (0.94 versus 0.95, P = .70). The sensitivity did not differ significantly for all cartilages together (97% versus 81%, P = .16) and for thyroid cartilage (100% versus 89%, P = .50), though there was a trend toward increased sensitivity with MR imaging. CONCLUSIONS: Dual-energy CT showed higher specificity and acceptable sensitivity in diagnosing laryngeal cartilage invasion compared with MR imaging.

Early results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results. METHODS: Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival. RESULTS: Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed. CONCLUSIONS: Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.

Randomized clinical trial comparing standard diet with perioperative oral immunonutrition in total gastrectomy for gastric cancer.

BACKGROUND: Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear. METHODS: This was a randomized phase III clinical trial of addition of eicosapentaenoic acid-rich nutrition to a standard diet in patients having total gastrectomy for gastric cancer. Patients were randomized to either a standard diet or standard diet with oral supplementation of an eicosapentaenoic acid (ProSure®), comprising 600 kcal with 2·2 g eicosapentaenoic acid, for 7 days before and 21 days after surgery. The primary endpoint was percentage bodyweight loss at 1 and 3 months after surgery. RESULTS: Of 127 eligible patients, 126 were randomized; 124 patients (61 standard diet, 63 supplemented diet) were analysed for safety and 123 (60 standard diet, 63 supplemented diet) for efficacy. Across both groups, all but three patients underwent total gastrectomy with Roux-en-Y reconstruction. Background factors were well balanced between the groups. Median compliance with the supplement in the immunonutrition group was 100 per cent before and 54 per cent after surgery. The surgical morbidity rate was 13 per cent in patients who received a standard diet and 14 per cent among those with a supplemented diet. Median bodyweight loss at 1 month after gastrectomy was 8·7 per cent without dietary supplementation and 8·5 per cent with eicosapentaenoic acid enrichment (P = 0·818, adjusted P = 1·000). Similarly, there was no difference between groups in percentage bodyweight loss at 3 months (P = 0·529, adjusted P = 1·000). CONCLUSION: Immunonutrition based on an eicosapentaenoic acid-enriched oral diet did not reduce bodyweight loss after total gastrectomy for gastric cancer compared with a standard diet. Registration number: UMIN000006380 ( http://www.umin.ac.jp/).

Multicentre observational study of quality of life after surgical palliation of malignant gastric outlet obstruction for gastric cancer.

BACKGROUND: Quality of life (QoL) is a key component in decision-making for surgical palliation, but QoL data in association with surgical palliation in advanced gastric cancer are scarce. The aim of this multicentre observational study was to examine the impact of surgical palliation on QoL in advanced gastric cancer. METHODS: The study included patients with gastric outlet obstruction caused by incurable advanced primary gastric cancer who had no oral intake or liquid intake only. Patients underwent palliative distal/total gastrectomy or bypass surgery at the physician's discretion. The primary endpoint was change in QoL assessed at baseline, 14 days, 1 month and 3 months following surgical palliation by means of the EuroQoL Five Dimensions (EQ-5D™) questionnaire and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were postoperative improvement in oral intake and surgical complications. RESULTS: Some 104 patients (23 distal gastrectomy, 9 total gastrectomy, 70 gastrojejunostomy, 2 exploratory laparotomy) were enrolled from 35 institutions. The mean EQ-5D™ utility index scores remained consistent, with a baseline score of 0·74 and the change from baseline within ± 0·05. Gastric-specific symptoms showed statistically significant improvement from baseline. The majority of patients were able to eat solid food 2 weeks after surgery and tolerated it thereafter. The rate of overall morbidity of grade III or more according to the Clavien-Dindo classification was 9·6 per cent (10 patients) and the 30-day postoperative mortality rate was 1·9 per cent (2 patients). CONCLUSION: In patients with gastric outlet obstruction caused by advanced gastric cancer, surgical palliation maintained QoL while improving solid food intake, with acceptable morbidity for at least the first 3 months after surgery. Registration number 000023494 (UMIN Clinical Trials Registry).

