Magnetic resonance imaging assessment of substantia nigral iron deposition in Parkinson's disease: a meta-analysis.

OBJECTIVE: The pathogenesis of Parkinson's disease (PD) is associated with abnormal iron accumulation. Magnetic resonance imaging (MRI) studies have shown that patients with Parkinson's disease have an increased amount of iron in their substantia nigra (SN). We have undertaken a meta-analysis of studies using MRI in PD, to explore the potential role of MRI in diagnosing PD using abnormal iron deposition in SN as a candidate biomarker. MATERIALS AND METHODS: Searches of PubMed, Embase, and Medline databases revealed 16 studies that compared PD patients and healthy controls (HC). A sensitivity analysis and subgroup analysis were performed to evaluate the reliability of our results. Estimates were pooled by the fixed-effects model. As an expression of I2, we computed the proportion of variation due to heterogeneity. RESULTS: We included 16 studies with sample sizes of 435 PD and 355 HC in our meta-analysis. Results showed that SN iron deposition was significantly elevated (p<0.00001) in patients with PD compared to HC ones (SMD=0.72, 95% confidence interval 0.57 to 0.87, p<0.00001). CONCLUSIONS: Our findings, based on a homogeneous group-level analysis, suggest that MRI-based SN iron deposition could be used to distinguish PD from HC. For a more rigorous investigation of SN iron deposition in PD, larger cohort studies are needed.

MRI findings for diagnosis of postoperative foreign body granulomas versus recurrent tumours in patients of brain tumour surgery.

AIM: To evaluate the postoperative magnetic resonance imaging (MRI) findings of intracranial foreign body granulomas (FBGs) and true recurrent tumours (RTs) and thus lead to a basis for management decision-making. MATERIALS AND METHODS: Twenty-two patients with previous brain tumour surgery were diagnosed clinically with RT and underwent surgery. Re-operative pathology revealed FBG in eight patients and RT in 14 patients. MRI findings before the initial operation were compared to those before the re-operation. RESULTS: Features of FBGs versus RTs on MRI were as follows: (1) mean lesion size: 1.3 ± 0.7 (0.5-2.6) versus 3.2 ± 1.7 (1.1-6.3) cm (p=0.001, odds ratio [OR] = 4.18); (2) hypointensity on T2-weighted imaging (WI): 6/8 (75%) versus 0/14 (0%; p<0.001, OR=75.4); (3) non-restricted diffusion on diffusion-WI (DWI): 6/8 (75%) versus 2/14 (14.3%; p=0.008, OR=18); and (4) "ring and bubble" appearance on contrast-enhanced T1WI: 7/8 (87.5%) versus 2/14 (14.3%; p=0.001, OR=42). In comparison with their original tumours, the FBGs in the FBG group showed significantly lower T2 signal intensity, lower signal on DWI, and more cases of non-restricted diffusion on DWI (p=0.04, 0.04, 0.04, respectively). CONCLUSION: On brain MRI, FBGs can be differentiated from RTs by their relatively smaller size, hypointensity on T2WI, lack of restricted diffusion on DWI, and "ring and bubble" appearance on contrast-enhanced T1WI. Comparing the MRI findings of the focal lesion in the tumour bed with those of the original tumour is suggested to enhance diagnostic confidence.

Correction to: CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.

Following publication of their article "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation", the authors reported an error in Fig.6b. α-Tubulin image of rCCN2 treatment  (upper panel in CL1-5) only showed eight lanes, when there should be nine.

Prescription trends and the selection of initial oral antidiabetic agents for patients with newly diagnosed type 2 diabetes: a nationwide study.

