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1.
Adv Gerontol ; 31(6): 887-891, 2018.
Article in Russian | MEDLINE | ID: mdl-30877818

ABSTRACT

For the purpose of systematization of the directions of rendering psychiatric help to pensioners of law-enforcement bodies (OVD) of the Russian Federation with mental disorders, the analysis of the existing normative legal acts regulating psychiatric examination of employees of Department of internal Affairs of the Russian Federation at dismissal on retirement and attachment on medical care in departmental healthcare institutions is carried out. It is shown that the provision of specialized psychiatric and psychotherapeutic assistance to pensioners of internal Affairs of the Russian Federation is carried out mainly in the municipal health care system, there is no monitoring of the mental state of pensioners of internal Affairs of the Russian Federation, including combatants with post-stress disorders. Within the framework of the project Of the concept of development of the psychiatric service of the Ministry of internal Affairs of Russia, it is proposed to systematize approaches to the organization of psychiatric care for pensioners of the Ministry of internal Affairs of the Russian Federation with mental disorders in the structure of departmental health care, with the improvement of the regulatory legal framework for the organization of psychiatric care, which will ensure the provision of high-quality psychiatric care.


Subject(s)
Mental Disorders/therapy , Mental Health Services/organization & administration , Pensions , Police/psychology , Humans , Retirement , Russia
2.
Child Care Health Dev ; 43(6): 854-860, 2017 11.
Article in English | MEDLINE | ID: mdl-28748578

ABSTRACT

BACKGROUND: Although it is estimated that half of all children with cerebral palsy also have comorbid intellectual disability, the domains of quality of life (QOL) important for these children are not well understood. The aim of this study was to identify important domains of QOL for these children and adolescents. METHODS: Due to the children's communication impairments, qualitative semi-structured interviews were conducted with 18 parents. The children (9 males) had a median age of 12 (range 7 to 17) years at interview and nearly two thirds were classified as Gross Motor Function Classification System IV or V. A grounded theory approach was used to identify domains of QOL. RESULTS: The 11 domains identified as important to QOL were physical health, body comfort, behaviour and emotion, communication, predictability and routine, movement and physical activity, nature and outdoors, variety of activity, independence and autonomy, social connectedness, and access to services. CONCLUSIONS: The domains of QOL that emerged from this study will be useful for professionals who support children with cerebral palsy and their families. They will also be important for developing a QOL instrument essential for informing the development of interventions and their monitoring and evaluation.


Subject(s)
Cerebral Palsy/rehabilitation , Disabled Children/rehabilitation , Intellectual Disability/rehabilitation , Quality of Life , Adolescent , Cerebral Palsy/psychology , Child , Communication , Disability Evaluation , Disabled Children/psychology , Female , Humans , Intellectual Disability/etiology , Intellectual Disability/psychology , Interpersonal Relations , Male , Psychometrics , Registries , Victoria
3.
Colorectal Dis ; 18(2): O51-60, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26708838

ABSTRACT

AIM: It is recognized that higher surgeon volume is associated with improved survival in colorectal cancer. However, there is a paucity of national studies that have evaluated the relationship between surgical specialization and survival. METHOD: We used the Surveillance, Epidemiology, and End Results Medicare cancer registry to examine the association between colorectal specialization (CRS) and disease-specific survival (DSS) between 2001 and 2009. A total of 21,432 colon cancer and 5893 rectal cancer patients who underwent elective surgical resection between 2001 and 2009 were evaluated. Univariate and multivariate Cox survival analysis was used to identify the association between surgical specialization and cancer-specific survival. RESULTS: Colorectal specialists performed 16.3% of the colon and 27% of the rectal resections. On univariate analysis, specialization was associated with improved survival in Stage II and Stage III colon cancer and Stage II rectal cancer. In multivariate analysis, however, CRS was associated with significantly improved DSS only in Stage II rectal cancer [hazard ratio (HR) 0.70, P = 0.03]. CRS was not significantly associated with DSS in either Stage I (colon HR 1.14, P = 0.39; rectal HR 0.1.26, P = 0.23) or Stage III (colon HR 1.06, P = 0.52; rectal HR 1.08, P = 0.55) disease. When analysis was limited to high volume surgeons only, the relationship between CRS and DSS was unchanged. CONCLUSIONS: CRS is associated with improved DSS following resection of Stage II rectal cancer. A combination of factors may contribute to long-term survival in these patients, including appropriate surgical technique, multidisciplinary treatment decisions and guideline-adherent surveillance. CRS probably contributes positively to these factors resulting in improved survival.


