MKK4 and metastasis suppression: a marriage of signal transduction and metastasis research

MAP kinase kinase 4 (MKK4) is a member of the stress-activated protein kinase (SAPK) signaling cascade and is involved in the regulation of many cellular processes. We have recently demonstrated a functional role for MKK4 in the suppression of metastases. In this review, we discuss the established cellular and biochemical functions of MKK4, as well as a new function for MKK4 as a metastasis suppressor gene. Because of the importance of signaling studies to this translational work, a detailed example of the strategy and tools that can be employed to define the biochemical mechanism of MKK4-mediated metastasis suppression is presented. Finally, the potential therapeutic utility of these findings is discussed.     

Identification of a new member of the PBAN family of neuropeptides from the fire ant, Solenopsis invicta

Neuropeptide hormones produced by neurosecretory cells in the central or peripheral nervous systems regulate various physiological and behavioral events during insect development and reproduction. PBAN/Pyrokinin is a major neuropeptide family, characterized by a 5‐amino‐acid C‐terminal sequence, FXPRLamide. This family of peptides has been implicated in regulating various physiological functions including, pheromone biosynthesis, muscle contraction, diapause induction or termination, melanization, and puparium formation in different insect species. In the present study, we report a new member of the PBAN family from the red imported fire ant, Solenopsis invicta, Soi‐PBAN, composed of 26‐AA (GSGEDLSYGDAYEVDEDDHPLFVPRL). Three additional peptides were deduced from Soi‐PBAN cDNA: 15‐AA (TSQDIASGMWFGPRL), 8‐AA (QPQFTPRL) and 9‐AA (LPWIPSPRL), that correspond to diapause hormone (DH), β‐neuropeptide (NP), and γ‐NP, which are found in many lepidopteran moths. Five peptides, DH, α, β, γ NPs, and PBAN are encoded from PBAN genes of lepidopteran moths, but in the fire ant the α‐NP is missing. Each of the four synthetic peptides from the fire ant Soi‐PBAN cDNA showed significant pheromonotropic activity in a moth model, indicating that these peptides are cross‐reactive. Soi‐β‐NP induced the highest amount of pheromone production of the four peptides evaluated. The Soi‐DH homologue had the lowest pheromonotropic activity, but was still significantly greater than control values. When the deduced amino acid sequences (entire ORF domains) from Soi‐PBAN cDNA were compared with other known sequences, the fire ant was most similar to the honey bee, but phylogenetically distant from moth and beetle species. Soi‐PBAN (26‐AA) unlike the other three peptides shows a low degree of sequence identity with honeybee PBAN (33‐AA). Based on the amino acid sequences encoded from insect PBAN genes identified to date, neuropeptide diversity is correlated with the taxonomic or phylogenetic classification of Insecta. From the present study we report the first neuropeptide identified and characterized from the central nervous system of Formicidae.     

How to quantify iron in an aqueous or biological matrix: a technical note

Iron oxide (nano)particles are powerful contrast agents for MRI and tags for magnetic cellular labeling. The need for quantitative methods to evaluate the iron content of contrast media solutions and biological matrixes is thus obvious. Several convenient methods aiming at the quantification of iron from iron oxide nanoparticle‐containing samples are presented. Copyright © 2009 John Wiley & Sons, Ltd.     

New radiological typing system for rhinosinusitis and comparison with existing system: Initial finding

The objective of this study was to determine whether the proposed Malan radiological sinusitis typing (RST) system facilitated a level of agreement and ease of use comparable with the Lund–Mackay (LM) system for chronic rhinosinusitis. Ten observers (one otolaryngologist and nine radiologists), in two separate centres (regional and tertiary), blinded to all clinical data, used these two systems to independently and randomly score and type 15 sets of scans, recording the time to score each film. Using unweighted kappa scores, both methods facilitated a moderate level of agreement, slightly better with the LM system. The Malan system is more time efficient. Preliminarily, this study shows that the Malan RST system is easy to apply with a comparable level of agreement. The Malan RST system is a focused attempt at classifying disease extent radiologically and correlating it to a surgical approach. It emphasizes that scoring systems are vulnerable and proves to be superior to the LM system as a surgical planning tool. To score sinus disease, a Quality‐of‐Life questionnaire in association with this typing method is more appropriate.     

Postoperative complications associated with 25-gauge pars plana vitrectomy.

