Mass Spectrometry-Based Protein Footprinting Defines the Binding Pocket of Crotonylated H3K14 in the PHD1 Domain of BAF45D within the BAF Chromatin Remodeling Complex.

The BRG-/BRM-associated factor (BAF) chromatin remodeling complex is a central actor in transcription. One mechanism by which BAF affects gene expression is via its various histone mark readers, including double plant homeodomains (DPF), located in the BAF45D subunit. DPF domains recognize lysine acetyl and acylations, including crotonylation, localized at promoters and enhancers.

Rational Control of Poliovirus RNA-Dependent RNA Polymerase Fidelity by Modulating Motif-D Loop Conformational Dynamics.

The conserved structural motif D is an important determinant of the speed and fidelity of viral RNA-dependent RNA polymerases (RdRps). Structural and computational studies have suggested that conformational changes in the motif-D loop that help to reposition the catalytic lysine represent critical steps in nucleotide selection and incorporation. Conformations of the motif-D loop in the poliovirus RdRp are likely controlled in part by noncovalent interactions involving the motif-D residue Glu364.

Development of a self-assembling protein nanoparticle vaccine targeting Plasmodium falciparum Circumsporozoite Protein delivered in three Army Liposome Formulation adjuvants.

We have developed FMP014, a vaccine candidate against Plasmodium falciparum malaria, which is comprised of 60 identical monomer protein chains that form an icosahedral shaped self-assembling protein nanoparticle (SAPN). Each monomer contains selected P. falciparum Circumsporozoite Protein (PfCSP) CD4+ and CD8+ epitopes, universal T epitopes, portions of the α-TSR domain, and 6 repeats of the NANP motifs of the PfCSP.

Triphosphate Reorientation of the Incoming Nucleotide as a Fidelity Checkpoint in Viral RNA-dependent RNA Polymerases.

The nucleotide incorporation fidelity of the viral RNA-dependent RNA polymerase (RdRp) is important for maintaining functional genetic information but, at the same time, is also important for generating sufficient genetic diversity to escape the bottlenecks of the host's antiviral response. We have previously shown that the structural dynamics of the motif D loop are closely related to nucleotide discrimination. Previous studies have also suggested that there is a reorientation of the triphosphate of the incoming nucleotide, which is essential before nucleophilic attack from the primer RNA 3'-hydroxyl.

Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase.

The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp).

RAHelp: an online intervention for individuals with rheumatoid arthritis.

Objective: To test an intervention for improving self-management in rheumatoid arthritis (RA) using an online, cognitive-behavioral, self-management group program (RAHelp), with weekly telephone support.

Methods: A 2-group, randomized study design was used to compare an intervention for RA versus a waiting-list control condition. The intervention used a secure web site (RAHelp.

Online self-management in rheumatoid arthritis: a patient-centered model application.

Objective: The aim of this study was to describe the online transformation of an empirically validated, clinic-based, self-management (SM) program for rheumatoid arthritis.

Materials And Methods: A cognitive-behavioral framework served as the theoretical basis for the intervention. As with the clinic-based approach, the psychoeducational program included educational modules, weekly homework assignments, and self-evaluation.

Social interactions in an online self-management program for rheumatoid arthritis.

Objective: To evaluate social interactions among individuals with rheumatoid arthritis (RA), participating in an empirically based, cognitive-behavioural, self-management (SM), and peer-support program, delivered in an online format.

Methods: Thirty individuals with RA were recruited online. Subjects were a subset of participants in the treatment arm of a waiting-list controlled study testing the effectiveness of a 10-week, online, SM education and peer support program.

IL-10 does not play a role in cutaneous Photofrin photodynamic therapy-induced suppression of the contact hypersensitivity response.

Photodynamic therapy (PDT) treatment of both malignant and benign skin diseases has proven to be effective, and its use is increasing worldwide. However, preclinical studies using murine models have shown that PDT of the skin inhibits cell-mediated immune reactions, as measured by the suppression of the contact hypersensitivity (CHS) reaction. We have previously demonstrated that PDT enhances IL-10 expression in treated skin, and that the kinetics of induction of IL-10 is similar to the kinetics of suppression of systemic CHS reactions by cutaneous PDT.