Subject(s)
Colectomy/mortality , Colonic Neoplasms/surgery , Colorectal Surgery/statistics & numerical data , Rectal Neoplasms/surgery , Specialization , Aged , Aged, 80 and over , Clinical Competence/statistics & numerical data , Colectomy/methods , Colonic Neoplasms/mortality , Colorectal Surgery/methods , Disease-Free Survival , Female , Humans , Male , Multivariate Analysis , Proportional Hazards Models , Rectal Neoplasms/mortality , Retrospective Studies
4.
Psychooncology ; 24(12): 1767-73, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25708116

ABSTRACT

OBJECTIVE: Most cancer patients desire information about care options at the end of life, including cardiopulmonary resuscitation (CPR). Communicating such care options can be challenging and is part of advance care planning (ACP). Our prior studies with video educational media produced data on patients' categoric preferences (yes/no/unsure) for CPR; however, the thematic underpinnings of these educated preferences in patients treated for advanced cancer aren't well known. METHODS: Qualitative thematic content analysis of participants' responses in a randomized trial of an educational video (V) or narrative (N) about CPR in patients with advanced gastrointestinal cancers. Responses were independently coded and categorized for thematic content by two reviewers. RESULTS: Of 54 study participants, 26 total (41% of V arm, 56% of N arm) articulated questions, comments, or both. Reviewer analyses demonstrated thematic consensus and resulted in seven distinct themes listed in decreasing order of prevalence: (a) ACP should be started early; (b) educational information about CPR affirmed participants' existing beliefs/knowledge/values about advanced illness; (c) participants were apprehensive about ACP but wanted to discuss it; (d) gaps in knowledge about ACP emerged; (e) CPR information was helpful/acceptable; (f) physicians should be involved in ACP; and (g) medical questions about critical illness arose. CONCLUSIONS: Findings identified that while sometimes difficult to discuss, advance care planning is desired, deemed helpful, and ideally begun early by clinicians, and that video education is an appropriate and affirming initiator of discussions. These themes are incorporated into our ongoing research on cancer patient-specific values and education about care options.


Subject(s)
Advance Care Planning , Cardiopulmonary Resuscitation/psychology , Neoplasms/therapy , Patient Education as Topic , Patient Participation/psychology , Patient Preference/psychology , Adult , Aged , Attitude to Health , Female , Humans , Male , Middle Aged
5.
J Small Anim Pract ; 55(6): 314-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24697570

ABSTRACT

OBJECTIVES: To assess the usefulness of clinical and clinicopathological parameters as prognostic markers of survival in dogs undergoing positive pressure ventilation. METHODS: Retrospective study of case records of 58 client-owned dogs undergoing positive pressure ventilation. Dogs were divided into two groups; inadequate oxygenation due to pulmonary parenchymal disease (Group 1) and inadequate ventilation (Group 2). RESULTS: Median duration of positive pressure ventilation was 30 (range 10 to 136) hours. Survival rate was 32% (19 dogs). Survivors were significantly younger (P<0·005) and had significantly higher (P<0·002) median PaO2 /FiO2 ratio at 4 to 12 hours postinitiation of positive pressure ventilation, and immediately before weaning (P<0·006) compared to non-survivors. A receiver operator characteristics analysis of PaO2 /FiO2 immediately before weaning as predictor of survival had an area under the curve of 0·76 (95% confidence interval 0·54 to 0·97), with optimal cut-off point of 252 mmHg, corresponding to a sensitivity and specificity of 0·80 and 0·79, respectively. The survival rates of dogs with PaO2 /FiO2 less than 200 mmHg at 4 to 12 hours postinitiation of positive pressure ventilation, or immediately before weaning were 15% (3/20 dogs) and 6% (1/16 dogs), respectively. CLINICAL SIGNIFICANCE: The PaO2 /FiO2 ratio is an early prognostic indicator of successful weaning in dogs undergoing positive pressure ventilation.


