Pulse chirp enhances the laser acceleration of neutral particles.

Accelerating neutral atoms is challenging because such particles are not directly manipulated by electric and magnetic fields as charged particles. In our acceleration scheme, the excited atom requires a sufficiently high gradient acceleration force. The key challenge in laser acceleration experiments is that not only must the photon energy excite atoms to the Rydberg state, but also atoms must not be ionized in an intense laser field. In this Letter, we propose using a chirped laser pulse to achieve the objectives above. The enhancement effect of the pulse chirp on the laser acceleration of neutral particles is investigated via numerical simulation and analytical analysis.

Neutral particles pushed or pulled by laser pulses: erratum.

We present an erratum to our Letter [Opt. Lett.41, 230 (2016)10.1364/OL.41.000230]. This erratum corrects three typing errors. The corrections have no influence on the results and conclusions of the original Letter.

Direct observation of muonium reacting with uncapped gold nanoparticles in porous silica and nature of the final state.

We report the reaction of muonium (Mu = [µ+e-]), a light isotopic analog of hydrogen, with uncapped gold nanoparticles embedded in mesoporous silica. Using the radio-frequency muon spin rotation (RF-µSR) technique, we directly observe and characterize the resulting final state on the nanoparticle surface, showing conclusively its diamagnetic nature. The magnetic environment experienced by the reacted muons is only weakly perturbed compared to that of muons in a silica reference, consistent with the surface of the gold nanoparticles being metallic and non-magnetic. We demonstrate the potential of RF-µSR for the investigation of the surface properties of nanoparticles and show the feasibility of Knight shift measurements of muons on metal surfaces.

[Study on the value of serum des-γ-carboxy prothrombin in predicting hepatocellular carcinoma recurrence after liver transplantation].

Objective: To explore the clinical value of serum des-γ-carboxy prothrombin (DCP) in predicting hepatocellular carcinoma recurrence after liver transplantation. Methods: A total of 115 cases with hepatocellular carcinoma who underwent liver transplantation in Zhongshan Hospital Affiliated to Fudan University from October 2016 to December 2018 were retrospectively analyzed. Receiver operating characteristic curve analysis, Mann-Whitney U test, Kaplan-Meier method, Log-Rank test, χ2 test, univariate and multivariate Cox regression analysis and other statistical methods were used to explore the value of DCP in predicting tumor recurrence after liver transplantation and its correlation with clinicopathological characteristics. Results: The preoperative serum DCP level in recurrent population after liver transplantation was significantly higher than that in non-recurrent population (P < 0.001). The optimal cut-off value of preoperative DCP for predicting recurrence was 200mAU/ml with the use of receiver operating characteristic curve. The sensitivity, specificity, Youden's index and the receiver operating characteristic curve was 87.90%, 57.30%, 0.452, and 0.726, respectively. Survival analysis results grouped by this cut-off value showed that patients with preoperative DCP ≥200mAU/ml had a higher probability of recurrence (P < 0.001). Further, subgroup survival analysis showed that patients with preoperative DCP≥200 mAU/ ml had a higher probability of recurrence than other cases of alpha-fetoprotein negative subgroup, cumulative tumor diameter ≤ 9 cm subgroup and Milan criteria subgroup (P < 0.05). Cox regression analysis showed that preoperative DCP≥200 mAU/ ml (P = 0.017) and cumulative tumor diameter > 9 cm (P = 0.014) was an independent risk factor for recurrence after liver transplantation. χ (2) test results showed that preoperative serum DCP level was correlated with gender, serum gamma glutamyltransferase level, serum alpha fetoprotein level, cumulative tumor diameter, vascular invasion, tumor differentiation and liver cancer transplant criteria (P < 0.05). Conclusion: Preoperative serum DCP can be used as a supplement to the existing liver cancer transplant criteria to predict hepatocellular carcinoma recurrence after liver transplantation. In addition, the accurate screening of patients with low risk of HCC recurrence after liver transplantation can improve the prognosis and efficacy of liver transplant patients.

[Overexpression of protein phosphatase 2 regulatory subunit B''α gene effect on proliferation and invasion of hepatoma cells].

