The dual role of CXCL8 in human CNS stem cell function: multipotent neural stem cell death and oligodendrocyte progenitor cell chemotaxis.

Research into multiple sclerosis (MS) has shown that cells purportedly important to myelin repair within the CNS, namely neural stem cells (NSC) and oligodendrocyte progenitor cells (OPC), are recruited to active lesion sites during the course of the disease. However, over time these cells appear to become depleted or functionally blocked in and around lesions, accompanied by a failure of repair mechanisms. We have previously demonstrated elevated CXCL8 in patients with MS, and hypothesized that this chemokine may play a role in the pathology of this disease.

Monoclonal antibodies for the treatment of cancer.

Over the past decade, the clinical utility of monoclonal antibodies has been realized and antibodies are now a mainstay for the treatment of cancer. Antibodies have the unique capacity to target and kill tumor cells while simultaneously activating immune effectors to kill tumor cells through the complement cascade or antibody-dependent cellular cytotoxicity (ADCC). This multifaceted mechanism of action combined with target specificity underlies the capacity of antibodies to elicit anti-tumor responses while minimizing the frequency and magnitude of adverse events.

Oral acyclovir suppression and neurodevelopment after neonatal herpes.

Background: Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease.

Methods: We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other.

G-DOC: a systems medicine platform for personalized oncology.

Currently, cancer therapy remains limited by a "one-size-fits-all" approach, whereby treatment decisions are based mainly on the clinical stage of disease, yet fail to reference the individual's underlying biology and its role driving malignancy. Identifying better personalized therapies for cancer treatment is hindered by the lack of high-quality "omics" data of sufficient size to produce meaningful results and the ability to integrate biomedical data from disparate technologies. Resolving these issues will help translation of therapies from research to clinic by helping clinicians develop patient-specific treatments based on the unique signatures of patient's tumor.

Unilateral mydriasis due to scopolamine patch.

Case: We report the case of a patient who presented with unilateral mydriasis after a scopolamine patch application. The specific clinical context (cancer) reported here may have led to the misinterpretation of the etiology of mydriasis.

Conclusion: Our case description warns against diagnostic mistakes related to this side effect and highlights the advantages of pilocarpine test in the differential diagnosis of unilateral mydriasis.

Reading baby books: medicine, marketing, money and the lives of American infants.

This article examines American baby books from the late nineteenth through the twentieth century. Baby books are ephemeral publications—formatted with one or more printed pages for recording developmental, health, and social information about infants and often including personal observations, artifacts such as photographs or palm prints, medical and other prescriptive advice, and advertisements. For historians they serve as records of the changing social and cultural worlds of infancy, offering insights into the interplay of childrearing practices and larger social movements.

Effective antibody therapy induces host-protective antitumor immunity that is augmented by TLR4 agonist treatment.

Toll-like receptors are potent activators of the innate immune system and generate signals leading to the initiation of the adaptive immune response that can be utilized for therapeutic purposes. We tested the hypothesis that combined treatment with a Toll-like receptor agonist and an antitumor monoclonal antibody is effective and induces host-protective antitumor immunity. C57BL/6 human mutated HER2 (hmHER2) transgenic mice that constitutively express kinase-deficient human HER2 under control of the CMV promoter were established.

Efficacy of chronic antidepressant treatments in a new model of extreme anxiety in rats.

Animal models of anxious disorders found in humans, such as panic disorder and posttraumatic stress disorder, usually include spontaneous and conditioned fear that triggers escape and avoidance behaviors. The development of a panic disorder model with a learned component should increase knowledge of mechanisms involved in anxiety disorders. In our ethological model of extreme anxiety in the rat, forced apnea was combined with cold water vaporization in an inescapable situation.

Dual inhibition of SRC and Aurora kinases induces postmitotic attachment defects and cell death.