A New Statistical Model Identified Two-thirds of Clinical T1 Gastric Cancers as Possible Candidates for Endoscopic Treatment.

BACKGROUND: Clinical T1 gastric cancer has low metastatic potential to lymph nodes and is generally curable by local treatment. Endoscopic resection can preserve the whole stomach and does not impair the patient's quality of life; however, its indication is strictly limited to the subset of patients without nodal metastasis. The study was designed to predict reliably the patients without nodal metastasis based only on the clinical information. METHODS: We examined patients with clinical T1 disease who were treated with surgery. The clinically available information was evaluated for its ability to predict nodal metastasis by logistic regression model. Then, the predictive ability of the logistic regression model using the risk factors for nodal metastasis was evaluated by a receiver operating characteristic curve. RESULTS: A total of 511 patients were entered into this study. The clinical depth (cT1a or cT1b), maximal tumor diameter, and pathological type were confirmed to be significantly different between patients with and without nodal metastasis. The cutoff value of the tumor diameter differed depending on the histology and clinical depth: 79 mm for differentiated type and 48 mm for undifferentiated type in cT1a tumors, and 43 mm for differentiated type and 11 mm for undifferentiated type in cT1b tumors. According to these criteria, 348 of the 511 patients (68.1 %) were classified to have predictive N0 status. The negative predictive value was 95.7 % (95 % confidence interval 94.0-97.5 %). CONCLUSIONS: The predictive criteria based on the multivariate logistic model identified that almost two-thirds of the patients with clinical T1 gastric cancer were possible candidates for endoscopic treatment.

Preoperative serum hyaluronic acid level as a prognostic factor in patients undergoing hepatic resection for hepatocellular carcinoma.

BACKGROUND: Hyaluronic acid (HA) probably plays a critical role in tumorigenesis. The clinical significance of serum HA concentration in patients with hepatocellular carcinoma (HCC) remains to be elucidated. This study analysed the relationship between preoperative serum HA levels and prognosis after hepatic resection in patients with HCC. METHODS: Consecutive patients who underwent hepatic resection for HCC between September 1999 and March 2012 were included in this retrospective study. Serum HA levels were measured within 4 weeks before surgery by an immunoturbidimetric automated latex assay. The cut-off level for preoperative serum HA was validated using a time-dependent receiver operating characteristic (ROC) curve analysis. The prognostic impact of preoperative serum HA levels was analysed using Cox proportional hazards models. RESULTS: A total of 506 patients of median age 66 years (405 men, 80·0 per cent) were analysed. The median length of follow-up was 32 months. High serum HA levels (100 ng/ml or above) were associated with shorter recurrence-free survival (P < 0·001) (hazard ratio (HR) 1·50, 95 per cent confidence interval 1·17 to 1·93; P = 0·002) and overall survival (P = 0·001) (HR 1·46, 1·03 to 2·07; P = 0·033). In patients with HCC without severe liver fibrosis, serum HA level was correlated with multiple tumours (P = 0·039), early recurrence (P = 0·033), and poor recurrence-free (P < 0·001) and overall (P = 0·024) survival. CONCLUSION: High preoperative serum HA levels predict poor prognosis in patients with HCC after hepatic resection, and may serve as a future biomarker.

The extent of degeneration of cruciate ligament is associated with chondrogenic differentiation in patients with osteoarthritis of the knee.