Objective: To study the overexpression of protein phosphatase 2 regulatory subunit B''α gene effects on the proliferation and invasion of hepatoma cells. Methods: Immunohistochemistry method was used to analyze the expression of PPP2R3A in cancerous and paracancerous tissues. Hepatocellular carcinoma cell lines (Huh-7 and HepG2) with stably overexpressing PPP2R3A were constructed by lentiviral vector. Biological behavioral transition in hepatocellular carcinoma cell proliferation, cell cycle, apoptosis, invasion and metastasis were detected by cell counting kit-8 assay (CCK-8), flow cytometry, and transwell assay. A subcutaneous nude tumor mice model was constructed to validate the growth of hepatoma cells. Two independent sample t-tests were used to compare the groups. Results: The expression of PPP2R3A gene in human hepatocarcinoma tissues was higher than paracancerous tissues. The absorbance (A value) of hepatoma cells was increased (P < 0.05) after overexpression of PPP2R3A gene. The transition from G1-to-S phase was significantly increased i.e., the G1 phase of the cell cycle was reduced (Huh-7: t = 3.04, P = 0.0384; HepG2: t = 4.06, P = 0.0153), while the S phase was increased (Huh-7: t = 3.47, P = 0.0255; HepG2: t = 4.46, P = 0.0112). Early apoptotic rate was decreased (Huh-7: t = 7.34, P = 0.0018; HepG2: t = 4.06, P = 0.0153). The number of Huh-7 cells migrating to the lower chamber was increased (t = 3.18, P = 0.0334), and after the use of matrigel the number of cells reaching to the lower chamber was also increased (t = 2.84, P = 0.0464). The results of animal experiments showed that the subcutaneous tumor growth (t = 4.31, P = 0.0035) was significantly overexpressed in nude mice group. The results of Western blot showed that the expression of PARP and P53 protein in the spliced ​​forms decreased, while the accumulation of ß-catenin protein in the liver cancer cells was increased. Conclusion: Overexpressed PPP2R3A gene may promote proliferation, migration and invasion ability, inhibit apoptosis, induce G1/S phase transition, and participate in the biological behavior of hepatoma cells.

A new MICA allele, MICA*007:07, characterized by cloning and sequencing.

A new MICA allelic variant, MICA*007:07, was identified in an individual of Mongol ethnicity in the Inner Mongolia Autonomous Region, northern China. Following polymerase chain reaction-sequence-based typing (PCR-SBT), this new allele was further confirmed by cloning and sequencing. MICA*007:07 differs from MICA*007:01 by a synonymous mutation from G to A at the 2nd nucleotide position in exon 2. MICA*007:07 was linked to HLA-B*27:05.

Neutral particles pushed or pulled by laser pulses.

Acceleration of neutral particles is of great importance in many areas, such as controlled chemical reactions, atomic nanofabrication, and atom optics. Recent experimental studies have shown that pulsed lasers can be used to push neutral Rydberg atoms forward [Nature 461, 1261 (2009)10.1038/nature08481; Nat. Photonics 6, 386 (2012)10.1038/nphoton.2012.87]. Our simulation shows that pulsed lasers can also be used to pull Rydberg atoms back toward a light source. In particular, we proposed a method of using two laser pulses on a neutral atom, then selective operations on the neutral atom (pushing or pulling) can be performed by adjusting the delay time between the two laser pulses.

Communication: Chemisorption of muonium on gold nanoparticles: A sensitive new probe of surface magnetism and reactivity.

Chemisorption of muonium onto the surface of gold nanoparticles has been observed. Muonium (µ+e-), a light hydrogen-like atom, reacts chemically with uncapped 7 nm gold nanoparticles embedded in mesoporous silica (SBA-15) with a strong temperature-dependent rate. The addition rate is fast enough to allow coherent spin transfer into a diamagnetic muon state on the nanoparticle surface. The muon is well established as a sensitive probe of static or slowly fluctuating magnetic fields in bulk matter. These results represent the first muon spin rotation signal on a nanoparticle surface or any metallic surface. Only weak magnetic effects are seen on the surface of these Au nanoparticles consistent with Pauli paramagnetism.

Biochip analysis of prostate cancer.

Microarray expression analysis was used to forecast the roles of differentially co-expressed genes (DCG) and DCG and links in the pathogenesis of prostate cancer. In addition, we demonstrate that the relationship between transcriptional factors (TFs) and their targets can be considered a key factor in determining the difference between primary and metastatic prostate cancer. Regulatory impact factors were adopted to calculate the impact of TF. We identified 5 TFs and 29 target genes important in the transition between normal prostate and primary prostate cancer and 2 TFs and 7 target genes important in the transition between primary and metastatic prostate cancer. These results suggest that it may be possible to predict the clinical behavior of prostate cancer based on gene expression analysis.