Increased activity of SRC family kinases promotes tumor invasion and metastasis, and overexpression of the mitotic regulator Aurora kinase A (AURKA) drives tumor aneuploidy and chromosomal instability. These functions nominate SRC and AURKA as valuable therapeutic targets for cancer, and inhibitors for SRC and Aurora kinases are now being used in the clinic. In this study, we demonstrate potent synergy between multiple inhibitors of Aurora and SRC kinases in ovarian and colorectal cancer cell lines, but not in normal ovarian epithelial cell lines.

Increase developmental plasticity of human keratinocytes with gene suppression.

Recent evidence indicates that p53 suppression increased the efficiency of induced pluripotent stem cell (iPSC) generation. This occurred even with the enforced expression of as few as two canonical transcription factors, Oct4 and Sox2. In this study, primary human keratinocytes were successfully induced into a stage of plasticity by transient inactivation of p53, without enforced expression of any of the transcription factors previously used in iPSC generation.

Dynamic modelling of oestrogen signalling and cell fate in breast cancer cells.

Cancers of the breast and other tissues arise from aberrant decision-making by cells regarding their survival or death, proliferation or quiescence, damage repair or bypass. These decisions are made by molecular signalling networks that process information from outside and from within the breast cancer cell and initiate responses that determine the cell's survival and reproduction. Because the molecular logic of these circuits is difficult to comprehend by intuitive reasoning alone, we present some preliminary mathematical models of the basic decision circuits in breast cancer cells that may aid our understanding of their susceptibility or resistance to endocrine therapy.

SPECT/CT in the management of osteochondral lesions of the talus.

Background: The treatment of osteochondral lesion of the talus (OLT) is mainly based upon the stage of the disease so accurate imaging is crucial. SPECT/CT combines bone scan with high-resolution CT and can provide functional-anatomical images in a single stage. The purpose of this study was to assess the value of SPECT/CT in the management of OLT.

Multiple sclerosis in Hispanics: a study of clinical disease expression.

Background: Hispanics living with multiple sclerosis (MS) in the United States are not well defined.

Objective: To describe the clinical characteristics of MS among Hispanic Whites (HW) in Southern California with those of non-Hispanic Whites (NHW).

Methods: We performed a medical chart review to identify all cases of HW with MS (n = 125) who were treated at our institution during a 1-year period.

Influence of affinity and antigen internalization on the uptake and penetration of Anti-HER2 antibodies in solid tumors.

Antibody drugs are widely used in cancer therapy, but conditions to maximize tumor penetration and efficacy have yet to be fully elucidated. In this study, we investigated the impact of antibody binding affinity on tumor targeting and penetration with affinity variants that recognize the same epitope. Specifically, we compared four derivatives of the C6.

Endoplasmic reticulum stress, the unfolded protein response, and gene network modeling in antiestrogen resistant breast cancer.

Lack of understanding of endocrine resistance remains one of the major challenges for breast cancer researchers, clinicians, and patients. Current reductionist approaches to understanding the molecular signaling driving resistance have offered mostly incremental progress over the past 10 years. As the field of systems biology has begun to mature, the approaches and network modeling tools being developed and applied therein offer a different way to think about how molecular signaling and the regulation of critical cellular functions are integrated.

Photoreduction of carbon dioxide to carbon monoxide with hydrogen catalyzed by a rhenium(I) phenanthroline-polyoxometalate hybrid complex.

A phenanthroline ligand decorated at the 5,6-position with a 15-crown-5 ether was used to prepare a metalorganic-polyoxometalate hybrid complex Re(I)(L)(CO)(3)CH(3)CN-MHPW(12)O(40) (L = 15-crown-5-phenanthroline, M = Na(+), H(3)O(+)). X-ray diffraction, (1)H and (13)C NMR, ESI-MS, IR, and elemental analysis were used to characterize this complex. In the presence of Pt/C, the polyoxometalate moiety in Re(I)(L)(CO)(3)CH(3)CN-MHPW(12)O(40) can oxidize H(2) to two protons and two electrons which in the presence of visible light can catalyze the photoreduction of CO(2) to CO with H(2) as the reducing agent instead of the universally used amines as sacrificial reducing agents.