OBJECTIVES: The aim of this study was to examine the characteristics of patients, physicians, and medical facilities, and their association with prescriptions that do not include metformin as the initial oral antidiabetic agent. STUDY DESIGN: Observational, cross-sectional study. METHODS: Patients with incident type 2 diabetes between January 1, 2006, and December 31, 2010, were identified from the Taiwan National Insurance Research Database. We describe trends in the initial prescription of antidiabetic medications that do not contain metformin during the study period. A multivariable logistic model and a multilevel linear model were used in the analysis of factors at a range of levels (patient, physician, and medical facility), which may be associated with the selection of oral antidiabetic drugs. RESULTS: During the study period, the proportion of prescriptions that did not include metformin declined from 43.8% to 26.2%. Male patients were more likely to obtain non-metformin prescriptions (adjusted odds ratio [OR]: 1.15; 95% confidence interval [CI]: 1.08-1.23), and the likelihood that a patient would be prescribed a non-metformin prescription increased with age. Physicians aged ≥35 years and those with specialties other than endocrinology tended to prescribe non-metformin prescriptions. Metformin was less commonly prescribed in for-profit hospitals (adjusted OR: 1.34, 95% CI: 1.11-1.61) and hospitals in smaller cities (adjusted OR: 1.28, 95% CI: 1.05-1.57) and rural areas (adjusted OR: 1.83, 95% CI: 1.32-2.54). CONCLUSIONS: Disparities continue to exist in clinical practice with regard to the treatment of diabetes. These inequalities appear to be linked to a variety of factors related to patients, physicians, and medical facilities. Further study will be required to understand the effects of continuing medical education in enhancing adherence to clinical guidelines.

B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway.

This corrects the article DOI: 10.1038/onc.2014.43.

The diagnostic utility of preoperative breast magnetic resonance imaging (MRI) and/or intraoperative sub-nipple biopsy in nipple-sparing mastectomy.

BACKGROUND: The necessity of routine sub-nipple biopsy was uncertain, and the role of preoperative magnetic resonance imaging (MRI) in detecting nipple invasion in patients who have been selected for nipple sparing mastectomy (NSM) has not been adequately evaluated. METHODS: We retrospectively collected and analyzed the medical and surgical records of 434 patients with primary operable breast cancer who met the criteria for NSM and underwent breast surgery during the period January 2011 to December 2015. Patients were stratified into three risk groups (low, intermediate, and high) according to tumor size and tumor-to-nipple distance. RESULTS: Among the 434 patients in this study, 29 (6.7%) had occult invasion of the nipple-areola complex (NAC). Sub-nipple biopsy had a sensitivity of 84.6%, a specificity of 100%, a false negative rate of 1.2%, a false positive rate of 0%, and an overall accuracy rate of 98.8% in confirming NAC invasion. The NAC invasion rate was 0% in the low-risk group, 5.1% in the intermediate-risk group, and 19.7% in the high-risk group (P < 0.01). The overall NPV of preoperative MRI for predicting NAC invasion was 94.8%. Cost analysis revealed that the cost of NSM with sub-nipple biopsy was significantly higher than that of NSM alone, with a mean difference in cost of USD 238.5 (P < 0.01). CONCLUSION: The high negative predictive value of MRI for NAC invasion is useful for selection of patients receiving NSM. Sub-nipple biopsy is a reliable procedure to detect occult NAC invasion, however, routine use is not cost-effect for low risk patients.

Sensititre® MYCOTB MIC plate for drug susceptibility testing of Mycobacterium tuberculosis complex isolates.

SETTING: National Tuberculosis Clinical Laboratory, China. OBJECTIVE: To evaluate the accuracy and feasibility of the MYCOTB MIC plate in anti-tuberculosis drug susceptibility testing. DESIGN: MYCOTB testing of Mycobacterium tuberculosis isolates, the Löwenstein-Jensen (LJ) proportion method and the resurazine microtitre assay (REMA), which is extensively used for in-house assay for minimal inhibition concentration (MIC) testing, were performed simultaneously for comparison. A total of 126 clinical isolates were tested using both MYCOTB and the LJ proportion method against 12 anti-tuberculosis drugs; 80 were also tested using REMA. RESULTS: Categorical agreement between MYCOTB and the LJ proportion method was 99.2% for rifampicin, ofloxacin, amikacin, kanamycin and cycloserine, and 98.4% for isoniazid and para-aminosalicylic acid; ethambutol (EMB) had the lowest agreement (86.5%). The overall categorical agreement between MYCOTB and REMA ranged between 98.8% and 100%. MYCOTB outcomes, interpreted on day 10 and 21, were stable for all drugs except EMB. CONCLUSION: MYCOTB is a rapid, convenient, quantitative and accurate method for testing both first- and second-line anti-tuberculosis drugs.

Opposing effects of Sca-1(+) cell-based systemic FGF2 gene transfer strategy on lumbar versus caudal vertebrae in the mouse.