Screening of feature genes of the renal cell carcinoma with DNA microarray.

AIM: To investigate the underlying molecular mechanisms of renal cell carcinoma (RCC) by using the microarray expression profiles of normal kidney and RCC tissue for early diagnosis and treatment of RCC. MATERIALS AND METHODS: The gene expression profile of GES781 was downloaded from Gene Expression Omnibus database, including including nine tissue samples of RCC tissues removed from nine patients and eight adjacent normal renal tissue samples. We identified the differentially expressed genes (DEGs) by Multtest package in R software. The screened DEGs were further analyzed by bioinformatics methods. Firstly, the comparison of the DEGs expression degree was performed by cluster analysis. Secondly, DAVID was used to perform functional analysis of up- and down- regulated genes and the protein-protein interaction (PPI) networks were constructed by prePPI. Finally, the pathways of genes in PPI networks were discovered by WebGestalt. RESULTS: Compared with the control, we screened 648 down-regulated and 681 up-regulated DEGs. And the down- and up-regulated DEGs with maximum expression degree were UMOD (uromodulin) and FABP7 (fatty acid binding protein 7), respectively. There was significant difference in the gene expression between the normal kidney and RCC tissue. The up-regulated DEGs in RCC tissue were significantly related to the immune responses and the down-regulated DEGs were significantly related to the oxidation reduction. The most significant pathway in the PPI network of UMOD was cytokine-cytokine receptor interaction. CONCLUSIONS: The screened DEGs have the potential to become candidate target molecules to monitor, diagnose and treat the RCC, and might be beneficial for the early diagnosis and medication control of RCC.

Retrospective study on 696 cases of traumatic dental injuries of primary dentition in Xi'an, China.

AIM: The aim of the present study was to explore the epidemiological characteristics and treatment of traumatic dental injuries of primary dentition (TDI-p) in Xi'an, China. MATERIALS: Data of children with TDI-p admitted between January 2018 and December 2019 at the Department of Pediatric Dentistry, Xi'an Jiaotong University Stomatology Hospital were retrospectively analysed. The epidemiological distribution characteristics and related treatment information of TDI-p were described. CONCLUSION: Compared with permanent dentition, TDI-p has its particularities, such as type of trauma, treatment procedure, and behavioural management. More attention should be paid to TDI-p by both dentists and guardians.

[Influence of visceral lipids obesity on the early postoperative complications after radical gastrectomy].

Objective: To investigate the effect of visceral fat area (VFA) on the surgical efficacy and early postoperative complications of radical gastrectomy for gastric cancer. Methods: A retrospective cohort study method was used. Clinicopathological data and preoperative imaging data of 195 patients who underwent D2 radical gastric cancer surgery at the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to December 2017 were analyzed retrospectively. Inclusion criteria: (1) complete clinicopathological and imaging data; (2) malignant gastric tumor diagnosed by preoperative pathology, and gastric cancer confirmed by postoperative pathology; (3) no preoperative complications such as bleeding, obstruction or perforation, and no distant metastasis. Those who had a history of abdominal surgery, concurrent malignant tumors, poor basic conditions, emergency surgery, palliative resection, and preoperative neoadjuvant therapy were excluded. The VFA was calculated by software and VFA ≥ 100 cm2 was defined as visceral obesity according to the Japan Obesity Association criteria . The patients were divided into high VFA (VFA-H, VFA≥100 cm2, n=96) group and low VFA (VFA-L, VFA<100 cm2, n=99) group . The clinicopathological characteristics, surgical outcomes and early postoperative complications were compared between the two groups. Univariate and multivariate Logistic regression models were used to analyze the risk factors of early complications. Receiver operating characteristic (ROC) curve was used to analyze predictive values of VFA for early complications. Pearson's χ2 test was used to analyze the correlation between BMI and VFA. Results: There were no significant differences in terms of gender, age, American Society of Anesthesiologists physical status classification, preoperative comorbidities, preoperative anemia, tumor TNM staging, N staging, T staging and tumor differentiation, surgical method, extent of resection, and tumor location between the VFA-L group and the VFA-H group (all P>0.05). However, patients in the VFA-H group had higher BMI, larger tumor, lower rate of hypoalbuminemia and greater subcutaneous fat area (SFA) (all P<0.05). The VFA-H group presented significantly longer operation time and significantly less number of harvested lymph nodes as compared to the VFA-L group (both P<0.05). However, there were no significant differences in intraoperative blood loss, conversion to laparotomy and postoperative hospital stay (all P>0.05). Complications of Clavien-Dindo grade II and above within 30 days after operation were mainly anastomosis-related complications (leakage, bleeding, infection and stricture), intestinal obstruction and incision infection. The VFA-H group had a higher morbidity of early complications compared to the VFA-L group [24.0% (23/96) vs 10.1% (10/99), χ2=6.657, P=0.010], and the rates of anastomotic complications and incision infection were also higher in the VFA group [10.4% (10/96) vs. 3.0% (3/99), χ2=4.274, P=0.039; 7.3% (7/96) vs. 1.0% (1/99), P=0.033]. Multivariate logistic analysis showed that high BMI (OR=3.688, 95%CI: 1.685-8.072, P=0.001) and high VFA (OR=2.526, 95%CI: 1.148-5.559,P=0.021) were independent risk factors for early complications. The area under the ROC curve (AUC) of VFA for predicting early complications was 0.645, which was higher than that of body weight (0.591), BMI (0.624) and SFA (0.626). Correlation analysis indicated that there was a significantly positive correlation between BMI and VFA (r=0.640, P<0.001). Conclusion: VFA ≥ 100 cm2 is an independent risk factor for early complications after radical gastrectomy for gastric cancer.It can better predict the occurrence of above early postoperative complications.

