An analog-AI chip for energy-efficient speech recognition and transcription.

Models of artificial intelligence (AI) that have billions of parameters can achieve high accuracy across a range of tasks1,2, but they exacerbate the poor energy efficiency of conventional general-purpose processors, such as graphics processing units or central processing units. Analog in-memory computing (analog-AI)3-7 can provide better energy efficiency by performing matrix-vector multiplications in parallel on 'memory tiles'. However, analog-AI has yet to demonstrate software-equivalent (SWeq) accuracy on models that require many such tiles and efficient communication of neural-network activations between the tiles. Here we present an analog-AI chip that combines 35 million phase-change memory devices across 34 tiles, massively parallel inter-tile communication and analog, low-power peripheral circuitry that can achieve up to 12.4 tera-operations per second per watt (TOPS/W) chip-sustained performance. We demonstrate fully end-to-end SWeq accuracy for a small keyword-spotting network and near-SWeq accuracy on the much larger MLPerf8 recurrent neural-network transducer (RNNT), with more than 45 million weights mapped onto more than 140 million phase-change memory devices across five chips.

Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003).

BACKGROUND: This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC. PATIENTS AND METHODS: Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat. RESULTS: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively. CONCLUSION: Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).

Blood identification and discrimination between human and nonhuman blood using portable Raman spectroscopy.

Raman spectroscopy is commonly used in chemistry to identify molecular structure. This technique is a nondestructive analysis and needs no sample preparation. Recently, Raman spectroscopy has been shown to be effective as a multipurpose analytical method for forensic applications. In the present study, blood identification and discrimination between human and nonhuman blood were performed by a portable Raman spectrometer, which can be used at a crime scene. To identify the blood and to discriminate between human and nonhuman blood, Raman spectra of bloodstains from 11 species (human, rat, mouse, cow, horse, sheep, pig, rabbit, cat, dog, and chicken) were taken using a portable Raman spectrometer. Raman peaks for blood (742, 1001, 1123, 1247, 1341, 1368, 1446, 1576, and 1619 cm-1) could be observed by the portable Raman spectrometer in all 11 species, and the human bloodstain could be distinguished from the nonhuman ones by using a principal component analysis. This analysis can be performed on a bloodstain sample of at least 3 months old. The portable Raman spectrometer can be used at a crime scene, and this analysis is useful for forensic examination.

Community structure of denitrifying and total bacteria during nitrogen accumulation in an ammonia-loaded biofilter.

AIMS: To obtain insight into the complex behaviour of denitrifying and total bacterial groups during the nitrogen accumulation process in an ammonia-loaded biofiltration system. METHODS AND RESULTS: Denitrifying and total bacterial communities in a laboratory-scale rockwool biofilter with intermittent water recirculation were analysed by using denaturing gradient gel electrophoresis targeting nosZ and metabarcoding sequencing of the 16S rRNA gene. Gene abundance was evaluated by quantitative PCR. The nosZ number increased from 6·59 × 106 to 3·33 × 108 copies per gram dry sample over the 436 days of operation, during which nitrogen mass balance errors increased to 39%. The nosZ sequences associated with the genera Castellaniella, Hyphomicrobium and Pseudomonas were detected. Metabarcoding sequencing analysis indicated that the proportions of the genera for which at least one denitrifying strain or species possessing nosZ had been characterized corresponded well to the nitrogen loss. In addition, the genus Nitrosococcus (γ-proteobacteria) increased its relative abundance at days 317 and 436. CONCLUSIONS: The increased proportion of denitrifying bacteria in this ammonia-loaded biofiltration system could be related to the nitrogen loss. SIGNIFICANCE AND IMPACT OF THE STUDY: These results will help to clarify the complex behaviour of nitrifiers and denitrifiers within ammonia-loaded biofiltration systems.

Effects of new over-the-counter periodontal ointment-containing applicator with single-tuft brush on cytokine levels in gingival crevicular fluid during supportive periodontal therapy phase: a randomized double-blind clinical trial.

