Confronting the avian influenza threat: vaccine development for a potential pandemic.

Sporadic human infection with avian influenza viruses has raised concern that reassortment between human and avian subtypes could generate viruses of pandemic potential. Vaccination is the principal means to combat the impact of influenza. During an influenza pandemic the immune status of the population would differ from that which exists during interpandemic periods.

Efficient construction of the securine A carbon skeleton.

Securamine A is a structurally intriguing alkaloid possessing a pyrroloindole core joined via a modified isoprene subunit to a functionalized imidazole ring. Recent synthetic efforts in this laboratory have resulted in the efficient construction of key lactone 36, which undergoes tandem azide reduction/ring expansion to macrolactam 37. Macrolactam 37 possesses the complete macrocyclic core of securamine A.

MR imaging of newborns by using an MR-compatible incubator with integrated radiofrequency coils: initial experience.

To meet the needs of term and preterm neonates undergoing magnetic resonance (MR) imaging, an MR-compatible incubator with air, temperature, and humidity regulators and integrated radiofrequency coils was evaluated. Nine brain, two cardiac, and two pelvic examinations were performed by using a 1.5-T clinical MR imaging unit.

Stenting of the mainstem bronchus in children: a word of caution.

We present two patients with critical hemorrhage following expandable metallic stenting of the left mainstem bronchus in children. Stent migration with erosion into a bronchial artery leading to mycotic pseudoaneurysm formation and overwhelming pulmonary hemorrhage occurred in both patients. One patient died from uncontrollable hemoptysis.

Comparison of environmental scanning electron microscopy with high vacuum scanning electron microscopy as applied to the assessment of cell morphology.

The efficacy of conventional high vacuum scanning electron microscopy (SEM), environmental SEM (ESEM), and confocal laser scanning microscopy techniques in the assessment of cell-material interactions is compared. Specific attention is given to the application of these techniques in the assessment of the early morphological response of human osteoblast-like cells cultured on titanium dioxide. The processing of cells cultured for conventional high vacuum SEM leads to the loss of morphological features that are retained when using ESEM.

Total synthesis of (+/-)-kalihinol C.

The total synthesis of kalihinol C, a bis-isonitrile marine diterpenoid isolated from Acanthella sp., is reported. The decalin framework was established via an intramolecular Diels-Alder cycloaddition and subsequently functionalized through a series of substrate-controlled diastereoselective transformations to install the tertiary isonitrile, beta-hydroxy isonitrile, and pendant tetrahydrofuranyl ring.

Energy substrate requirements of rat retinal pigmented epithelial cells in culture: relative importance of glucose, amino acids, and monocarboxylates.

Purpose: To determine the metabolic conditions that provide maintenance of viability for cultured rat RPE cells and to determine whether monocarboxylates such as lactate or pyruvate, which are known to exist at high concentrations in the subretinal space, can provide an alternative energy source to maintain cells when other nutritive supplies are limited.

Methods: Cultured rat RPE cells (passage 2-4), in the absence of serum, were subjected to different metabolic challenges relating to glucose, amino acid, or oxygen deprivation. Lactate or pyruvate was added to some cells in each instance to determine whether cells could be maintained by using these substances as fuel sources for metabolic reactions.

Mimicking liver iron overload using liposomal ferritin preparations.

Close monitoring of liver iron content is necessary to prevent iron overload in transfusion-dependent anemias. Liver biopsy remains the gold standard; however, MRI potentially offers a noninvasive alternative. Iron metabolism and storage is complicated and tissue/disease-specific.

A clue to the therapy of neurofibromatosis type 2: NF2/merlin is a PAK1 inhibitor.

Background: Neurofibromatosis type 2 is a group of tumors caused by loss-of-function mutations of a tumor suppressor gene encoding NF2/merlin. Development of chemotherapeutics for this disease, which often threatens the life of young children, has been hampered by a limited information on the signaling function of NF2. NF2 can inhibit Ras-induced malignant transformation.

Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones.

The molecular basis of mechanosensory transduction by primary sensory neurones remains poorly understood. Amongst candidate transducer molecules are members of the acid-sensing ion channel (ASIC) family; nerve fibre recordings have shown ASIC2 and ASIC3 null mutants have aberrant responses to suprathreshold mechanical stimuli. Using the neuronal cell body as a model of the sensory terminal we investigated if ASIC2 or 3 contributed to mechanically activated currents in dorsal root ganglion (DRG) neurones.

Retinal ischemia: mechanisms of damage and potential therapeutic strategies.

Retinal ischemia is a common cause of visual impairment and blindness. At the cellular level, ischemic retinal injury consists of a self-reinforcing destructive cascade involving neuronal depolarisation, calcium influx and oxidative stress initiated by energy failure and increased glutamatergic stimulation. There is a cell-specific sensitivity to ischemic injury which may reflect variability in the balance of excitatory and inhibitory neurotransmitter receptors on a given cell.

Activation/deactivation of acetylcholinesterase by H2O2: more evidence for oxidative stress in vitiligo.

Previously it has been demonstrated that the human epidermis synthesises and degrades acetylcholine and expresses both muscarinic and nicotinic receptors. These cholinergic systems have been implicated in the development of the epidermal calcium gradient and differentiation in normal healthy skin. In vitiligo severe oxidative stress occurs in the epidermis of these patients with accumulation of H2O2 in the 10(-3)M range together with a decrease in catalase expression/activity due to deactivation of the enzyme active site.

Bowel necrosis caused by water in jejunal feeding.