[Efficacy of laparoscopic proximal gastrectomy with double-tract reconstruction versus laparoscopic total gastrectomy with Roux-en-Y reconstruction for early upper gastric cancer].

Objective: To compare clinical efficacy between laparoscopic radical proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic radical total gastrectomy with Roux-en-Y reconstruction (LTG-RY) in patients with early upper gastric cancer, and to provide a reference for the selection of surgical methods in early upper gastric cancer. Methods: A retrospective cohort study method was carried out. Clinical data of 80 patients with early upper gastric cancer who underwent LPG-DTR or LTG-RY by the same surgical team at the Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into the DTR group (32 cases) and R-Y group (48 cases) according to surgical procedures and digestive tract reconstruction methods. Surgical and pathological characteristics, postoperative complications (short-term complications within 30 days after surgery and long-term complications after postoperative 30 days), survival time and nutritinal status were compared between the two groups. For nutritional status, reduction rate was used to represent the changes in total protein, albumin, total cholesterol, body mass, hemoglobin and vitamin B12 levels at postoperative 1-year and 2-year. Non-normally distributed continuous data were presented as median (interquartile range), and the Mann-Whitney U test was used for comparison between groups. The χ(2) test or Fisher's exact test was used for comparison of data between groups. The Mann-Whitney U test was used to compare the ranked data between groups. The survival rate was calculated by Kaplan-Meier method categorical, and compared by using the log-rank test. Results: There were no statistically significant differences in baseline data betweeen the two groups, except that patients in the R-Y group were oldere and had larger tumor. Patients of both groups successfully completed the operation without conversion to laparotomy, combined organ resection, or perioperative death. There were no significant differences in the distance from proximal resection margin to superior margin of tumor, postoperative hospital stay, time to flatus and food-taking, hospitalization cost, short- and long-term complications between the two groups (all P>0.05). Compared with the R-Y group, the DTR group had shorter distal margins [(3.2±0.5) cm vs. (11.7±2.0) cm, t=-23.033, P<0.001], longer surgery time [232.5 (63.7) minutes vs. 185.0 (63.0) minutes, Z=-3.238, P=0.001], longer anastomosis time [62.5 (17.5) minutes vs. 40.0 (10.0) minutes, Z=-6.321, P<0.001], less intraoperative blood loss [(138.1±51.6) ml vs. (184.3±62.1) ml, t=-3.477, P=0.001], with significant differences (all P<0.05). The median follow-up of the whole group was 18 months, and the 2-year cancer-specific survival rate was 97.5%, with 100% in the DTR group and 95.8% in the R-Y group (P=0.373). Compared with R-Y group at postoperative 1 year, the reduction rate of weight, hemoglobin and vitamin B12 were lower in DTR group with significant differences (all P<0.05); at postoperative 2-year, the reduction rate of vitamin B12 was still lower with significant differences (P<0.001), but the reduction rates of total protein, albumin, total cholesterol, body weight and hemoglobin were similar between the two groups (all P>0.05). Conclusions: LPG-DTR is safe and feasible in the treatment of early upper gastric cancer. The short-term postoperative nutritional status and long-term vitamin B12 levels of patients undergoing LPG-DTR are superior to those undergoing LTG-RY.

