Spiegelmer Inhibition of MCP-1/CCR2--Potential as an Adjunct Immunosuppressive Therapy in Transplantation.

The rejection process remains the key unsolved issue after transplantation of disparate tissue. The CC chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) has been reported to be involved in the process of alloimmune interaction. Spiegelmers are l-oligonucleotides that can be designed to bind to pharmacologically relevant target molecules. Here, we tested a high-affinity Spiegelmer-based MCP-1 inhibitor (mNOX-E36) in an allogeneic heart transplant model. Fully vascularized allogeneic heterotopic heart transplantations from BALB/c to C57BL/6 mice were performed. Mice were either treated with the anti-MCP-1-Spiegelmer (mNOX-E36) in monotherapy or in combination with subtherapeutic doses of cyclosporine A (CsA) (10 mg/kgBW/day) for 10 days. Controls received equivalent doses of a non-functional Spiegelmer (revmNOX-E36). Graft survival of allogeneic heart transplants was slightly but significantly prolonged under mNOX-E36 monotherapy (median graft survival 10 day ± 0.7) compared to revmNOX-E36 (median graft survival 7 day ± 0.3; P = 0.001). A synergistic beneficial effect could be seen when mNOX-E36 was administered in combination with subtherapeutic doses of CsA (18 day ± 2.8 versus 7 day ± 0.3; P < 0.0001). Levels of inflammatory cytokines and 'alarmins' were significantly reduced, and the number of F4/80(+) cells was lower under combination therapy (1.8% ± 1.3%; versus 14.6% ± 4.4%; P = 0.0002). This novel inhibitor of the MCP-1/CCR2 axis (mNOX-E36), which has already proven efficacy and tolerability in early clinical trials, alleviates acute rejection processes in allogeneic transplantation especially when combined with subtherapeutic doses of CsA. Thus, mNOX-E36 may have potential as an adjunct immunomodulatory agent.

Screening for self-plagiarism in a subspecialty-versus-general imaging journal using iThenticate.

BACKGROUND AND PURPOSE: Self-plagiarism is a form of research misconduct that can dilute the credibility and reputation of a scientific journal, as well as the represented specialty. Journal editors are aware of this problem when reviewing submissions and use on-line plagiarism-analysis programs to facilitate detection. The American Journal of Neuroradiology (AJNR) uses iThenticate to screen several submitted original research manuscripts selected for review per issue and retrospectively assesses 3 issues per year. The prevalence of self-plagiarism in AJNR was compared with that in Radiology; the necessity and cost of more extensive screening in AJNR were evaluated. MATERIALS AND METHODS: The self-duplication rate in AJNR original research articles was compared with that in Radiology, a general imaging journal that screens all submitted original research manuscripts selected for review by using iThenticate. The rate of self-duplication in original research articles from 2 randomly selected 2012 AJNR issues was compared with the rate in the prior year to gauge the need for more extensive screening. A cost analysis of screening all submitted original research manuscripts selected for review by using iThenticate was performed. RESULTS: Using an empiric 15% single-source duplication threshold, we found that the rate of significant self-plagiarism in original research articles was low for both journals. While AJNR had more articles exceeding this threshold, most instances were insignificant. Analyzing 2 randomly chosen issues of AJNR for single-source duplication of >15% in original research articles yielded no significant differences compared with an entire year. The approximate annual cost of screening all submitted original research manuscripts selected for review was US $6800.00. CONCLUSIONS: While the rate of self-plagiarism was low in AJNR and similar to that in Radiology, its potential cost in negative impact on AJNR and the subspecialty of neuroradiology justifies the costs of broader screening.

Spinal epidural lubricant grease collection mimicking traumatic spinal epidural hematoma.

We report an unusual case of a patient with an epidural fluid collection with signal characteristics mimicking an epidural hematoma. The patient presented with myelopathy caused by thoracic spinal cord compression after a traumatic injury to the chest and back. The injury was caused by high-pressure injection of industrial-grade lubricant grease. This case demonstrates that cord compression can be caused by exogenous material in the setting of trauma that can mimic an acute epidural hematoma.

