Amplification of a SV40 T antigen transgene is associated with sarcomagenesis in mice

Transgenic mice harboring simian virus 40 large T antigen (Tag) gene fused to an erythroid-specific enhancer developed soft tissue sarcomas which expressed very high levels of T antigen. The Tag expression was not detectable in the animals' non-transformed tissues. While mice bearing several copies of the transgene developed tumors at an early age of 4-6 months, those with a single copy had a delayed onset of 10-16 months, and DNA analysis of their tumors showed amplification of the Tag transgene. Amplification of a Tag transgene has also been described previously in brain tumors. Our studies demonstrate that Tag transgene amplification is not restricted to a particular construct or a single tumor type. Therefore, this may be a general mechanism for Tag-mediated carcinogenesis, and our transgenic mouse system can be useful for elucidating the mechanisms that govern the amplification process of Tag sequences in vivo.     

Subtype and sequence analysis of the C2-V3 region of gp120 genes among HIV-1 strains in Hubei province

Eight (14 per cent) out of 57 consecutive cerebral malaria patients (all < 5 years old) were malnourished, including one with marasmus and another recovering from kwashiorkor. This was significantly lower than among other paediatric patients in the same children's emergency ward (112/319, i.e. 35 per cent, P < 0.01). Poor outcomes (death or recovery with neurological deficits) were commoner in the malnourished group (4/8) than the well nourished group (7/49) (P = 0.037, Fisher's exact test). Malnourished children should receive malaria chemoprophylaxis during nutritional rehabilitation.     

Phosphorylation of elongation factor 1 and ribosomal protein S6 by multipotential S6 kinase and insulin stimulation of translational elongation

Stimulation of protein synthesis in response to insulin is concomitant with increased phosphorylation of initiation factors 4B and 4G and ribosomal protein S6 (Morley, S. J., and Traugh, J. A. (1993) Biochimie 75, 985-989) and is due at least in part to multipotential S6 kinase. When elongation factor 1 (EF-1) from rabbit reticulocytes was examined as substrate for multipotential S6 kinase, up to 1 mol/mol of phosphate was incorporated into the alpha, beta, and delta subunits. Phosphorylation of EF-1 resulted in a 2-2. 6-fold stimulation of EF-1 activity, as measured by poly(U)-directed polyphenylalanine synthesis. The rate of elongation was also stimulated by approximately 2-fold with 80 S ribosomes phosphorylated on S6 by multipotential S6 kinase. When the rates of elongation in extracts from serum-fed 3T3-L1 cells and cells serum-deprived for 1.5 h were compared, a 40% decrease was observed upon serum deprivation. The addition of insulin to serum-deprived cells for 15 min stimulated elongation to a rate equivalent to that of serum-fed cells. Similar results were obtained with partially purified EF-1, with both EF-1 and ribosomes contributing to stimulation of elongation. These data are consistent with a ribosomal transit time of 3.2 min for serum-deprived cells and 1.6 min following the addition of insulin for 15 min. Taken together, the data suggest that insulin stimulation involves coordinate regulation of EF-1 and ribosomes through phosphorylation by multipotential S6 kinase.     

Immunochemical differences between glucocorticoid receptors from corticoid-sensitive and -resistant malignant lymphocytes

We have explored the possibility of using antibodies against purified rat liver glucocorticoid receptors to study the immunochemical properties of glucocorticoid receptors from murine and human malignant lymphocytes. For this purpose, purified immune immunoglobulin G was covalently linked to Sepharose CL-4B. We then examined the ability of the affinity gel to recognize cytosolic [3H]triamcinolone acetonide-receptor complexes from the corticoid-sensitive (CS) and -resistant strains of mouse lymphoma P1798, from CS lymphocytes of patients with chronic lymphatic leukemia, and from a CS clone of human leukemic lymphoblasts in tissue culture (CH6). Mouse thymus was used as a source of glucocorticoid receptor from normal CS lymphocytes. Whereas the immunoaffinity column retained 70 to 84% of the 58- to 62-A (Stokes radius) [3H]triamcinolone acetonide-receptor complexes characteristic of the CS mouse and human lymphocytes, it failed to recognize the 27- to 28-A (Stokes radius) glucocorticoid receptor present in corticoid-resistant mouse lymphoma P1798 cells. Therefore, under appropriate experimental conditions, it was possible to demonstrate cross-reactivity between the antiserum against rat liver glucocorticoid receptor and the 58- to 62-A (Stokes radius) glucocorticoid receptor from species as diverse as mouse and humans.     