Characteristics of the immunosuppression induced by cutaneous photodynamic therapy: persistence, antigen specificity and cell type involved.

Relatively little is known about the immunosuppression induced in mice which have received cutaneous photodynamic therapy (PDT). Consequently, experiments were undertaken using mice which received dorsal PDT using Photofrin as the photosensitizer in an attempt to characterize the overall nature of the immunosuppression. Photoirradiation of mice at various times after injection indicated there was no correlation between photosensitivity and immunosuppression.

The anatomic site of photodynamic therapy is a determinant for immunosuppression in a murine model.

The role of the irradiation site in the induction of suppression of the contact hypersensitivity (CHS) response following photodynamic therapy (PDT) was examined in a murine model. Laser irradiation on the flanks of nontumor-bearing Photofrin-injected mice caused suppression of the CHS response. If the irradiation was conducted on a subcutaneously implanted foil disc on the flank no immunosuppression occurred, indicating that no suppressive factor(s) of sufficient quantity to cause suppression was released from the skin, but rather irradiation of internal organs was the cause.

Altered expression of interleukin 6 and interleukin 10 as a result of photodynamic therapy in vivo.

Photodynamic therapy (PDT), which can effectively destroy malignant tissue, also induces a complex immune response that potentiates antitumor immunity but also inhibits skin contact hypersensitivity (CHS) and prolongs skin graft survival. The underlying mechanisms responsible for these effects are poorly understood but are likely to involve mediation by cytokines. We demonstrate in a BALB/c mouse model that PDT delivered to normal and tumor tissue in vivo causes marked changes in the expression of cytokines interleukin (IL)-6 and IL-10 but not tumor necrosis factor alpha.

Duplex ultrasonography to diagnose failing arterial prosthetic grafts.

Background: Although several reports have documented the usefulness of a surveillance program with duplex ultrasonography (DU) to diagnose failing autologous vein bypasses, the effectiveness of DU to detect failing arterial prosthetic grafts has not been confirmed. We attempted to determine whether our program, which included DU and other noninvasive techniques (NonDU), was useful for this purpose.

Methods: Between July 1, 1991, and September 30, 1994, 85 prosthetic bypasses in 59 patients performed for lower extremity ischemia were entered into a graft surveillance protocol.

Safety and cost-efficiency of 24-hour hospitalization for carotid endarterectomy.

The safety and cost savings of carotid endarterectomy (CEA) were determined with guidelines developed after vascular "critical pathways" were implemented. Using these guidelines, our goal was to admit patients the day of surgery and to discharge them the next morning. Morbidity, mortality, readmission rates, same-day admissions, duration of stay, and hospital costs were compared between patients undergoing CEA who were electively admitted between September 1, 1992 and August 31, 1993 (group 1) and January 1, 1994 and March 31, 1995 (group 2).

Impact of clinical pathways on hospital costs and early outcome after major vascular surgery.

Purpose: The purpose of this study was to determine whether major vascular surgery could be performed safely and with significant hospital cost savings by decreasing length of stay and implementation of vascular clinical pathways.

Methods: Morbidity, mortality, readmission rates, same-day admissions, length of stay, and hospital costs were compared between patients who were electively admitted between September 1, 1992, and August 30, 1993 (group 1), and January 1 to December 31, 1994 (group 2), for extracranial, infrarenal abdominal aortic, and lower extremity arterial surgery. For group 2 patients, vascular critical pathways were instituted, a dedicated vascular ward was established, and outpatient preoperative arteriography and anesthesiology-cardiology evaluations were performed.

The use of tetrazolium salts to determine sites of damage to the mitochondrial electron transport chain in intact cells following in vitro photodynamic therapy with Photofrin II.