OBJECTIVE: Degeneration in cruciate ligaments results from abnormal biomechanical stress and the aging process. Such degeneration is a common outcome in patients with osteoarthritis (OA) of the knee and contributes to the progression of OA. However, to date, there are no specific markers that can predict the extent of ligament degeneration. We hypothesized that the extent of degeneration has correlations to increased chondrogenic potential. METHODS: Twenty anterior cruciate ligaments (ACLs) and 30 posterior cruciate ligaments (PCLs) from 30 knees of 28 adult patients with OA at the time of total knee arthroplasty were used for the study. Degeneration was histologically assessed using a grading system. Expressions of Scleraxis (as a ligament cell marker) and Sry-type HMG box 9 (SOX9) (as a chondrogenic marker) were immunohistochemically assessed in each grade. RESULTS: We found the opposite expression pattern between Scleraxis and SOX9 according to the grade. The percentage of Scleraxis-positive cells decreased significantly by grade (60.9±23.7 in grade 1, 39.7±30.5 in grade 2, and 13.9±27.1 in grade 3, P<0.0001). In contrast, the percentage of SOX9-positive cells increased significantly by grade (2.5±4.9 in grade 1, 17.5±13.4 in grade 2, and 50.9±27.1 in grade 3, P<0.0001). Furthermore, co-localized expression of both Scleraxis and SOX9 was demonstrated in chondrocyte-like cells. CONCLUSIONS: This study indicates that chondrogenic differentiation is associated with the progression of degeneration in human ligaments. Our results suggest that the expression of SOX9 as a chondrogenic marker could be an indicator for the extent of degeneration in human ligaments. It remains to be elucidated whether suppression of chondrogenic differentiation can prevent progression of the degenerative process of cruciate ligaments in patients with OA.

Caspases: evolutionary aspects of their functions in vertebrates.

Caspases (cysteine-dependent aspartyl-specific protease) belong to a family of cysteine proteases that mediate proteolytic events indispensable for biological phenomena such as cell death and inflammation. The first caspase was identified as an executioner of apoptotic cell death in the worm Caenorhabditis elegans. Additionally, a large number of caspases have been identified in various animals from sponges to vertebrates. Caspases are thought to play a pivotal role in apoptosis as an evolutionarily conserved function; however, the number of caspases that can be identified is distinct for each species. This indicates that species-specific functions or diversification of physiological roles has been cultivated through caspase evolution. Furthermore, recent studies suggest that caspases are also involved in inflammation and cellular differentiation in mammals. This review highlights vertebrate caspases in their universal and divergent functions and provides insight into the physiological roles of these molecules in animals.

Characteristics of a newly developed dentomaxillofacial X-ray cone beam CT scanner (CB MercuRay): system configuration and physical properties.

OBJECTIVE: The purpose of this paper is to present the system configuration and physical properties of a new dentomaxillofacial X-ray cone beam CT system (CB MercuRay) being developed. METHODS: The system consists of an image intensifier and a cone beam X-ray source. There are two different models of this system, each with a different size image intensifier, 9" or 12". Each system has three field of view (FOV) modes. The 12" system has facial (F), panoramic (P) and implant (I) FOV modes. The 9" system has P, I and dental (D) modes. Images produced by these systems consist of 512 x 512 x 512 isotropic voxels. Physical properties such as resolution, noise and distortion of the images were evaluated in this study. Modulation transfer function (MTF) was measured using Boone's method. Image noise was measured as the standard deviation of the CT value in water. Circularity of the axial images yielded by the two models was measured using an 8 mm diameter acrylic pipe phantom. RESULTS: The resolving power at a MTF of 0.1 in the D mode was over 2.0 lp mm(-1), suggesting that this system yields images of high resolution. The standard deviation of the CT value in water was approximately 80, which is thought to be greater than that of conventional CT. The circularity of images of the pipe phantom was 99% of the ideal value. CONCLUSION: This study shows that our newly developed cone beam CT system produces high resolution three-dimensional volumetric images that will be useful for the examination of dentomaxillofacial disorders.

Involvement of death receptor Fas in germ cell degeneration in gonads of Kit-deficient Wv/Wv mutant mice.