BACKGROUND AND OBJECTIVE: The biochemical effects of an over-the-counter (OTC) medication were studied, which consists of a single-tuft brush containing cetylpyridinium chloride as a bactericidal agent, dipotassium glycyrrhizate as an anti-inflammatory drug and allantoin as a promoter of cell proliferation and wound healing, for delivery to hardly brushed sites. MATERIAL AND METHODS: This randomized controlled double-blind study was performed in 61 subjects with chronic periodontitis in supportive periodontal therapy phase (test group: n = 27; placebo group: n = 28; dropout: n = 6). The OTC medication was self-applied twice a day for 12 wk to two molars with probing pocket depths of 4-6 mm. Biochemical indicators were evaluated at baseline and 12 wk using the suspension array system for eight cytokines and chemokines (interleukin [IL]-1ß, IL-1ra, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 and tumor necrosis factor [TNF]-α) in gingival crevicular fluid. RESULTS: The levels of IL-1ß, IL-6, IL-8 and TNF-α remained significantly lower in the test group compared to the placebo group. In the placebo group, when the probing pocket depth at baseline was 4 mm, IL-1ß increased, particularly in the second molar tooth, and the greatest increase was seen when PPD at baseline was 5-6 mm. In the test group, IL-1ß decreased markedly in cases with furcation involvement and low bleeding on probing at baseline. In both groups, IL-1ß, IL-6 and TNF-α were closely correlated with each other. CONCLUSION: This OTC medication is biochemically effective for steady chronic periodontitis in the supportive periodontal therapy phase.

Effects of low-intensity, elastic band resistance exercise combined with blood flow restriction on muscle activation.

We examined the effects of blood flow-restricted, low-intensity resistance exercise (termed kaatsu) using an elastic band for resistance on muscle activation. Nine men performed triceps extension and biceps flexion exercises (four sets respectively) using an elastic band for resistance with blood flow restriction (BFR) or CON (unrestricted blood flow). During a BFR session, subjects wore pressure cuffs inflated to 170-260 mmHg on the proximal region of both arms. Surface electromyography (EMG) was recorded from the triceps brachii and biceps brachii muscles, and mean integrated EMG (iEMG) was analyzed. Blood lactate concentration was obtained before (Pre) and immediately after two exercises (Post). During triceps extension and biceps flexion exercises, muscle activation increased progressively (P < 0.05) under BFR (46% and 69%, respectively) but not under CON (12% and 23%, respectively). Blood lactate concentration at Post was higher (P < 0.05) under BFR than under CON (3.6 and 2.1 mmol/L, respectively). Blood lactate concentration at Post was significantly correlated with increased iEMG in both triceps extension (r = 0.65, P < 0.01) and biceps flexion exercises (r = 0.52, P < 0.05). We conclude that kaatsu training using elastic bands for resistance enhances muscle activation and may be an effective method to promote muscle hypertrophy in older adults or patients with a low level of activity.

Muscle size and arterial stiffness after blood flow-restricted low-intensity resistance training in older adults.

Previous studies have shown that blood flow-restricted low-intensity resistance training (BFR-RT) causes muscle hypertrophy while maintaining arterial function in young adults. We examined the effects of BFR-RT on muscle size and arterial stiffness in older adults. Healthy subjects (ages 61-84 years) were divided into BFR-RT (n = 9) or non-training control (CON; n = 10) groups. The BFR-RT group performed 20% and 30%, respectively, of one-repetition maximal (1-RM) knee extension and leg press exercises, 2 days/wk for 12 weeks. The BFR-RT group wore elastic cuffs (120-270 mmHg) on both legs during training. Magnetic resonance imaging-measured muscle cross-sectional area (CSA), 1-RM strength, chair stand (CS) test, and cardio-ankle vascular index testing (CAVI), an index of arterial stiffness, were measured before and 3-5 days after the final training session. Muscle CSA of the quadriceps (8.0%), adductors (6.5%), and gluteus maximus (4.4%), leg extension and leg press 1-RM strength (26.1% and 33.4%), and CS performance (18.3%) improved (P < 0.05) in the BFR-RT group, but not in the CON group. In CAVI testing, there were no changes in both two groups. In conclusion, BFR-RT improves muscle CSA as well as maximal muscle strength, but does not negatively affect arterial stiffness or humeral coagulation factors in older adults.