Endoscopic Nd:YAG laser treatment of inoperable lower gastrointestinal cancer

Many patients with colorectal cancer are not amenable to curative resection at the time of presentation. Nevertheless, palliative resection still remains as the treatment of choice in the majority of patients. A small group of patients that are poor candidates for surgical resection may benefit from some non-surgical palliative procedures to relieve their symptoms. Electrocoagulation, cryosurgery and radiotherapy are some of the non-surgical procedure used and they are associated with high morbidity and mortality. The use of Neodymium: Yttrium-Aluminium-Garnet (Nd:YAG) laser photoablation to palliate patients with advanced colorectal carcinoma is well documented. It is associated with relatively low morbidity and perioperative mortality. It requires no anaesthesia and is the only non-surgical procedure that can be safely carried out above the peritoneal reflection. Nd:YAG laser had been used in some centres as a preresectional procedure in patient presenting with high grade obstruction. It allows proper bowel preparation followed by primary excision and anastomosis. As a palliative procedure, most patients showed rapid improvement in obstructive symptoms, bleeding and rectal discharge. The size of the lesion and circumferential extent of the tumour base correlate well with the response rate. Most patients remained asymptomatic before they succumb to the advanced disease. In our series, good palliation of obstructive symptoms was achieved in all obstructive cases with one laser treatment, bleeding tumours required an average of two sessions for complete haemostasis. In conclusion, Nd:YAG laser therapy is a safe and efficacious means for palliation of obstructive symptoms and bleeding in advanced rectal carcinoma.     

Dual-head pinhole bone scintigraphy

This article describes dual-head pinhole bone scintigraphy (DHPBS), which makes use of two opposing pinhole-collimated detectors to obtain one pair of magnified images of bone and joint at one time. The aims are to reduce scan time and solve the problem of the blind zone that is created in the background in single-head pinhole bone scintigraphy. METHODS: DHPBS was used for normal hip and knee joints and one case each of lumbar spondylosis, vertebral compression fracture and pyoankle. The gamma camera used was a digital dual-head SPECT camera (Sopha Camera DST; Sopha Medical Vision International, Buc Cedex, France) connected to an XT data processor and a printer. Each of two opposing detectors was collimated with either a 3- or 5-mm pinhole collimator. The scan was performed 2-3 hr postinjection of 12-25 mCi 99mTc-oxidronate. Some 1500-2000 Kilocounts were accumulated at 15-40 min per pair. Anterior and posterior views were taken for the spine and hip and medial and lateral views for the knee and ankle. DHPBS images were correlated to radiographs. RESULTS: DHPBS produced a pair of high-resolution bone and joint images at one time, reducing scan time by nearly half for each image. The paired DHPBS images clearly visualized both foreground and background objects, which effectively eliminated the blind zone. CONCLUSION: DHPBS can significantly improve efficiency and diagnostic acumen.     

Two-dimensional array self-assembled quantum dot sub-diffraction waveguides with low loss and low crosstalk

We model and demonstrate the behavior of two-dimensional (2D) self-assembled quantum dot (QD) sub-diffraction waveguides. By pumping the gain-enabled semiconductor nanoparticles and introducing a signal light, energy coupling of stimulated photons from the QDs enables light transmission along the waveguide. Monte Carlo simulation with randomized inter-dot separation reveals that the optical gain necessary for unity transfer is 3.1 × 10(7)?m(-1) for a 2D (2?μm length by 500?nm width) array compared to 11.6 × 10(7)?m(-1) for a 1D (2?μm length) given 8?nm diameter quantum dots. The theoretical results are borne out in experiments on 2D arrays by measurement of negligible crosstalk component with as little as 200?nm waveguide separation and is indicative of near-field optical coupling behavior. The transmission loss for 500?nm wide structures is determined to be close to 3?dB/4?μm, whereas that for 100?nm width is 3?dB/2.3?μm. Accordingly, higher pump power and gain would be necessary on the narrower device to create similar throughput. Considering existing nanoscale propagation methods, which commonly use negative dielectric materials, our waveguide shows an improved loss characteristic with comparable or smaller dimensions. Thus, the application of QDs to nanophotonic waveguiding represents a promising path towards ultra-high density photonic integrated circuits.     

Electrical detection of fast reaction kinetics in nanochannels with an induced flow

Nanofluidic channels can be used to enhance surface binding reactions, since the target molecules are closely confined to the surfaces that are coated with specific binding partners. Moreover, diffusion-limited binding can be significantly enhanced if the molecules are steered into the nanochannels via either pressure-driven or electrokinetic flow. By monitoring the nanochannel impedance, which is sensitive to surface binding, low analyte concentrations have been detected electrically in nanofluidic channels within response times of 1-2 h. This represents a approximately 54 fold reduction in the response time using convective flow compared to diffusion-limited binding. At high-flow velocities, the presented method of reaction kinetics enhancement is potentially limited by force-induced dissociations of the receptor-ligand bonds. Optimization of this scheme could be useful for label-free, electrical detection of biomolecule binding reactions within nanochannels on a chip.     

Discrete‐time adaptive fuzzy control with hysteresis observer for a three‐axis flexure stage

Abstract

This paper first derives the discrete‐time dynamic model, including hysteresis effect, for a three‐axis piezoactuated micro/nano flexure stage. Based on the discrete‐time model, an adaptive controller with hysteresis variables observer is designed via Lyapunov stability theory. In the stable adaptive controller, a fuzzy function approximator with normalized gradient parameters update law is included to compensate for the identification inaccuracy, model uncertainty, and flexure coupling effects. Simulation results are used for illustrating control performance.