Kit and its ligand stem cell factor (SCF) play a fundamental role in hematopoiesis, melanogenesis and gametogenesis. Homozygous W(v) mutant mice with a mutation in kit show abnormalities in these cell lineages. Fas is a member of the death receptor family inducing apoptosis. In this study, we generated double-mutant mice (W(v)/W(v):Fas(-/-)) and analyzed histologically their reproductive organs. In testes and ovaries of the double-mutant mice, testicular germ cells and oocytes were detected, respectively, whereas the same-aged W(v)/W(v) mice contained neither cells. In addition, inhibition of Kit signals by administration of anti-Kit mAb, which induces degeneration of testicular germ cells in vivo in wild-type mice, did not cause degeneration in Fas-deficient mice. In testicular germ cells of W(v)/W(v) mutant mice, an increase of Fas expression was observed in spermatogonia. Further, in vitro treatment with SCF was shown to downregulate Fas on fibroblasts expressing exogenous Kit through activation of PI3-kinase/Akt. All the results clearly indicate that Fas-mediated apoptosis is involved in germ cell degeneration accompanied by defects in Kit-mediated signals, and Kit signaling negatively regulates Fas-mediated apoptosis in vivo.

ER stress induces caspase-8 activation, stimulating cytochrome c release and caspase-9 activation.

Excess ER stress induces caspase-12 activation and/or cytochrome c release, causing caspase-9 activation. Little is known about their relationship during ER stress-mediated cell death. Upon ER stress, P19 embryonal carcinoma (EC) cells showed activation of various caspases, including caspase-3, caspase-8, caspase-9, and caspase-12, and extensive DNA fragmentation. We examined the relationship between ER stress-mediated cytochrome c/caspase-9 and caspase-12 activation by using caspase-9- and caspase-8-deficient mouse embryonic fibroblasts and a P19 EC cell clone [P19-36/12 (-) cells] lacking expression of caspase-12. Caspase-9 and caspase-8 deficiency inhibited and delayed the onset of DNA fragmentation but did not inhibit caspase-12 processing induced by ER stress. P19-36/12 (-) cells underwent apoptosis upon ER stress, with cytochrome c release and caspase-8 and caspase-9 activation. The dominant negative form of FADD and z-VAD-fmk inhibited caspase-8, caspase-9, Bid processing, cytochrome c release, and DNA fragmentation induced by ER stress, suggesting that caspase-8 and caspase-9 are the main caspases involved in ER stress-mediated apoptosis of P19-36/12 (-) cells. Caspase-8 deficiency also inhibited the cytochrome c release induced by ER stress. Thus, in parallel with the caspase-12 activation, ER stress triggers caspase-8 activation, resulting in cytochrome c/caspase-9 activation via Bid processing.

Ex vivo whole-embryo culture of caspase-8-deficient embryos normalize their aberrant phenotypes in the developing neural tube and heart.

Caspase-8 plays the role of initiator in the caspase cascade and is a key molecule in death receptor-induced apoptotic pathways. To investigate the physiological roles of caspase-8 in vivo, we have generated caspase-8-deficient mice by gene targeting. The first signs of abnormality in homozygous mutant embryos were observed in extraembryonic tissue, the yolk sac. By embryonic day (E) 10.5, the yolk sac vasculature had begun to form inappropriately, and subsequently the mutant embryos displayed a variety of defects in the developing heart and neural tube. As a result, all mutant embryos died at E11.5. Importantly, homozygous mutant neural and heart defects were rescued by ex vivo whole-embryo culture during E10.5-E11.5, suggesting that these defects are most likely secondary to a lack of physiological caspase-8 activity. Taken together, these results suggest that caspase-8 is indispensable for embryonic development.

The evolutionary conservation of the mammalian peroxidase genes.

Myeloperoxidase (MPO), eosinophil peroxidase (EPX) and lactoperoxidase (LPO) are mammalian peroxidase enzymes possessing similar structures and functions. Here, we demonstrate that the genes encoding these molecules form a cluster on mouse chromosome 11. Genomic sequence analysis revealed that the mouse LPO gene has similar genomic organization to the corresponding human gene. Our data strongly suggest the evolutionary conservation of mammalian peroxidase genes.