Simulations of vacuum laser acceleration: hidden errors from particle's initial positions.

Simulation of vacuum laser acceleration, because of its scheme's simplicity, attracts many people involved in. However, how to put the particle in the initial positions in the field has not been considered seriously in some such schemes. An inattentive choice of electron's initial conditions may lead to misleading results. Here we show that arbitrarily placing the particle within the laser field leads to an overestimation of its energy gain, and offer suggestions for selecting appropriate initial conditions.

Vacuum electron acceleration and bunch compression by a flat-top laser beam.

The field intensity distribution and phase velocity characteristics of a flat-top laser beam are analyzed and discussed. The dynamics of electron acceleration in this kind of beam are investigated using three-dimensional test particle simulations. Compared with the standard (i.e., TEM(00) mode) Gaussian beam, a flat-top laser beam has a stronger longitudinal electric field and a larger diffraction angle. These characteristics make it easier for electrons to be trapped and accelerated by the beam. With a flat-top shape, the laser beam is also applicable to the acceleration of low energy electron and bunch compression.

The Unhealthy Lifestyle Factors Associated with an Increased Risk of Poor Nutrition among the Elderly Population in China.

OBJECTIVES: The associations between nutritional status and lifestyle factors have not been well established. This study aimed to investigate the prevalence of poor nutrition and to examine the relationships between nutritional status and unhealthy lifestyle and other related factors among the elderly. METHODS: This cross-sectional study was conducted in Liaobu Town, Dongguan city, China. A total of 708 community-dwelling older adults aged ≥60 years were recruited by stratified random sampling. Data on sociodemographic characteristics, health and lifestyle factors, and the Mini Nutritional Assessment (MNA) scores were collected using structured questionnaires via face-to-face interviews. A multivariate logistic regression model was constructed to identify the risk factors of poor nutrition. RESULTS: The prevalence of malnutrition among the elderly adults in this study was 1.3%, and 24.4% were at risk of malnutrition (RM). Poor nutrition was significantly associated with female gender, older age, lower education, a high number of self-reported chronic diseases, and hospitalization in the last year. Unhealthy lifestyle factors associated with poor nutrition included current smoking status, higher alcohol consumption, lack of physical activity, longer duration of sitting, negative attitude towards life, and a poor family relationship. CONCLUSIONS: While the prevalence of malnutrition was low, RM was high in the elderly population in China. The determinants of malnutrition were explored and the relationships between nutritional status and unhealthy lifestyle factors were examined. The results of this study provide information for future longitudinal studies with multi-factorial interventional design in order to determine the effects of the causal relationships.

Effect of sinomenine on gene expression of the IL-1 beta-activated human synovial sarcoma.

Sinomenine is an alkaloid with pharmacological effects of anti-inflammation, anti-angiogenesis, anti-arthritis and immunosuppression. This study aimed to investigate the effect of sinomenine on gene expression of human synovial sarcoma cells (Hs701.T) activated by IL-1 beta. The proliferative effect of sinomenine was examined in the presence or absence of IL-1 beta by the [3H]-thymidine incorporation and MTT assay, respectively. Using DNA microarray technology and RT-PCR, the activating action of IL-1 beta and modulatory effect of sinomenine on Hs701.T were simultaneously determined. Results showed that IL-1 beta could stimulate the proliferation and gene expression of Hs701.T cells. Sinomenine could significantly inhibit proliferation of IL-1 beta-activated Hs701.T cells and suppress expression of 17 genes including IL-6, PlGF, Daxx, and HSP27. These genes were found to be important in tumor progression through the mediation of inflammation, cell adhesion, proliferation, apoptosis and angiogenesis. In conclusion, our study provides supplementary information for the further studies on the pharmacological effects of sinomenine acting on synovial sarcoma.

Protein expression in dairy cows with and without subclinical hypocalcaemia.