Subject(s)
Dog Diseases/therapy , Positive-Pressure Respiration/veterinary , Animals , Dog Diseases/diagnosis , Dog Diseases/mortality , Dogs , Female , Lung Diseases/mortality , Lung Diseases/therapy , Lung Diseases/veterinary , Male , Positive-Pressure Respiration/adverse effects , Positive-Pressure Respiration/methods , Positive-Pressure Respiration/mortality , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome , Ventilator Weaning/veterinary
6.
Nano Lett ; 14(3): 1196-201, 2014 Mar 12.
Article in English | MEDLINE | ID: mdl-24490665

ABSTRACT

The magnetic properties of molecular structures can be tailored by chemical synthesis or bottom-up assembly at the atomic scale. We used scanning tunneling microscopy to study charge and spin transfer in individual complexes of transition metals with the charge acceptor, tetracyanoethylene (TCNE). The complexes were formed on a thin insulator, Cu2N on Cu(100), by manipulation of individual atoms and molecules. The Cu2N layer decouples the complexes from Cu electron density, enabling direct imaging of the TCNE molecular orbitals as well as spin-flip inelastic electron tunneling spectroscopy. Results were obtained at low temperature down to 1 K and in magnetic fields up to 7 T in order to resolve splitting of spin states in the complexes. We also performed spin-polarized density functional theory calculations to compare with the experimental data. Our results indicate that charge transfer to TCNE leads to a change in spin magnitude, Kondo resonance, and magnetic anisotropy for the metal atoms.

7.
J R Coll Physicians Edinb ; 43(3): 215-21, 2013.
Article in English | MEDLINE | ID: mdl-24087799

ABSTRACT

OBJECTIVE: To describe the views of the chairs of Scottish health boards on the engagement of their boards with healthcare quality and to compare them with the views of the chairs of boards of English acute trusts. The focus of the Scottish Health Boards is on providing and commissioning care, while in England the acute trusts only provide care. METHODS: We mailed a questionnaire, based on one used in England, to the 14 health board chairs in NHS Scotland in January 2011. The results were compared with the results of a similar questionnaire given to English acute trust chairs in 2009. RESULTS: Most chairs in Scotland (67%) prioritised oversight of quality. Quality is considered at most Board meetings (92%), taking over 20% of time for 69% of chairs. Most boards have local quality targets and feedback quality data to staff. Compared with England, boards in Scotland meet less frequently and focus less on quality (shorter discussions, less frequent data review, fewer local targets) but they are more optimistic about their board's performance. CONCLUSIONS: Although most chairs of Scottish boards view quality as a priority, they pay less attention to it than chairs in England, possibly due to their additional role in commissioning care.


Subject(s)
Attitude of Health Personnel , Governing Board , Quality of Health Care , State Medicine/organization & administration , Clinical Governance , England , Scotland , State Medicine/standards , Surveys and Questionnaires
8.
Ann Oncol ; 23 Suppl 3: 43-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22628415

ABSTRACT

Palliative care is a rapidly growing subspecialty of medicine entailing expert and active assessment, evaluation and treatment of the physical, psychological, social and spiritual needs of patients and families with serious illnesses. It provides an added layer of support to the patient's regular medical care. As cancer is detected earlier and its treatments improve, palliative care is increasingly playing a vital role in the oncology population. Because of these advances in oncology, the role of palliative care services for such patients is actively evolving. Herein, we will highlight emerging paradigms in palliative care and attempt to delineate key education, research and policy areas that lie ahead for the field of palliative oncology. Despite the critical need for improving multi-faceted and multi-specialty symptom management and patient-physician communication, we will focus on the interface between palliative care and oncology specialists, a relationship that can lead to better overall patient care on all of these levels.