Our previous work showed that a Sca-1(+) cell-based FGF2 therapy was capable of promoting robust increases in trabecular bone formation and connectivity on the endosteum of long bones. Past work reported that administration of FGF2 protein promoted bone formation in red marrow but not in yellow marrow. The issue as to whether the Sca-1(+) cell-based FGF2 therapy is effective in yellow marrow is highly relevant to its clinical potential for osteoporosis, as most red marrows in a person of an advanced age are converted to yellow marrows. Accordingly, this study sought to compare the osteogenic effects of this stem cell-based FGF2 therapy on red marrow-filled lumbar vertebrae with those on yellow marrow-filled caudal vertebrae of young adult W(41)/W(41) mice. The Sca-1(+) cell-based FGF2 therapy drastically increased trabecular bone formation in lumbar vertebrae, but the therapy not only did not promote bone formation but instead caused substantial loss of trabecular bone in caudal vertebrae. The lack of an osteogenic response was not due to insufficient engraftment of FGF2-expressing Sca-1(+) cells or inadequate FGF2 expression in caudal vertebrae. Previous studies have demonstrated that recipient mice of this stem cell-based FGF2 therapy developed secondary hyperparathyroidism and increased bone resorption. Thus, the loss of bone mass in caudal vertebrae might in part be due to an increase in resorption without a corresponding increase in bone formation. In conclusion, the Sca-1(+) cell-based FGF2 therapy is osteogenic in red marrow but not in yellow marrow.

Cardiovascular risks associated with second-line oral antidiabetic agents added to metformin in patients with Type 2 diabetes: a nationwide cohort study.

AIM: To compare the cardiovascular risks associated with second-line oral antidiabetic agents added to initial metformin therapy in a large nationwide observational study. METHODS: We conducted a nationwide retrospective cohort study using the Taiwan National Health Insurance database. A total of 36 118 users of different add-on oral antidiabetic agents (sulphonylureas, glinides, pioglitazone, α-glucosidase inhibitors and dipeptidyl peptidase-4 inhibitors) after initial metformin therapy were included in the analysis. The reference group was sulphonylureas added to metformin, the most commonly used combination regimen. The main outcomes of interest were hospitalizations for any cardiovascular event including acute myocardial infarction, congestive heart failure and ischaemic stroke. In the main analysis, all patients were followed within their initiation groups until the study end, disregarding any changes in treatment status over time. RESULTS: In intention-to-treat analyses, there was no difference in the risk of any cardiovascular event among the add-on combination treatment groups, but significantly lower risks of acute myocardial infarction were found for the glinides plus metformin treatment group (crude hazard ratio 0.52, adjusted hazard ratio 0.39; 95% CI 0.20-0.75) and for the α-glucosidase inhibitors plus metformin treatment group (crude hazard ratio 0.63, adjusted hazard ratio 0.54; 95% CI 0.31-0.95). No difference in risk of congestive heart failure or ischaemic stroke risk was found among the combination treatment groups. In secondary as-treated analyses, similar but less significant associations were found as compared with the primary intention-to-treat analyses for all treatment groups. CONCLUSION: There were no differences in overall cardiovascular risks among several add-on second-line oral antidiabetic agents; however, glinide plus metformin and α-glucosidase inhibitors plus metformin combination therapies might be associated with lower risks of acute myocardial infarction.

B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway.

B-cell lymphoma/leukemia 10 (BCL10) is an apoptotic regulatory protein related to advanced TNM stage and disease recurrence in oral squamous cell carcinoma (OSCC). However, the regulatory mechanism of BCL10 in OSCC progression is still unknown. Here, we showed that knockdown of endogenous BCL10 could significantly reduce cell migration and invasion abilities, retard cell proliferation by G0/G1 phase accumulation and inhibit tumorigenicity in vivo. In molecular level, we identified S100P as a crucial downstream effector of BCL10-inhibited OSCC progression by high-throughput microarray analysis. S100P messenger RNA and protein expression levels were significantly diminished in silenced-BCL10 clones, and transfected S100P expression plasmids restored migration, invasion, proliferation abilities and tumorigenicity in shBCL10 transfectants. Furthermore, we provided evidence that BCL10 regulated S100P expression through signal transducers and activators of transcription 1 (STAT1) and activating transcription factor 4 (ATF4). Knockdown of BCL10 decreased S100P promoter activity, but showed no effect in truncated STAT1/ATF4 S100P promoter.  In addition, we also found that the P50/P65 signaling pathway was involved in BCL10-enhanced OSCC progression. Restored S100P in silenced-BCL10 clones could markedly reverse P65 activation via outside-in signaling. Taken together, we discovered a novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and will be beneficial for developing therapeutic strategy against advanced OSCC.