Feasibility of a novel diagnostic chart of intramedullary spinal cord tumors in magnetic resonance imaging.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: Each type of intramedullary spinal cord tumor (IMSCT) has specific anatomical and pathological features visible on magnetic resonance (MR) imaging. The purpose of this study was to investigate the accuracy of preoperative IMSCT diagnosis using our diagnostic chart of tumor-specific MR imaging findings. SETTING: Hamamatsu, Japan. METHODS: From 2009 to 2013, 28 consecutive patients with IMSCT who underwent surgery in our university hospital were included in this study. There were 17 men and 11 women with an average age of 49 years (12-81). The pathological diagnoses were hemangioblastoma (12), ependymoma (11), astrocytoma (4) and squamous cell carcinoma (1). Tumor-specific MR imaging findings were as follows: ependymoma ((a) spinal cord swelling, (b) contrast effect with necrosis, (c) tumor in the center of the spinal cord), hemangioblastoma ((a) spinal cord swelling, (b) homogeneous contrast effect) and astrocytoma ((a) spinal cord swelling, (b) contrast effect is either, (c) eccentric tumor). Based on these features, we generated a diagnostic chart to investigate the MR imaging diagnosis accuracy for IMSCTs. RESULTS: The accuracy of preoperative diagnosis was 89% (25/28 cases). Correct diagnoses were made in 100% of hemangioblastomas (12/12 cases), 90% of ependymomas (9/11 cases) and 100% of astrocytomas (4/4 cases). CONCLUSIONS: Different types of IMSCTs exhibit unique MR imaging characteristics. These features can be used to preoperatively diagnose IMSCTs with high accuracy.

Responses of community structure of amoA-encoding archaea and ammonia-oxidizing bacteria in ammonia biofilter with rockwool mixtures to the gradual increases in ammonium and nitrate.

AIMS: To investigate community shifts of amoA-encoding archaea (AEA) and ammonia-oxidizing bacteria (AOB) in biofilter under nitrogen accumulation process. METHODS AND RESULTS: A laboratory-scale rockwool biofilter with an irrigated water circulation system was operated for 436 days with ammonia loading rates of 49-63 NH(3) g m(-3) day(-1). The AEA and AOB communities were investigated by denaturing gradient gel electrophoresis, sequencing and real-time PCR analysis based on amoA genes. The results indicated that changes in abundance and community compositions occurred in a different manner between archaeal and bacterial amoA during the operation. However, both microbial community structures mainly varied when free ammonia (FA) concentrations in circulation water were increasing, which caused a temporal decline in reactor performance. Dominant amoA sequences after this transition were related to Thaumarchaeotal Group I.1b, Nitrosomonas europaea lineages and one subcluster within Nitrosospira sp. cluster 3, for archaea and bacteria, respectively. CONCLUSIONS: The specific FA in circulation water seems to be the important factor, which relates to the AOB and AEA community shifts in the biofilter besides ammonium and pH. SIGNIFICANCE AND IMPACT OF THE STUDY: One of the key factors for regulating AEA and AOB communities was proposed that is useful for optimizing biofiltration technology.

The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.

Citrullinaemia (CTLN) is an autosomal recessive disease caused by deficiency of argininosuccinate synthetase (ASS). Adult-onset type II citrullinaemia (CTLN2) is characterized by a liver-specific ASS deficiency with no abnormalities in hepatic ASS mRNA or the gene ASS (refs 1-17). CTLN2 patients (1/100,000 in Japan) suffer from a disturbance of consciousness and coma, and most die with cerebral edema within a few years of onset. CTLN2 differs from classical citrullinaemia (CTLN1, OMIM 215700) in that CTLN1 is neonatal or infantile in onset, with ASS enzyme defects (in all tissues) arising due to mutations in ASS on chromosome 9q34 (refs 18-21). We collected 118 CTLN2 families, and localized the CTLN2 locus to chromosome 7q21.3 by homozygosity mapping analysis of individuals from 18 consanguineous unions. Using positional cloning we identified a novel gene, SLC25A13, and found five different DNA sequence alterations that account for mutations in all consanguineous patients examined. SLC25A13 encodes a 3.4-kb transcript expressed most abundantly in liver. The protein encoded by SLC25A13, named citrin, is bipartite in structure, containing a mitochondrial carrier motif and four EF-hand domains, suggesting it is a calcium-dependent mitochondrial solute transporter with a role in urea cycle function.

Histiocytic sarcoma of the palate: a case report.