Background: Fifteen reports of bowel necrosis in patients receiving jejunal feeding have been reported. Etiology remains unexplained.

Methods: A patient with a 60% burn receiving jejunostomy tube feeding developed hypernatremia and was given distilled water in the jejunum, 400 mL every 2 hours.

Identification of binding domains in the sodium channel Na(V)1.8 intracellular N-terminal region and annexin II light chain p11.

The interaction of p11 (annexin II light chain) with the N-terminal domain of Na(V)1.8, a tetrodotoxin-resistant sodium channel, is essential for the functional expression of the channel. Here we show that p11 binds to Na(V)1.

Characterization of common genetic variants in cathepsin K and testing for association with bone mineral density in a large cohort of perimenopausal women from Scotland.

Unlabelled: BMD values in approximately 3000 perimenopausal Scottish women were adjusted by regression to identify and account for nongenetic factors. Adjusted BMD values were not associated with simple tandem repeat (STR) markers or single nucleotide polymorphisms (SNPs) at the Cathepsin K (CTSK) locus. We present a thorough analysis of common CTSK polymorphisms and genetic relatedness among CTSK haplotypes.

The effect of retinal ganglion cell injury on light-induced photoreceptor degeneration.

Purpose: To determine the effect of optic nerve transection (ONT) and excitotoxic retinal ganglion cell (RGC) injury on light-induced photoreceptor degeneration.

Methods: Age- and sex-matched rats underwent unilateral ONT or received intravitreal injections of N-methyl-D-aspartate (NMDA). The fellow eye received sham treatment, and 7 or 21 days later each eye was subjected to an intense photic injury.

Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99 (H9N2) vaccine in healthy adults: phase I randomised trial.

Background: In 1999, avian influenza A/Hong Kong/1073/99 (H9N2) virus emerged as a pandemic threat to human beings. We aimed to assess safety, tolerability, and antigenicity of whole virus and subunit H9N2 vaccines in healthy volunteers.

Methods: In a phase I randomised trial we randomly assigned 60 participants to whole virus or subunit H9N2 vaccine.

PAK is essential for RAS-induced upregulation of cyclin D1 during the G1 to S transition.

Oncogenic RAS mutants such as v-Ha-RAS induce cell cycling, in particular the G1 to S transition, by upregulating cyclin D1 and downregulating p27, an inhibitor for cyclin-dependent kinases (CDKs). PI-3 kinase appears to be involved in the regulation of both cyclin D1 and p27. In this report, using two distinct inhibitors specific for PAK1-3 (CEP-1347 and WR-PAK18), we present the first evidence indicating that the PIX/Rac/CDC42-dependent Ser/Thr kinases PAK1-3, acting downstream of PI-3 kinase and upstream of the Raf/MEK/ERKs kinase cascade, is essential for RAS-induced upregulation of cyclin D1, but not downregulation of p27.

Oestrogenic compounds and oxidative stress (in human sperm and lymphocytes in the Comet assay).

Reactive oxygen species (ROS) are produced by a wide variety of chemicals and physiological processes in which enzymes catalyse the transfer of electrons from a substrate to molecular oxygen. The immediate products of such reactions, superoxide anion radicals and hydrogen peroxide can be metabolised by enzymes such as superoxide dismutase (SOD) and catalase (CAT), respectively, and depending on its concentration by Vitamin C (Vit C). Under certain circumstances the ROS form highly reactive hydroxyl radicals.

Influenza.

Although most influenza infections are self-limited, few other diseases exert such a huge toll of suffering and economic loss. Despite the importance of influenza, there had been, until recently, little advance in its control since amantadine was licensed almost 40 years ago. During the past decade, evidence has accrued on the protection afforded by inactivated vaccines and the safety and efficacy in children of live influenza-virus vaccines.

Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease.

Cardiac T2* (magnetic resonance imaging relaxation parameter) is abnormally low in approximately 40% of adults with thalassemia major (TM), suggesting myocardial iron deposition, but it is unknown at what age this occurs. To address this question, we measured cardiac T2* and function in 19 young patients (aged 7-26 years) with TM as well as 17 patients receiving long-term transfusions for sickle cell anemia (SCA) matched for age, sex, and liver iron content. Cardiac T2* was normal in all of the SCA patients but was low (high iron) in 8 of 19 TM patients.

Superiority of 3D wavelet-packet denoising in MR microscopy.

Three dimensional Magnetic Resonance Imaging (MRI) datasets are becoming increasingly important in clinical and research applications because of their inherent signal to noise (SNR) advantages, high resolution and isotropic voxels. Despite SNR advantages, some 3D acquisitions may be SNR-limited, particularly in MR microscopy. Historically, both classic filtering and wavelet-based denoising techniques have been performed on a slice-by-slice basis.

Zinc and energy requirements in induction of oxidative stress to retinal pigmented epithelial cells.

In age-related macular degeneration (AMD), retinal pigmented epithelium (RPE) cells are believed to be detrimentally affected. It is thought that zinc may play a part in this process. In the past, therefore, zinc supplementation has been suggested as a treatment for AMD.

Preparation of a standardized, efficacious agricultural H5N3 vaccine by reverse genetics.

Options for the control of emerging and reemerging H5N1 influenza viruses include improvements in biosecurity and the use of inactivated vaccines. Commercially available H5N2 influenza vaccine prevents disease signs and reduces virus load but does not completely prevent virus shedding after challenge with H5N1 virus. By using reverse genetics, we prepared an H5N3 vaccine whose hemagglutinin is 99.