Participation of c-FLIP in NLRP3 and AIM2 inflammasome activation.

Cellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of caspase-8 and is required for macrophage survival. Recent studies have revealed a selective role of caspase-8 in noncanonical IL-1ß production that is independent of caspase-1 or inflammasome. Here we demonstrated that c-FLIP(L) is an unexpected contributor to canonical inflammasome activation for the generation of caspase-1 and active IL-1ß. Hemizygotic deletion of c-FLIP impaired ATP- and monosodium uric acid (MSU)-induced IL-1ß production in macrophages primed through Toll-like receptors (TLRs). Decreased IL-1ß expression was attributed to a reduced activation of caspase-1 in c-FLIP hemizygotic cells. In contrast, the production of TNF-α was not affected by downregulation in c-FLIP. c-FLIP(L) interacted with NLRP3 or procaspase-1. c-FLIP is required for the full NLRP3 inflammasome assembly and NLRP3 mitochondrial localization, and c-FLIP is associated with NLRP3 inflammasome. c-FLIP downregulation also reduced AIM2 inflammasome activation. In contrast, c-FLIP inhibited SMAC mimetic-, FasL-, or Dectin-1-induced IL-1ß generation that is caspase-8-mediated. Our results demonstrate a prominent role of c-FLIP(L) in the optimal activation of the NLRP3 and AIM2 inflammasomes, and suggest that c-FLIP could be a valid target for treatment of inflammatory diseases caused by over-activation of inflammasomes.

CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.

CCN family protein 2 (CCN2), also known as connective tissue growth factor, is a secreting protein that modulates multiple cellular events. We previously demonstrated the metastasis-suppressive effect of CCN2 in lung cancer cells. In this study, we investigate the role of CCN2 in anoikis, a form of programmed cell death that is critical in suppressing cancer metastasis. CCN2 binds to the epidermal growth factor receptor (EGFR) and triggers ubiquitination by inhibiting the formation of the ß-pix/Cbl complex, resulting in the degradation of EGFR. Binding of CCN2 to EGFR suppresses the phosphorylation of c-Src and extracellular signal-regulated kinase but increases the expression of death-associated protein kinase, which leads to anoikis. Overall, our findings provide evidence validating the use of CCN2 as an anti-metastatic therapy in lung cancer patients, and prospect a potential therapeutic synergy between CCN2 and the anti-EGFR antibody for the treatment of lung cancer.

Connective tissue growth factor modulates oral squamous cell carcinoma invasion by activating a miR-504/FOXP1 signalling.

Connective tissue growth factor (CTGF) is a multi-functional secreted protein, and it has been shown either to promote or suppress tumor progression among different kinds of cancers. Here, we investigated the role of CTGF in oral squamous cell carcinoma (OSCC) invasion and metastasis. In five OSCC cell lines, endogenous CTGF negatively correlated with invasiveness. Exogenous CTGF protein or forced expression of CTGF gene in the oral cancer cell line SAS significantly decreased their invasive and migratory abilities. MicroRNA (miRNA) microarray analysis was performed in CTGF-overexpressed SAS cells (SAS/CTGF-M3) versus control cells to investigate the mechanism of CTGF-mediated inhibition of OSCC invasion. Among the miRNAs regulated by CTGF, miR-504 and miR-346 were the top two miRNAs downregulated in CTGF transfectants, and the result was confirmed by quantitative reverse transcriptase-PCR. Ectopic miR-504 increased migration and invasion in SAS/CTGF-M3, however, miR-346 did not have such impact on migration/invasion. Furthermore, we identified FOXP1, a member of forkhead transcription factors, as a target gene that takes part in the miR-504-induced cellular invasion. Knockdown of FOXP1 increased invasiveness in SAS/CTGF-M3, confirming the signal axis of CTGF/miR-504/FOXP1 in OSCC. Animal experiments showed that SAS/CTGF-M3-formed orthotopic tumors were associated with a lesser invasive phenotype than control cells. Expression of miR-504 in SAS/CTGF-M3 increased lymph node metastasis, and co-expression of FOXP1 in miR-504-transfected SAS/CTGF-M3 alleviated miR-504-induced metastasis. In OSCC samples, high CTGF was associated with a lower clinical stage and a better outcome. A reverse correlation between CTGF and miR-504, miR-504 and FOXP1, and a positive correlation between CTGF and FOXP1 were shown. Our study discovers a novel signal pathway involving the regulation of miRNA machinery by a secreted cytokine, which will be beneficial for developing therapeutic strategy against advanced OSCC.