Estrogen decreases the responsiveness of subfornical organ neurons projecting to the hypothalamic paraventricular nucleus to angiotensin II in female rats.

Extracellular single-unit activity was recorded from subfornical organ (SFO) neurons antidromically identified as projecting to the hypothalamic paraventricular nucleus (PVN) in urethane-anesthetized ovariectomized female rats that were treated with either propylene glycol (PG) vehicle or estradiol benzoate (EB). No significant differences were observed between the PG- and EB-treated rats in the latency, conduction velocity, or threshold of antidromic activation. The mean spontaneous firing rate was significantly lower and the refractory period was significantly longer in the EB-treated rats. In the identified units that were activated by angiotensin II (ANG II) applied iontophoretically, the amount of excitatory response to intracarotid administration of ANG II was much greater in the PG-treated than in the EB-treated rats. These results suggest that estrogen may decrease the responsiveness of SFO neurons projecting to the PVN to circulating ANG II.

Activation of serotonergic pathways from the midbrain raphe system to the subfornical organ by hemorrhage in the rat.

The role of serotonergic neural pathways from the midbrain raphe nuclei to the subfornical organ (SFO) in the central regulation of cardiovascular function and body fluid balance was investigated in adult male rats under urethane anesthesia. Eleven neurons in the dorsal raphe nucleus (DR) were antidromically activated by electrical stimulation of the SFO. Of these neurons, 6 displayed an excitatory response following hemorrhage (10 ml/kg bwt) while the remaining 5 neurons were unresponsive. Ninety-four neurons in the SFO were tested for a response to electrical stimulation of the DR or hemorrhage. Electrical stimulation of the DR caused orthodromic excitation (19%) or inhibition (5%) of the activity of SFO neurons. In 14 of 18 SFO neurons that displayed the excitation to the stimulation of the DR, hemorrhage (30 to 50 mm Hg suppression in mean arterial pressure) produced an increase of their discharge, while the stimulus was without effect in the remaining neurons responsive to the stimulation of the DR. The effects of hemorrhage on serotonin (5-HT) release in the region of the SFO were examined using intracerebral microdialysis techniques. Hemorrhage significantly increased 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the region of the SFO. The present data suggest that the serotonergic pathways from the DR to the SFO may relay activation of the peripheral baroreceptors to SFO neurons which result in enhanced excitability, indicating the involvement of the pathways in the regulation of cardiovascular function.

Activation of the subfornical organ enhances extracellular noradrenaline concentrations in the hypothalamic paraventricular nucleus in the rat.

Experiments were carried out to investigate whether angiotensinergic efferent pathways from the subfornical organ (SFO) regulate the noradrenergic system in the region of the hypothalamic paraventricular nucleus (PVN). Intracerebral microdialysis techniques were utilized to quantify the extracellular content of noradrenaline (NA) in the PVN area. In urethane-anaesthetized male rats, electrical stimulation (5-20 Hz, 600 microA) of the SFO significantly increased the NA concentration in the region of the PVN, and the increase was significantly prevented by pretreatment with the angiotensin II (ANG II) antagonist saralasin (Sar, 5 microg), into the third ventricle (3V). Injections of ANG II (5 microg) into the 3V significantly enhanced NA release in the PVN area. These results suggest that the angiotensinergic pathways from the SFO to the PVN may act to enhance NA release in the region of the PVN.

Angiotensinergic and noradrenergic mechanisms in the hypothalamic paraventricular nucleus participate in the drinking response induced by activation of the subfornical organ in rats.