Histiocytic sarcoma is a malignant proliferation of cells that exhibit morphological and immunophenotypic features of mature histiocytes. Owing to its rarity, its clinical features and standard treatment have not yet been established. This report describes a case of histiocytic sarcoma of the palate that developed in a 76-year-old man, the first report of an intraoral histiocytic sarcoma. An extended resection was performed; however, establishing the excision line was extremely difficult because assessing the tumour boundary on imaging was challenging and the tumour underwent dynamic gross morphological changes following biopsy. Complete resection is required to obtain a favourable prognosis for high-grade tumours with indistinct borders. In this case, an intraoperative rapid examination with frozen section analysis was performed along the planned excision line to completely resect the tumours exhibiting such behaviour. At 28 months postoperatively, the patient demonstrated no recurrence or metastasis; however, he is under careful monitoring.

Ten cases of gastro-tracheobronchial fistula: a serious complication after esophagectomy and reconstruction using posterior mediastinal gastric tube.

Gastro-tracheobronchial fistula (GTF) is a rare but life-threatening complication specifically observed after esophagectomy and reconstruction using posterior mediastinal gastric tube. Ten cases of GTF were encountered in three hospitals in 2000-2009. Their clinicopathological, surgical, and postoperative care are summarized, together with a review of previously reported cases. GTF was classified as anastomotic leakage (n= 5), gastric necrosis (n= 4), and gastric ulcer type (n= 1). The anastomotic leakage type appeared about 2 weeks (postoperative day [POD]: 8-35) after esophagectomy, was located in the cervical or higher thoracic trachea. Breathing and pneumonia were controlled by tracheal tube placed in the distal of fistula. The gastric necrosis type was noted in patients who developed necrosis of the upper part of the gastric tube and abscess formation behind the tracheal wall, at POD 20-36 around the carina, the site of pronounced ischemia. Due to the large fistula around the carina, emergency surgery with muscle patch repair was frequently required for the control of aspiration pneumonia. Patients of the gastric ulcer type had peptic ulcer in the lesser curvature of the gastric tube, which perforated into the right bronchus long after surgery (POD 630). With respect to tracheobronchial factors, preoperative chemoradiation (three cases) and pre-tracheal node dissection (three cases) tended to increase the risk of GTF. Closure of GTF by surgery (muscle patch repair) was successful in four cases and by nonsurgical treatment in three cases. In one case, stable oral intake was achieved by bypass operation without closure of GTF. Hospital death occurred in three cases. Understanding the pathogenesis and treatment options of GTF is important for surgeons who deal with esophageal cancer.

Movement strategies during car transfers in individuals with tetraplegia: a preliminary study.

STUDY DESIGN: Three-dimensional kinematic analysis of car transfer (CT) movement in four adult males with C6 tetraplegia. OBJECTIVES: The aim of the present study was to assess the normal transfer technique movement from a wheelchair to a car (that is, CT) in subjects with tetraplegia. A better understanding of CT movement is invaluable knowledge for spinal cord injury rehabilitation. This type of knowledge will improve rehabilitation programs so that patients with tetraplegia will have greater societal participation. SETTING: School of Comprehensive Rehabilitation, Osaka Prefecture University, Osaka, Japan. METHODS: Four adult males with C6 tetraplegia, an impairment grade of A according to the American Spinal Injury Association guidelines, took part in the study. The subjects used their own wheelchair and car in our assessments of their CT movement technique. Movements were assessed using a three-dimensional video analysis system with six digital video cameras. CT data, which included lateral displacement of the head and buttocks, and angular displacement of neck flexion and trunk forward inclination, were collected and correlation coefficients were calculated. RESULTS: All four subjects demonstrated negative correlations in lateral displacements greater than 0.70. As for correlation coefficients of angular displacement, two subjects demonstrated negative correlations (r = -0.98 and r = -0.77) and one subject demonstrated a positive correlation (r = 0.75). The neck flexion and trunk forward inclination strategy was different among the four subjects. CONCLUSIONS: Each subject with C6 tetraplegia demonstrated different strategies during CT movement.

A prospective dose-finding trial using a modified continual reassessment method for optimization of fludarabine plus melphalan conditioning for marrow transplantation from unrelated donors in patients with hematopoietic malignancies.