Are there ethnic differences in impulsive/compulsive behaviors in Parkinson's disease?

BACKGROUND AND PURPOSE: Recent studies have suggested increased prevalence of impulsive/compulsive behaviors (ICB) in patients with Parkinson's disease (PD) as compared to general population in different ethnic groups. The spectrum of these behaviors includes dopamine dysregulation syndrome (DDS), punding, pathological gambling (PG), hypersexuality (HS), binge eating (BE), and compulsive shopping (CS). METHODS: Two hundred and seventy-eight consecutive patients with idiopathic PD regularly followed-up at an outpatient clinic were interviewed and screened for the ICB between September 2008 and December 2008 using designated diagnostic criteria. All patients who screened positive for ICB or obsessive-compulsive disorder (OCD) were further confirmed by an experienced psychiatrist. RESULTS: Of all the studied patients, 15 patients confirmed to have ICB (lifetime prevalence: 5.60%), 3 (1.12%) were diagnosed to have DDS, 1 (0.37%) punding, 4 (1.49%) PG, 8 (2.99%) HS, 1 (0.37%) BE, 0 (0%) CS. OCD was found in one patient (0.37%). CONCLUSIONS: The prevalence of ICB is lower in Taiwan as compared with the Caucasians, with similar risk factors. The possible reasons include differences in ethnicity, environmental, cultural, and social factors as well as the dosage and selection of dopaminergic medications.

Nutrition Knowledge, Attitude and Practice of Teachers in Rehabilitation Centres in Northern Malaysia

Introduction: Persons with disabilities (PWD) are susceptible to malnutrition. Caregivers or teachers in rehabilitation centres may not be adequately trained in nutrition management of PWD. The aims of this study were (i) to assess the nutrition knowledge, attitude and practice among teachers in community-based rehabilitation centres for PWD; and (ii) to evaluate changes in the nutrition knowledge and attitude of the teachers before and after exposure to a training workshop on nutrition management for PWD. Methods: A cross-sectional survey was conducted using a guided self-administered Nutrition Knowledge, Attitude and Practice Questionnaire on Persons with Disabilities (KAP-nOKU), among a convenience sample of 210 teachers. Forty-five of them further participated in a nutrition training workshop and completed the post-test evaluation on knowledge and attitude of the same measures. Results: At baseline, the teachers’ average knowledge, attitude and practice scores were 13.80±3.73 for knowledge (below 50th percentile); 51.49±4.08 for attitude (above 75th percentile); and 48.08±3.61 for practice (between 50th and 75th percentile). There was significant positive correlations between knowledge and attitude (r=0.343, p<0.05), as well as between attitude and practice (r=0.147, p<0.05). After exposure to a 3-day nutrition workshop, significant improvements in the teachers’ knowledge and attitude were observed, whereby teachers’ knowledge score increased from 14.20±3.80 to 25.38±2.36 and from 51.16±3.97 to 55.20±4.41 for attitude (p<0.001). Conclusion: Nutrition intervention was associated with improvement in short term knowledge and attitude of the teachers. Sustainable interventional strategies are needed to enhance the nutrition knowledge and skills of teachers of PWD.

Comparison of array comparative genomic hybridization (aCGH) to FISH and cytogenetics in prognostic evaluation of chronic lymphocytic leukemia.