Subject(s)
Medical Oncology/methods , Neoplasms/psychology , Neoplasms/therapy , Palliative Care/methods , Communication , Humans , Medical Oncology/trends , Palliative Care/psychology , Palliative Care/trends
9.
Nanotechnology ; 22(49): 494007, 2011 Dec 09.
Article in English | MEDLINE | ID: mdl-22101439

ABSTRACT

Surface-associated communities of bacteria, called biofilms, pervade natural and anthropogenic environments. Mature biofilms are resistant to a wide range of antimicrobial treatments and therefore pose persistent pathogenic threats. The use of surface chemistry to inhibit biofilm growth has been found to only transiently affect initial attachment. In this work, we investigate the tunable effects of physical surface properties, including high-aspect-ratio (HAR) surface nanostructure arrays recently reported to induce long-range spontaneous spatial patterning of bacteria on the surface. The functional parameters and length scale regimes that control such artificial patterning for the rod-shaped pathogenic species Pseudomonas aeruginosa are elucidated through a combinatorial approach. We further report a crossover regime of biofilm growth on a HAR nanostructured surface versus the nanostructure effective stiffness. When the 'softness' of the hair-like nanoarray is increased beyond a threshold value, biofilm growth is inhibited as compared to a flat control surface. This result is consistent with the mechanoselective adhesion of bacteria to surfaces. Therefore by combining nanoarray-induced bacterial patterning and modulating the effective stiffness of the nanoarray--thus mimicking an extremely compliant flat surface--bacterial mechanoselective adhesion can be exploited to control and inhibit biofilm growth.


Subject(s)
Biofilms , Nanostructures/chemistry , Pseudomonas aeruginosa/physiology , Bacterial Adhesion , Elastic Modulus , Polymers/chemistry , Pseudomonas aeruginosa/cytology , Pseudomonas aeruginosa/growth & development , Surface Properties
10.
Phys Rev Lett ; 106(15): 156602, 2011 Apr 15.
Article in English | MEDLINE | ID: mdl-21568590

ABSTRACT

We report the successful extraction of spin-polarized current from the organic-based room temperature ferrimagnetic semiconductor V[TCNE](x) (x∼2, TCNE: tetracyanoethylene; T(C)∼400 K, E(G)∼0.5 eV, σ(300 K)∼10(-2) S/cm) and its subsequent injection into a GaAs/AlGaAs light-emitting diode. The spin current tracks the magnetization of V[TCNE](x∼2), is weakly temperature dependent, and exhibits heavy-hole-light-hole asymmetry. This result has implications for room temperature spintronics and the use of inorganic materials to probe spin physics in organic and molecular systems.

11.
Biochimie ; 92(12): 1839-46, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20709138

ABSTRACT

To block expression of NMDA receptor NR1 subunit, we injected into rat hippocampus a Herpes Simplex Virus type 1 derived vector bearing a sequence for NR1 antisense. RT-PCR assays with RNA from hippocampus of animals injected either with NR1 antisense vector, control vector or vehicle, showed an amplification signal compatible with NR1 antisense which could be attributed either to an endogenous NR1 antisense or to an artifact. RT-PCR was performed either with different primers or without primers in the RT, using RNA from different tissues. RNAse protection assay was carried out to characterize the amplified signal nature. Our results show that the template for the unexpected amplified fragment was NR1 mRNA currently expressed in nervous tissue. We considered this basal amplification of a mRNA in a RT-PCR assay as "background amplification". After background subtraction, a significant signal only remained when samples from NR1 antisense vector injected animals were used, demonstrating that this was the only source for NR1 antisense. Background amplification at RT in the absence of primers, can constitute a troubling factor in quantitative nucleic acid determination, leading to major interference, particularly when both sense and antisense sequences are present in the sample. Since RT introduced a significant background signal for every gene analyzed, we propose that RT must be always performed also without primers. Then, this signal should be identified, quantified and subtracted from the specific reaction amplification signal.