Extended antiretroviral treatment interruption in HIV-infected patients with long-term suppression of plasma HIV RNA.

OBJECTIVES: Evaluation of extended treatment interruption (TI) in chronic HIV infection among patients successfully treated with antiretroviral therapy. METHODS: An observational analysis of 25 patients in a prospectively followed cohort with chronic HIV infection, viral loads <500 HIV-1 RNA copies/mL for at least 6 months, and an interruption in therapy of >/=28 days duration was carried out. Follow up was divided into 3-month time periods for analysis. The effects of time period, stratification group and stratification group by time period interactions on CD4 counts were tested using a mixed model. Univariate comparisons among patient characteristics and responses were performed using Fisher's exact test or the Wilcoxon rank sum test. RESULTS: At initiation of TI, the median CD4 count was 799 cells/microL. TI duration was a median of 7.1 months. HIV RNA rebounded to a median maximum level of 75 000 copies/mL. Maximum viral rebound was significantly greater in patients who were male, had lipodystrophy and had zenith HIV RNA prior to TI of >/=50 000 copies/mL. Lower CD4 cell counts were observed during TI in patients with lipodystrophy, zenith HIV RNA >/=50 000 copies/mL, history of AIDS, HIV infection >/=5 years and presuppression CD4 count

Sequence of the lacZ gene of Escherichia coli.

The nucleotide sequence of the lacZ gene coding for beta-galactosidase (EC 3.2.1.23) in Escherichia coli has been determined. Beta-Galactosidase is predicted to consist of 1023 residues, resulting in a protein with a mol. wt. of 116 353 per subunit. The protein sequence originally determined by Fowler and Zabin was shown to be essentially correct and in an Appendix these authors comment on the discrepancies.

Effects of age and of fasting on the responsiveness of the insulin-secreting mechanism of the islets of Langerhans to glucose.

Insulin responsiveness to glucose of isolated islets of Langerhans was studied in 'younger' and 'older' rats after feeding and fasting for various lengths of time. In 'younger' rats, after prolonged fasting (168 h) the threshold for glucose-stimulated insulin secretion was increased. This was not evident in islets from 'younger' rats fasted for 48 or 89 h. Reductions in increments of insulin secretion with increments in glucose, in the maximum insulin secreted and in the total extractable insulin of the islets were apparent after fasting for 48, 89 and 168 h as compared with islets from fed rats. In 'older' rats, prolonged fasting caused an increase in the threshold for glucose-stimulated insulin secretion, reduced incremental insulin secretion, reduced maximum insulin secretion and reduced total extractable insulin. However, the responses of islets from fed 'older' rats were similar to those of fasted (168 h) 'younger' rats. The threshold levels were similar, and there were no significant differences between increments in insulin secretion, maximum insulin secretion and insulin content of the islets. These experiments show that the responsiveness of islets of Langerhans in rats can be altered by age and fasting.

Effects of arterial or portal ischemia on survival and metabolism of partially and totally depancreatized dogs.

The role of arterial blood flow in hepatic metabolic functions was compared to that of portal flow in two groups of totally depancreatized dogs. Survival times and glucose and nitrogen excretion were significantly greater in dogs with ligation of the hepatic artery than in dogs with an Eck fistula. The dogs with ligated hepatic arteries also showed a significantly slower rise in plasma ketones. The course of diabetes was compared in three additional groups of partially depancreatized dogs consisting of a) dogs with ligated hepatic arteries, b) dogs with Eck fistulas, and c) controls. Hepatic arterial ischemia: 1) increased survival, without insulin treatment (a--650, b--167, c--124 days) 2) did not decrease tracer-determined rate of glucose production 3) led to a greater urinary excretion of glucose, ketone bodies and nitrogen than portal ischemia. Partially depancreatized dogs with either arterial or portal hepatic ischemia maintained a high rate of glucose disappearance on acute deprivation of endogenous insulin (clamping of vessels of their pancreatic remnant) due probably to decreased insulin degradation by the ischemic liver. The dogs died in coma after losing all fat depots. There was severe fatty change in the livers of dogs with hepatic artery ligation, slight in those with Eck fistulas and no fat in the livers of controls.