INTRODUCTION: High-resolution array comparative genomic hybridization (aCGH) is a method of evaluating chromosomal alterations over the entire genome. We compared aCGH with routine cytogenetics and FISH in detecting genetic alterations in chronic lymphocytic leukemia (CLL). METHODS: Array comparative genomic hybridization testing was performed on 55 cases of CLL in addition to a standard panel of FISH probes (ATM on 11q22, trisomy 12, 13q14, p53 on 17p13). The frequency of detecting abnormalities was compared, and discordant results between methodologies were compared. RESULTS: Fifty-five CLL cases [male to female ratio of 2.2:1 and a mean age of 71 (52-90)] were analyzed by both aCGH and FISH. This group of CLL cases showed genetic abnormalities by FISH (60%; 27/45). In contrast to FISH, aCGH detected genetic abnormalities in 82% (45/55) of CLL cases; aCGH identified genetic abnormalities not detected by FISH studies in 16% (7/45) of cases, whereas FISH identified abnormalities not detected by aCGH in only 7% (3/45) of cases. Rare recurring genetic alterations were detected by aCGH including losses in 6q, 8p, 10q, 14q32, and 18q and gains in 10q. DISCUSSION: Our findings suggest aCGH is an effective technique for evaluating recurring genetic abnormalities in CLL and improves on standard FISH in detecting genetic abnormalities in CLL.

Temporal features of magnetic resonance imaging and spectroscopy in non-ketotic hyperglycemic chorea-ballism patients.

BACKGROUND: Non-ketotic hyperglycemic chorea-ballism (NKHCB) had special reversible hyperintense on T1-weighted imaging (T1WI) lesion in comparsion to gray matter. However, the mechanism accounts for these lesions is still unclear. METHODS: Patients diagnosed with NKHCB were recruited from 2002 to 2004. The demographic, clinical, magnetic resonance imaging (MRI), and spectroscopy (MRS) features were recorded at acute and remission phase. RESULTS: In 18 patients with NKHCB, the blood sugar level at onset was significantly higher than that after being free from chorea-ballism (419.50 +/- 257.33 vs. 198.22 +/- 53.97 mg/dl, P = 0.001). The serum osmolality dropped from 318.33 +/- 15.21 mOsm/kg at onset to 292.50 +/- 7.85 mOsm/kg after recovery (P < 0.001). All patients displayed T1 hyperintense lesions at contralateral basal ganglia at acute phase. Eight patients receiving follow-up MRI at remission phase, all T1 hyperintense lesions at the basal ganglia regressed. The ratios between choline-containing compounds and creatine at acute and remission phases were significant higher in lesion than in normal side, respectively (acute phase: 1.12 +/- 0.23 vs. 0.72 +/- 0.28, P = 0.038; remission phase: 1.23 +/- 0.47 vs. 0.68 +/- 0.15, P = 0.013). The lactate peaks present at 1.3 ppm on the lesion side either in acute or in remission phase of most case. CONCLUSIONS: The clinical, MRI, and MRS findings suggest that the mechanisms responsible for NKHCB may be a reversible ischaemia insult potentiated by hyperglycemia.

Interleukin-1 receptor antagonist enhances islet engraftment without impacting serum levels of nitrite or osteopontin.

Interleukin-1beta (IL-1beta)-mediated early islet graft dysfunction and loss of islet mass can occur in different phylogenic types of islet transplantation. Large quantities of interleukin-1 receptor antagonist (IL-1RA) have been demonstrated to impede IL-1beta-mediated adverse effects on islet grafts in allo- and xenotransplantation. To clarify the influence of IL-1RA on early function and mass change, as well as long-term hypoglycemic effects of islet isografts, we studied streptozotocin-induced diabetic C57BL/6 mice infected with replication-defective adenovirus carrying the mouse IL-1RA cDNA gene. This vector increased the mean serum level of IL-1RA to 8 ng/mL, approximately three times greater than for mice receiving adenovirus carrying the beta-galactosidase (beta-Gal) gene. The blood glucose levels declined faster and the insulin content of the graft was significantly higher on day 10 following transplantation among mice receiving mIL-1RA gene than the controls. Nevertheless, the insulin content of the pancreatic remnant did not differ among mice in the IL-1RA, beta-Gal, and vehicle control groups. Serum levels of nitrite and osteopontin before and 3 days after islet transplantation did not differ considerably among the IL-1RA, beta-Gal, and vehicle groups. Compared with the beta-Gal group, temporary posttransplantation hyperglycemia was significantly shortened in the IL-1RA group mice. Removal of graft-bearing kidneys at 13 weeks following transplantation caused recurrence of hyperglycemia in all treated diabetic mice. The insulin content of pancreatic remnants removed at 15 weeks following transplantation was similar in the IL-1RA and beta-Gal groups. In conclusion, a mildly elevated serum concentration of IL-1RA protected and enhanced engraftment of islet isografts immediately after transplantation.