BACKGROUND: Because of the less graft-facilitating effect by bone marrow (BM), we need to assess a dosage of conditioning more accurately particularly in combination with reduced-intensity conditioning. Thus we examined that modified continual reassessment method (mCRM) is applicable for deciding appropriate conditioning of allogeneic BM transplantation. PATIENTS AND METHODS: The conditioning regimen consisted of i.v. fludarabine (125 mg/m2) plus an examination dose of i.v. melphalan. The primary endpoint was a donor-type T-cell chimerism at day 28 with successful engraftment defined as >90% donor cells. Five patients per dose level were planned to be accrued and chimerism data were used to determine the next dose. RESULTS: Seventeen patients were enrolled at doses between 130 and 160 mg/m2. The dose was changed from 160 to 130 mg/m(2) (second level) after five full-donor chimerisms. With one patient of 0% chimera in the second level, the dose was increased to 135 mg/m2 (third level). Following five full-donor chimerisms in the third level, the study was complete as projected. CONCLUSIONS: mCRM was shown to be a relevant method for dose-finding of conditioning regimen. The melphalan dose of 135 mg/m2 was determined as the recommended phase II dose to induce initial full-donor chimerism.

Bacterial community dynamics in aerated cow manure slurry at different aeration intensities.

AIMS: This study aimed to characterize microbial community dynamics in aerated cow manure slurry at different aeration intensities. METHODS AND RESULTS: Batch aerobic treatments were set up in 5-l jar fermentor, each containing 3 l of manure slurry; the slurries were subjected to low, medium and high (50, 150 and 250 ml min(-1), respectively) aeration for 9 days. Microbial community composition was determined using terminal restriction fragment length polymorphism and a clone library targeting 16S rRNA genes. High and medium aeration accelerated organic carbon degradation in parallel with the degree of aeration intensity; however, 90% of the initial total organic carbon was retained during low-aeration treatment. During the active stages of organic carbon decomposition, clones belonging to the class Bacilli accumulated. Moreover, Bacilli accumulation occurred earlier under high aeration than under medium aeration. CONCLUSIONS: Organic matter degradation was mainly governed by a common microbial assemblage consisting of many lineages belonging to the class Bacilli. The timing of community development differed depending on aeration intensity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports on changes in several environmentally important parameters and the principal microbial assemblage during the pollution-reducing phase of cattle manure aeration treatment.

Impact of intraperitoneal chemotherapy after gastrectomy with positive cytological findings in peritoneal washings.

BACKGROUND: There is no standard treatment available for gastric cancer patients whose sole 'non-curative factor' is positivecytological findings in peritoneal washings (CFPW). The aim of this study was to examine the safety, pharmacokinetics and efficacy for free intraperitoneal cancer cells of intraperitoneal chemotherapy with paclitaxel after gastrectomy with en bloc D2 lymph node dissection in cases of gastric cancer with positive CFPW. METHODS: Ten patients with gastric cancer who underwent gastrectomy and systemic lymphadenectomy with D2 dissection, without any other non-curative factors besides positive CFPW, were treated with early postoperative intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complications were measured using NCI-CTC version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatographic assay. RESULTS: Grade 3/4 toxic effects included anemia (20%) and neutropenia (10%) that required no treatment. Operative complications were, for example, superficial surgical site infections (10%) that were treated with antibiotics. No viable cancer cells were observed in the intra-abdominal fluid 24 h after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve ratio was 2,003.3:1. CONCLUSION: Intraperitoneal chemotherapy with paclitaxel is a safe and effective treatment modality for free intraperitoneal cancer cells.

Anticardiolipin antibodies recognize beta 2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface.