Subject(s)
DNA, Complementary/genetics , Hippocampus/metabolism , RNA, Antisense/genetics , Receptors, N-Methyl-D-Aspartate/genetics , Animals , DNA, Complementary/metabolism , Genetic Vectors/administration & dosage , Genetic Vectors/genetics , Herpesvirus 1, Human/genetics , Injections , Male , RNA, Antisense/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction
12.
Nat Mater ; 9(8): 638-42, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20639895

ABSTRACT

The new paradigm of electronics, 'spintronics', promises to extend the functionality of information storage and processing in conventional electronics. The principal spintronics device, the 'spin valve', consists of two magnetic layers decoupled by a spin-transporting spacer, which allows parallel (on) and antiparallel (off) alignment of the magnetizations (spins) of the two magnetic layers. The device resistance then depends on the spin alignment controlled by the external magnetic field. In pursuit of semiconductor spintronics, there have been intensive efforts devoted to develop room-temperature magnetic semiconductors and also to incorporate both inorganic semiconductors and carbon-based materials as the spin-transporting channels. Molecule/organic-based magnets, which allow chemical tuning of electronic and magnetic properties, are a promising new class of magnetic materials for future spintronic applications. Here, we report the realization of an organic-based magnet as an electron spin polarizer in the standard spintronics device geometry. A thin non-magnetic organic semiconductor layer and an epitaxial ferromagnetic oxide film were employed to form a hybrid magnetic tunnel junction. The results demonstrate the spin-polarizing nature of the organic-based magnetic semiconductor, vanadium(TCNE: tetracyanoethylene)(x) (x approximately 2; T(c) approximately 400 K), and its function as a spin injector/detector in hybrid magnetic multilayer devices.

13.
Resuscitation ; 80(10): 1197-203, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19631443

ABSTRACT

AIMS: A percutaneous left ventricular assist device has been shown to be able to perfuse cardiac and cerebral tissues during cardiac arrest and may be a useful supplement to current methods in resuscitation. We wished to assess device-assisted circulation during cardiac arrest with microspheres injections and continuous end-tidal CO(2) monitoring, and used cerebral microdialysis to detect ischaemia in the brain. METHODS: 12 anaesthetised pigs had microdialysis and pressure catheters implanted via craniotomy. The percutaneous assist device was deployed transfemorally. Ventricular fibrillation was induced by angioplasty-balloon occlusion of the left coronary artery. Cerebral microdialysis samples representing 0-20 and 20-40 min of cardiac arrest with assisted circulation were analysed for markers of cerebral injury (glucose, pyruvate, lactate, and glycerol). RESULTS: Microdialysis showed no ischaemic changes after 20 min of cardiac arrest (P=NS to Baseline for glucose, glycerol, lactate, pyruvate and lactate/pyruvate ratio) in subjects with maintained end-tidal CO(2) values above 1.3 kPa (10 mmHg). After 40 min only lactate showed a significant change compared to Baseline (P<0.05). Microspheres flow to the brain was 57% and myocardial flow was 72% compared to Baseline after 15 min (P<0.05). After 45 min flow declined to 22% and 40% of Baseline, respectively (P=NS vs. 15 min). CONCLUSIONS: A percutaneous left ventricular assist device may prevent ischaemic cerebral injury during cardiac arrest for a limited time. Cerebral injury and tissue perfusion were indicated by end-tidal CO(2).