AIM: To determine differences in plasma proteomic profiles between healthy cows and those with subclinical hypocalcaemia within 12 hours after calving, and thereby explore the underlying biological mechanism of subclinical hypocalcaemia in dairy cows. METHODS: Plasma samples were collected within 6 hours of calving from Holstein cows on a farm in Heilongjiang, China; 32 with subclinical hypocalcaemia (plasma calcium concentration 1.38-2.00 mmol/L and no clinical signs) and 59 control cows (plasma calcium concentration 2.10-2.8 mmol/L). Plasma samples were applied to weak cationic exchange protein chips for protein profiling by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS), and the data were analysed using the PBS-IIC system. The amplitude of peaks for the two groups were compared using the Wilcoxon sum-rank test, and the mass-to-charge ratio of the peaks that differed was used to identify peptide fragments using the Swiss-Prot protein database. RESULTS: Seven peaks were identified in the subclinical hypocalcaemia group that differed from those of the control group (p<0.001), that represented six unique proteins. Expression of serum albumin, fibrinogen alpha chain, amyloid beta A4 proteins and neurosecretory protein VGF were increased, and expression of apolipoprotein A-II and serum amyloid A proteins were decreased in the subclinical hypocalcaemic cows compared with control cows. CONCLUSION: Use of SELDI-TOF-MS technology can effectively identify differences in plasma protein expression patterns in cows with subclinical hypocalcaemia. Neurosecretory protein VGF and amyloid beta A4 protein might represent useful biomarkers for diagnosis of subclinical hypocalcaemia.

Preclinical studies of allograft tolerance in rhesus monkeys: a novel anti-CD3-immunotoxin given peritransplant with donor bone marrow induces operational tolerance to kidney allografts.

A major challenge in clinical transplantation today is to design a practical and effective protocol for tolerance induction compatible with cadaver organ transplantation. A preclinical rhesus monkey kidney allograft model using immediate peritransplant anti-CD3 immunotoxin (anti-CD3-IT) and donor bone marrow (DBM) is shown here to induce operational tolerance with prolonged graft survival in the absence of chronic immunosuppressive drugs. Bone marrow harvested from the kidney donor was depleted of mature alloantigen-presenting cells and T cells by removing DR(bright) cells and CD3(bright) cells, respectively. In outbred, major histocompatibility complex-incompatible donor-recipient pairs with high pretransplant mixed lymphocyte response and cytotoxic T lymphocyte precursor activity, four of six allografts survived for periods of 120 days to >1.5 years. Graft acceptance after peritransplant treatment followed robust elimination of both peripheral blood T cells and lymph node T cells. In most recipients given anti-CD3-IT and DBM infusion, anti-donor immunoglobulin G responses were completely inhibited. Microchimerism was observed in all recipients studied, including those not given DBM, but levels of microchimerism did not correlate with graft survival. Anti-CD3-IT induction in combination with modified DBM protocols such as the depletion of mature T cells and DR(bright) antigen-presenting cells may offer new opportunities to improve clinical tolerance protocols beyond those attempted in the clinic to date. Overall, these results with anti-CD3-IT show promise for development of cadaver transplant tolerance induction.

Peritransplant tolerance induction with anti-CD3-immunotoxin: a matter of proinflammatory cytokine control.

BACKGROUND: Tolerance is gaining momentum as an approach to reduce lifelong immunosuppressive therapy while improving transplant longevity. Anti-CD3 immunotoxin (IT), FN18-CRM9, has potential to induce tolerance owing to its exceptional ability to deplete sessile lymph node T cells. However, if initiated at the time of transplantation, alpha-CD3-IT alone elicits a proinflammatory cytokine response, precluding establishment of tolerance. METHODS: Four groups of rhesus monkeys received kidney allografts and immunosuppression. Three groups received alpha-CD3-IT alone or alpha-CD3-IT supplemented with 15-deoxyspergualin (DSG) and/or methylprednisolone (MP). One group received alpha-CD3-monoclonal antibody with DSG and MP. Cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: Supplementing peritransplant alpha-CD3-IT treatment with a brief course of DSG and MP promoted rejection-free kidney allograft acceptance in 75% of macaques followed for up to 550 days. Among those given alpha-CD3-IT alone or with MP, none were long-term survivors. Tolerance developed after alpha-CD3-IT, DSG, and MP treatment, but not when the unconjugated a-CD3 monoclonal antibody was substituted for IT. Systemic production of proinflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha induced after peritransplant alpha-CD3-IT was prevented only in animals given DSG. Despite high levels of interleukin (IL)-12 in the first month after transplant, tolerant recipients exhibited IL-12 resistance, as evidenced by baseline plasma levels of IFN-gamma but elevated IL-4. DSG was shown to inhibit IL-12-driven IFN-gamma production by a mechanism associated with inhibition of nuclear factor kappa-B. CONCLUSIONS: In this model, peritransplant induction of tolerance is promoted by efficient elimination of sessile lymph node T cells and control of the proinflammatory IFN-gamma response by a mechanism that appears to involve resistance to IL-12.