The present study was done to investigate the contribution of the hypothalamic paraventricular nucleus (PVN) to the drinking response caused by activation of the subfornical organ (SFO) following angiotensin II (ANG II) injections in the awake rat. Microinjection of ANG II into the SFO elicited the drinking response. Previous injections of either saralasin, an ANG II antagonist, or phentolamine, an alpha-adrenoceptor antagonist, bilaterally into the PVN resulted in the significant attenuation of the drinking response to ANG II. Similar injections of any of the beta-adrenoceptor antagonist timolol, the muscarinic antagonist atropine, or saline vehicle into the PVN had no significant effect on the drinking response. In an attempt to clarify the neural mechanisms in the PVN involved in the drinking response to ANG II injected into the SFO, the effect of microinjection of ANG II into the SFO on noradrenaline (NA) release in the PVN was examined using intracerebral microdialysis techniques. The injection of the ANG II, but not saline vehicle, significantly enhanced the NA release in the region of the PVN. These results indicate the involvement of both the angiotensinergic and alpha-adrenergic systems in the PVN in the drinking response caused by angiotensinergic activation of the SFO, and imply that the angiotensinergic projections from the SFO to the PVN may serve to increase NA release which results in mediating water intake.

GABAergic modulation of neurons in the nucleus of the solitary tract with ascending projections to the subfornical organ in the rat.

Twenty-five neurons in the region of the nucleus of the solitary tract (NTS) were antidromically activated by electrical stimulation of the subfornical organ (SFO) in male rats under urethane anesthesia. Microiontophoretically applied bicuculline, a gamma-aminobutyric acid (GABA)(A) antagonist, but not phaclofen, a GABA(B) antagonist, attenuated the post-antidromic inhibitory response evoked by SFO stimulation of approximately two-third (n=17) of identified neurons, indicating the existence of recurrent inhibitory systems through GABA(A) receptors. Iontophoretically applied GABA decreased the spontaneous activity of all identified neurons, and the GABA-induced inhibition was prevented by simultaneously applied bicuculline, but not by phaclofen. Activation of peripheral baroreceptors, achieved by rising arterial blood pressure with an intravenous infusions of phenylepherine, suppressed the activity of the majority (n=20) of identified neurons. The inhibitory response of identified neurons (n=7) to baroreceptor activation was partially antagonized by iontophoretically applied bicuculline, but not by phaclofen. These results imply that GABAergic mechanisms may modulate the baroreceptor reflex acting on GABA(A) receptors of NTS neurons with ascending projections to the SFO in the region of the NTS.

Intraosseous neurilemmoma of the mandible.

We report a rare case of intraosseous neurilemmoma of the mandible, with an emphasis on radiographic findings. The tumor, located mainly in the premolar region, presented as an expansive, unilocular, well-defined, radiolucent lesion on plain radiography. No dilatation of the mandibular canal was identified. MR imaging helped to identify the solid nature of the tumor. A biopsy was necessary to make the final diagnosis because of the relatively nonspecific nature of the lesion.

Identification and characterization of rat AILIM/ICOS, a novel T-cell costimulatory molecule, related to the CD28/CTLA4 family.

Activation-inducible lymphocyte immuno-mediatory molecule (AILIM) is an inducible cell surface glycoprotein expressed on thymocytes and activated lymphocytes. Specific monoclonal antibody to rat AILIM induced the cell aggregation of a rat thymoma cell line and ConA-activated splenocytes. In the present study, we identified the primary structure of two species of rat AILIM by expression cloning. We also cloned mouse and human AILIM homologues and the predicted amino acid sequences were identical to those of the inducible costimulator ICOS/CRP-1, which belongs to the CD28/CTLA4 family. Although the human and mouse AILIM/ICOS molecule is localized on T-cells, the major population of AILIM/ICOS-positive cells in rat splenocyte was CD45RA-positive B-cells. The expression level of AILIM/ICOS on T-cells was relatively low; however, its expression was drastically induced by the treatment with PMA plus Ca-ionophore or the engagement of CD3 and these costimulatory molecules. Almost all T-cells exhibited potency as to its expression. Functional analysis of AILIM/ICOS demonstrated that AILIM-mediated costimulation was relatively weak compared to that of human.