Targeted oxidation of Torpedo californica acetylcholinesterase by singlet oxygen.

The photosensitizer, methylene blue (MB), is a strong reversible inhibitor of Torpedo californica acetylcholinesterase (AChE) in the dark. Under illumination it causes irreversible inactivation. Loss of fluorescence of the singlet oxygen ((1)O(2)) trap, 9,10-dimethylanthracene, was retarded in the presence of AChE, and the rate of photo-inactivation was increased in the presence of D(2)O, indicating that inactivation was due to (1)O(2) generated by the photosensitizer.

[Acute psychotic disorders related to bupropion: review of the literature].

Rationale And Objectives: Bupropion, or amfebutamone, is an atypical antidepressant also used during tobacco cessation. From a structural standpoint, it resembles amphetamine drugs with psychostimulant effects, and endogenous monoamines. From a pharmacological standpoint, bupropion, and two of its most important active metabolites, inhibit dopamine and norepinephrine reuptake.

Synthetic lethal screen of an EGFR-centered network to improve targeted therapies.

Intrinsic and acquired cellular resistance factors limit the efficacy of most targeted cancer therapeutics. Synthetic lethal screens in lower eukaryotes suggest that networks of genes closely linked to therapeutic targets would be enriched for determinants of drug resistance. We developed a protein network centered on the epidermal growth factor receptor (EGFR), which is a validated cancer therapeutic target, and used small interfering RNA screening to comparatively probe this network for proteins that regulate the effectiveness of both EGFR-targeted agents and nonspecific cytotoxic agents.

Phase II and coagulation cascade biomarker study of bevacizumab with or without docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma.

Purpose: Treatment options are limited for advanced pancreatic cancer progressive after gemcitabine therapy. The vascular endothelial growth factor pathway is biologically important in pancreatic cancer, and docetaxel has modest antitumor activity. We evaluated the role of the anti-vascular endothelial growth factor antibody bevacizumab as second-line treatment for patients with metastatic pancreatic cancer.

Monoclonal antibodies: versatile platforms for cancer immunotherapy.

Antibodies are important therapeutic agents for cancer. Recently, it has become clear that antibodies possess several clinically relevant mechanisms of action. Many clinically useful antibodies can manipulate tumour-related signalling.

Vaccine prevention of cancer: can endogenous antigens be targeted?

This perspective on the report by Beatty et al. in this issue of the journal (beginning on page 438) discusses the prevention of cancer through vaccination strategies that target antigens associated with tumor promotion and progression. Such approaches were first developed for treating cancer.

De novo design of a non-natural fold for an iron-sulfur protein: alpha-helical coiled-coil with a four-iron four-sulfur cluster binding site in its central core.

Using a 'metal-first' approach, we computationally designed, prepared, and characterized a four-iron four-sulfur (Fe(4)S(4)) cluster protein with a non-natural alpha-helical coiled-coil fold. The novelty of this fold lies in the placement of a Fe(4)S(4) cluster within the hydrophobic core of a four-helix bundle, making it unique among previous iron-sulfur (FeS) protein designs, and different from known natural FeS proteins. The apoprotein, recombinantly expressed and purified from E.

Photochemical reduction of carbon dioxide catalyzed by a ruthenium-substituted polyoxometalate.

A polyoxometalate of the Keggin structure substituted with Ru(III), (6)Q(5)[Ru(III)(H(2)O)SiW(11)O(39)] in which (6)Q=(C(6)H(13))(4)N(+), catalyzed the photoreduction of CO(2) to CO with tertiary amines, preferentially Et(3)N, as reducing agents. A study of the coordination of CO(2) to (6)Q(5)[Ru(III)(H(2)O)SiW(11)O(39)] showed that 1) upon addition of CO(2) the UV/Vis spectrum changed, 2) a rhombic signal was obtained in the EPR spectrum (g(x)=2.146, g(y)=2.