Anticardiolipin antibodies (aCL) derived from the sera of individuals exhibiting the antiphospholipid syndrome (APS) directly bind to beta 2-glycoprotein I (beta 2-GPI), which is adsorbed to an oxidized polystyrene surface. Oxygen atoms were introduced on a polystyrene surface by irradiation with electron or gamma-ray radiation. X-ray photoelectron spectroscopy revealed the irradiated surfaces were oxidized to generate C-O and C = O moieties. aCL derived from either APS patients or (NZW x BXSB)F1 mice bound to beta 2-GPI coated on the irradiated plates, depending on the radiation dose. Antibody binding to beta 2-GPI on the irradiated plates was competitively inhibited by simultaneous addition of cardiolipin (CL)-coated latex beads mixed together with beta 2-GPI but were unaffected by addition of excess beta 2-GPI, CL micelles, or CL-coated latex beads alone. There was a high correlation between binding values of aCL in sera from 40 APS patients obtained by the anti-beta 2-GPI enzyme-linked immunosorbent assay (ELISA) using the irradiated plates and those by the beta 2-GPI-dependent aCL ELISA. Therefore, aCL have specificity for an epitope on beta 2-GPI. This epitope is expressed by a conformational change occurring when beta 2-GPI interacts with an oxygen-substituted solid phase surface.

Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding.

Accumulating evidence indicates that the Cbl protein plays a negative role in immune receptor signaling; however, the mode of Cbl action in B cell receptor (BCR) signaling still remains unclear. DT40 B cells deficient in Cbl showed enhanced BCR-mediated phospholipase C (PLC)-gamma2 activation, thereby leading to increased apoptosis. A possible explanation for the involvement of Cbl in PLC-gamma2 activation was provided by findings that Cbl interacts via its Src homology 2 (SH2) domain with B cell linker protein (BLNK) after BCR ligation. BLNK is a critical adaptor molecule for PLC-gamma2 tyrosine phosphorylation through its binding to the PLC-gamma2 SH2 domains. As a consequence of the interaction between Cbl and BLNK, the BCR-induced recruitment of PLC-gamma2 to BLNK and the subsequent PLC-gamma2 tyrosine phosphorylation were inhibited. Thus, our data suggest that Cbl negatively regulates the PLC-gamma2 pathway by inhibiting the association of PLC-gamma2 with BLNK.

Identification of a unique antigen peptide pRL1 on BALB/c RL male 1 leukemia recognized by cytotoxic T lymphocytes and its relation to the Akt oncogene.

BALB/c radiation leukemia RL male 1 is an immunogenic tumor. We established bulk and cloned cytotoxic T lymphocyte (CTL) lines from regressor (BALB/c x C57BL/6)F1 (CB6F1) spleen cells that recognized RL male 1 specifically. We then obtained antigen peptide recognized by CTL from RL male 1 by acid extraction. Analysis of the acid extract by reversed-phase high performance liquid chromatography (HPLC) on a semipreparative C18 column revealed that fractions eluted in 23 min (peak a) and 26 min (peak b) showed sensitization activity on the P815 target for specific CTL. On further purification of these fractions by HPLC and direct sequencing by Edman degradation, we identified the CTL-recognizing RL male 1 peptide pRL1a (IPGLPLSL) in peak a and its possible precursor peptide pRL1b (SIIPGLPLSL) in peak b. Sequence homology indicated that these peptides were derived from the 5' untranslated region of c-akt oncogene.

Significant expression of interleukin 15 in rat experimental severe acute pancreatitis.

PURPOSE: In severe acute pancreatitis (SAP), multiple organ dysfunction syndrome is a contributor to high mortality. We recently demonstrated that the serum interleukin (IL)-15 level is a predictor of the complications and mortality in clinical SAP. The aim was to investigate the role of IL-15 in experimental SAP. MATERIALS AND METHODS: SAP was induced by retrograde injection of 3 and 20% sodium deoxycholate (DCA) into biliopancreatic ducts in rats (DCA pancreatitis). Expressions of IL-15 were evaluated by Western blotting and immunohistochemical staining. Recombinant IL-15 protein was administered intraperitoneally, and the effects were investigated. RESULTS: Western blotting revealed the expressions of IL-15 in the pancreas, liver, lung and intestine in 3% DCA pancreatitis. Immunohistochemical staining showed the expression of IL-15 in the cytoplasm of each organ. In 3% DCA pancreatitis, administration of recombinant IL-15 protein attenuated the elevation of serum alanine aminotransferase (ALT) levels and improved the morphological change of the lung 18 h after the induction of SAP. Moreover, in 20% DCA pancreatitis, IL-15 improved the elevation of serum amylase and ALT levels 6 h after the induction. CONCLUSIONS: These results suggest that IL-15 is related to organ dysfunction during SAP, and that IL-15 functions as a protective factor against the organ injuries.