Subject(s)
Brain Ischemia/prevention & control , Cerebrovascular Circulation , Heart Arrest/complications , Heart-Assist Devices , Ventricular Fibrillation/physiopathology , Acute Disease , Animals , Blood Flow Velocity , Brain Ischemia/etiology , Brain Ischemia/physiopathology , Cardiac Catheterization , Heart Arrest/physiopathology , Hemodynamics , Hemoglobins/analysis , Lactic Acid/blood , Microdialysis , Microspheres , Swine , Vascular Resistance , Ventricular Fibrillation/complications , Ventricular Fibrillation/therapy
14.
Gene Ther ; 16(6): 709-15, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19369969

ABSTRACT

The last two years have seen significant advances in our understanding of the cellular innate responses elicited or activated by the entry of amplicon particles, which may, in part, explain the transient nature of transgene expression often observed in cells infected with helper-free amplicon stocks. At the technological level, the most consistent progress has been in strategies to enhance the stability of transgene cassettes, either through integration into host chromosomes or through the conversion of the amplicon genome into a replication-competent extrachromosomal element.


Subject(s)
Gene Expression Regulation, Viral/physiology , Gene Silencing , Gene Transfer Techniques/trends , Genetic Vectors/genetics , Herpesvirus 1, Human/genetics , Immunity, Innate , Animals , Cell Cycle , Cell Line , Chromosomes, Artificial, Human , DNA, Recombinant/genetics , DNA, Viral/genetics , Dependovirus/genetics , Fibroblasts/immunology , Fibroblasts/virology , Genetic Engineering/methods , Genetic Engineering/trends , Genetic Vectors/physiology , Helper Viruses/genetics , Herpesvirus 1, Human/immunology , Herpesvirus 1, Human/physiology , Humans , Immediate-Early Proteins/physiology , Interferon Regulatory Factor-3 , Mice , Mice, Knockout , Models, Animal , Plasmids , Stem Cells/physiology , Transfection , Transgenes/genetics
15.
Phys Rev Lett ; 101(19): 197206, 2008 Nov 07.
Article in English | MEDLINE | ID: mdl-19113304

ABSTRACT

The 2D layered organic-based magnet [Fe(TCNE)(NCMe)2][FeCl4] (TCNE=tetracyanoethylene) exhibits a unique macroscopic magnetic bistability between the field-cooled and zero-field-cooled states, which cannot be explained by either superparamagnetic behavior or spin freezing due to spin glass order. This magnetic bistability is described through consideration of the ensemble of uncoupled 2D Ising layers and their magnetization reversal initiated by a field-induced nucleation of magnetic bubbles in individual layers. The bubble nucleation rate strongly depends on the external field and temperature resulting in anomalous magnetic relaxation.

17.
Phys Rev Lett ; 100(25): 257204, 2008 Jun 27.
Article in English | MEDLINE | ID: mdl-18643700

ABSTRACT

X-ray absorption spectroscopy (XAS) and magnetic circular dichroism (MCD) at the V L{2,3} and C and N K edges reveal bonding and backbonding interactions in films of the 400 K magnetic semiconductor V[TCNE]x approximately 2. In V spectra, d{xy}-like orbitals are modeled assuming V2+ in an octahedral ligand field, while d{z{2}} and d{x{2}-y{2}} orbitals involved in strong covalent sigma bonding cannot be modeled by atomic calculations. C and N MCD, and differences in XAS from neutral TCNE molecules, reveal spin-polarized molecular orbitals in V[TCNE]x approximately 2 associated with weaker pi bonding interactions that yield its novel properties.

18.
Phys Rev Lett ; 100(6): 067201, 2008 Feb 15.
Article in English | MEDLINE | ID: mdl-18352505

ABSTRACT

We report that organic semiconductors such as alpha-sexithiophene (alpha-6T) have magnetoresistance (MR) with unexpected sign changes; depending on applied voltage, temperature, and layer thickness, the resistance may either increase or decrease upon application of a small magnetic field (<100 mT). We propose that MR and the inversion of MR are due to the role of hyperfine interaction in a magnetic field, as illustrated by the recombination-limited regime.