BACKGROUND AND OBJECTIVE: To report postoperative complications in eyes undergoing 25-gauge pars plana vitrectomy (PPV). PATIENTS AND METHODS: Seventy consecutive eyes that underwent 25-gauge PPV for various indications, including epiretinal membrane, non-clearing vitreous hemorrhage, and idiopathic macular hole, and had a minimum follow-up of 12 weeks were reviewed retrospectively. Main outcome measures included best-corrected Snellen visual acuity, intraocular pressure (IOP), intraoperative complications, and postoperative complications. RESULTS: The mean visual acuity improved from 20/368 preoperatively to 20/105 postoperatively (P < .00005). Intraoperative complications included retinal tears in 2 eyes (2.9%). Postoperative complications included cataract progression in 17 eyes (42.5%), cystoid macular edema exacerbation in 5 eyes (7.1%), and retinal detachment in 1 eye (1.4%). Postoperative day 1 IOP was statistically lower than preoperative IOP in fluid-filled eyes (P = .031) but not in eyes filled with intravitreal air (P = .30) or gas (P = .52). Sclerotomy sutures were required intraoperatively in 5 eyes (7.1%) and postoperative day 1 hypotony was noted in 4 eyes (5.7%). All of these complications were noted in fluid-filled eyes except for one case of postoperative day 1 hypotony with gas tamponade. CONCLUSIONS: Intraoperative and postoperative complications were rare in this series of 25-gauge PPV. Postoperative cataract progression and hypotony were the most common complications. Fluid-filled eyes appear to have a higher risk of wound leakage and postoperative hypotony after 25-gauge PPV than eyes with air or gas tamponade.     

Pulmonary and systemic immune response to inhaled multiwalled carbon nanotubes.

Inhalation of multiwalled carbon nanotubes (MWCNTs) at particle concentrations ranging from 0.3 to 5 mg/m3 did not result in significant lung inflammation or tissue damage, but caused systemic immune function alterations. C57BL/6 adult (10- to 12-week) male mice were exposed by whole-body inhalation to control air or 0.3, 1, or 5 mg/m3 respirable aggregates of MWCNTs for 7 or 14 days (6 h/day). Histopathology of lungs from exposed animals showed alveolar macrophages containing black particles; however, there was no inflammation or tissue damage observed. Bronchial alveolar lavage fluid also demonstrated particle-laden macrophages; however, white blood cell counts were not increased compared to controls. MWCNT exposures to 0.3 mg/m3 and higher particle concentrations caused nonmonotonic systemic immunosuppression after 14 days but not after 7 days. Immunosuppression was characterized by reduced T-cell-dependent antibody response to sheep erythrocytes as well as T-cell proliferative ability in presence of mitogen, Concanavalin A. Assessment of nonspecific natural killer (NK) cell activity showed that animals exposed to 1 mg/m(3) had decreased NK cell function. Gene expression analysis of selected cytokines and an indicator of oxidative stress were assessed in lung tissue and spleen. No changes in gene expression were observed in lung; however, interleukin-10 (IL-10) and NAD(P)H oxidoreductase 1 mRNA levels were increased in spleen.     

A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-alpha monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10-50+ weeks). There was no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.     

Differences in resting energy expenditure between black and white smokers: implications for postcessation weight gain

OBJECTIVE: To examine differences in resting energy expenditure (REE) between black and white smokers in order to determine whether REE might contribute to postcessation weight gain. DESIGN: Cross-sectional and prospective investigation of ethnic differences in REE. Differences in REE between black and white smokers were examined at baseline while all participants were smoking, and again during 2 weeks of abstinence from smoking. SETTING: Memphis, Tennessee, USA. SUBJECTS: Sixty-six black and 112 white smokers (age 30.4 y; cigarettes per day 21.4; weight 71.7 kg; body mass index 24.5 kg/m2). RESULTS: Black smokers had a significantly lower baseline REE after adjusting for gender and body weight. Changes in REE following smoking cessation did not differ by ethnicity. CONCLUSIONS: These results suggest that black smokers may be more energy efficient, which could contribute to ethnic differences in postcessation weight gain.     

Acute renal failure in a neonate due to pelviureteric candidal bezoars successfully treated with long-term systemic fluconazole

Systemic candidiasis with renal involvement is a rare but well-recognized complication during intensive care treatment in very-low-birth-weight infants. We report a term neonate who developed anuria associated with bilateral bezoar formation in the renal pelvis and candidemia. The treatment consisted of placement of a nephrostomy tube in the left kidney, short-term irrigation with amphotericin B and iv, and later, oral administration of fluconazole.