A method is described utilizing the tetrazolium salts neotetrazolium chloride (NTC), triphenyltetrazolium chloride (TTC), C,N-diphenyl-N'-4,5-dimethylthiazol-2-yltetrazolium bromide (MTT) and various substrates to elucidate damage to the mitochondrial electron transport chain of intact cells following in vitro photodynamic therapy (PDT). Using this methodology, a portion of the dark toxicity manifested by Photofrin II (PII) was found to occur prior to entry of electrons into the transport chain through Complex I, as evidenced by the fact that the inhibition of MTT reduction was reversible by the addition of malic acid to the culture media. A second site of dark toxicity was found to be Complex IV (cytochrome oxidase).

Death and adverse cardiac events after carotid endarterectomy.

Purpose: This study evaluated operative mortality rate and adverse cardiac events after carotid endarterectomy. Efficacy of preoperative cardiac evaluation was studied and stroke mortality rate was determined.

Methods: This was a retrospective review of 562 patients undergoing carotid endarterectomy at a 740-bed community hospital.

Laparoscopic colectomy: at what cost?

The purpose of this study was to compare laparoscopic to open colectomy with respect to: 1) morbidity and mortality, 2) adequacy of resection for cancer (margins and number of nodes), 3) operative time, 4) postoperative time for tolerating diet and discharge, and 5) total hospital charges. A historical control group of open colon surgery patients was used. Laparoscopic colectomy was completed in 18/24 patients and 6 were converted to open colectomy.

Nurse characteristics and professional autonomy.

Relationships between selected demographic characteristics and professional nursing autonomy were examined. Identification of such relationships can strengthen development of the professional nursing role. Usable responses were returned by 542 RNs in a random sample of 2,000 nurses from four states.

Cutaneous photosensitizing and immunosuppressive effects of a series of tumor localizing porphyrins.

A series of tumor localizing porphyrins was evaluated with respect to their ability to elicit cutaneous photosensitivity and systemic immunosuppression, two of the most common side effects associated with photodynamic therapy. Using the murine ear swelling response as an indicator, it was found that all the non-metalloporphyrins caused cutaneous photosensitization. Immunosuppressive effects were noted using hematoporphyrin derivative (HPD) and meso-tetra(4-sulfonatophenyl)porphine if sensitization occurred immediately after photoirradiation, but none were evident using Photofrin II (PII) or meso-tetra(4-carboxyphenyl)porphine (TCPP).

Bilateral femoral nerve neuropathy following blunt trauma. Case report.

A unique case of bilateral compressive injury of the femoral nerves is reported in a 19-year-old man. Traumatic femoral nerve neuropathy following operative injury, penetrating injury, anticoagulant therapy with hemorrhage, and stretch injury has been described previously, and the literature concerning this unusual clinical problem is reviewed. Bilateral traumatic femoral nerve neuropathy resulting from compressive injury has not been previously reported.

A comparative study of manganese meso-sulfonatophenyl porphyrins: contrast-enhancing agents for tumors.

Four manganese meso-sulfonatophenyl porphyrins were prepared, characterized and investigated for their potential as tumor-specific MRI contrast-enhancing agents in mice bearing subcutaneous implants of a mammary carcinoma (SMT-F). The trisulfonated tetraphenyl porphyrin, MnTPPS3 presented the most favorable profile: bio-distribution, tumor concentration and tumor relaxivity, when compared at 24 hr postinjection. Imaging experiments revealed that a time-dependent delineation of tumor morphology occurs in response to MnTPPS3 that appears to correlate with necrotic regions of the tumor.

The effect of photodynamic therapy (PDT) on glucose levels within the SMT-F mouse tumor.

Tumor glucose levels were assessed at various times following in vivo photodynamic therapy (PDT) and compared to levels following induction of anoxia in mice bearing the SMT-F tumor. Uptake of 2-deoxy-D glucose by isolated tumor cells was not altered following in vivo PDT. Tumor glucose levels following PDT were found to decline in a similar albeit slower manner to those found under anoxic conditions for 40 minutes and thereafter they declined at a greater rate.