19.
Handb Exp Pharmacol ; (181): 291-328, 2008.
Article in English | MEDLINE | ID: mdl-18071951

ABSTRACT

This chapter describes the generation of novel reagents for the treatment of cancer using fusion proteins constructed with natural ligands of the immune system. Immunotherapy is a powerful therapeutic modality that has not been fully harnessed for the treatment of cancer. We and others have hypothesized that if the proper immunoregulatory ligands can be targeted to the tumor, an effective immune response can be mounted to treat both established primary tumors and distant metastatic lesions. Though it is generally believed that immunotherapy has the potential to treat only residual disease, we offer evidence that this approach can, by itself, destroy large tumor masses and produce lasting remissions of experimental solid tumors. From these studies, three major classes of immune activators, namely, cytokines, chemokines, and costimulatory molecules, have been shown to generate antitumor responses in animal models. In addition, the reversal of immune tolerance by the deletion of T regulatory (Treg) cells has been shown to be equally important for effective immunotherapy. In an attempt to identify reagents that can provide an enhanced immune stimulation and treatment of cancer, our laboratory has developed a novel monoclonal antibody targeting approach, designated Tumor Necrosis Therapy (TNT), which utilizes stable intracellular antigens present in all cell types but which are only accessible in dead and/or dying cells. Since tumors contain necrotic and degenerating regions that account for 30-80% of the tumor mass, this targeting approach can be used to deliver therapeutic reagents to the core of tumors, a site abundant in tumor antigens. In our first set of reagents, a panel of cytokine fusion proteins was genetically engineered using monoclonal antibody chimeric TNT-3 (chTNT-3) directed against necrotic regions of tumors (single-stranded DNA) fused with IL-2, or GM-CSF, or TNFalphaa, or IFNgamma. Tested against different solid tumors, these reagents were found to mount an effective although transient immune response to tumor especially when used in combination. To improve upon these results, additional chTNT-3 fusion proteins using the liver-expression chemokine (LEC) and the costimulatory molecule B7.1 were constructed. Both of these reagents were found to work significantly better than the above cytokine fusion proteins due to their ability to stimulate multiple arms of the immune system deemed useful for cancer immunotherapy. Finally, the Tumor Necrosis Factor Superfamily (TNFSF) gene DC137L was used to generate chTNT-3 antibody (targeted) and soluble Fc (untargeted) fusion proteins. When used alone, both forms of costimulatory fusion proteins were found to produce in a s dose-dependent manner, complete regression of murine solid tumors. Evidence is presented to show that Treg cells play an important role in suppressing antitumor immunity since the deletion of these cells, when used in combination with LEC or costimulatory fusion proteins, produced profound and effective treatment with sustained memory. It is hoped that these data will further the preclinical development of soluble Fc and antibody based fusion proteins fro the immunotherapy of cancer.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Chemokines/therapeutic use , Cytokines/therapeutic use , Immunotherapy/methods , Neoplasms/drug therapy , Animals , B7-1 Antigen/immunology , B7-1 Antigen/therapeutic use , Chemokines/immunology , Cytokines/immunology , Humans , Ligands , Neoplasms/immunology , Recombinant Fusion Proteins/therapeutic use , T-Lymphocytes, Regulatory/drug effects , Tumor Escape , Tumor Necrosis Factors/immunology , Tumor Necrosis Factors/therapeutic use
20.
Phys Rev Lett ; 99(15): 157205, 2007 Oct 12.
Article in English | MEDLINE | ID: mdl-17995210

ABSTRACT

The V(TCNE){x}, x approximately 2 is an organic-based amorphous ferrimagnet, whose magnetic behavior is significantly affected in the low field regime by the random magnetic anisotropy. It was determined that this material has thermally reversible persistent change in both magnetization and conductivity driven by the optical excitation. Here, we report results of a ferrimagnetic resonance study of the photoinduced magnetism in V(TCNE){x} film. Upon optical excitation (lambda approximately 457.9 nm), the ferrimagnetic resonance spectra display substantial changes in their linewidths and line shifts, which reflect a substantial increase in the random magnetic anistropy. The results reflect the role of magnetic anisotropy in disordered magnets and suggest a novel mechanism of photoinduced magnetism in V(TCNE){x} induced by the increased structural disorder in the system.

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