Short double-stranded RNA induces transcriptional gene silencing in human cancer cells in the absence of DNA methylation.

Double-stranded RNA molecules targeted to gene promoter regions can induce transcriptional gene silencing in a DNA cytosine methylation-dependent manner in plants (RNA-dependent DNA methylation). Whether a similar mechanism exists in mammalian systems is a vital and controversial issue. DNA methylation is an important component in mammalian gene silencing for normal processes such as gene imprinting and X-chromosome inactivation, and aberrant CpG island hypermethylation at tumor-suppressor promoters is associated with transcriptional silencing and loss of gene function in cancer.

Characterization of the third-harmonic radiation generated by intense laser self-formed filaments propagating in air.

We perform laboratory experiments to study ultraviolet radiation generated by intense self-formed laser filaments produced by propagating high-power femtosecond laser pulses in air. The laser used in the experiment is a 0.5 TW Ti:sapphire system with the center wavelength at 800 nm.

Large-scale screens for cDNAs with in vivo activity.

The pace of biological investigation has been greatly accelerated by technologies that permit comprehensive inventory of gene expression under diverse conditions. We have been developing and using approaches to understand gene function that are based on functional assessments of gene activity, using automated expression cloning followed by gene knockdown using shRNA or by gene knockout. Some recent developments in expression screens and methods to expedite the formation of targeted mutations in mice are discussed.

Comparison of stereoscopic digital imaging and slide film photography in the identification of macular degeneration.

Background: This study compared the sensitivity and specificity of stereoscopic digital photography of the retina through a dilated pupil with a 45 degrees nonmydriatic camera and Joint Photographic Experts Group (JPEG) compression of the images with the sensitivity and specificity of 35-mm slide film photography in the identification of age-related macular degeneration (AMD).

Methods: Consecutive patients with a diagnosis of AMD were enrolled. Stereoscopic retinal images of the disc, macula and temporal macula were captured with a digital 45 degrees nonmydriatic camera (then compressed into JPEG format) and with a standard fundus camera and slide film.

Inhibition of MAPK and NF-kappa B pathways is necessary for rapid apoptosis in macrophages infected with Yersinia.

Macrophages respond to infection with pathogenic Yersinia species by activating MAPK- and NF-kappaB-signaling pathways. To counteract this response, Yersiniae secrete a protease (Yersinia outer protein J (YopJ)) that is delivered into macrophages, deactivates MAPK- and NF-kappaB-signaling pathways, and induces apoptosis. NF-kappaB promotes cell survival by up-regulating expression of several apoptosis inhibitor genes.

Targeting quantum dots to surface proteins in living cells with biotin ligase.

Escherichia coli biotin ligase site-specifically biotinylates a lysine side chain within a 15-amino acid acceptor peptide (AP) sequence. We show that mammalian cell surface proteins tagged with AP can be biotinylated by biotin ligase added to the medium, while endogenous proteins remain unmodified. The biotin group then serves as a handle for targeting streptavidin-conjugated quantum dots (QDs).

Discovery of S-phase arresting agents derived from noscapine.

Analogues of the natural product noscapine were synthesized, and their potential as antitumor agents were examined. The discovery of a novel regio- and stereoselective O-demethylation led to the synthesis of several O-alkylated analogues that induced an unexpected S-phase arrest of mammalian cells. Compound 4a was the most potent analogue inhibiting cell proliferation at an EC(50) of 1.

Direct characterization of self-guided femtosecond laser filaments in air.

High-power femtosecond laser pulses propagating in air form self-guided filaments that can persist for many meters. Characterizing these filaments has always been challenging owing to their high intensity. An apparently novel diagnostic is used to directly measure the fluence distribution of femtosecond laser pulses after they have formed self-guided optical filaments in air.

Quasimonoenergetic electrons from unphased injection into channel guided laser wakefield accelerators.

A high-quality electron beam can be extracted from a channel guided laser wakefield accelerator without confining the injected particles to a small region of phase. By careful choice of the injection energy, a regime can be found where uniformly phased particles are quickly bunched by the accelerator itself and subsequently accelerated to high energy. The process is particularly effective in a plasma channel because of a favorable phase shift that occurs in the focusing fields.

Site-specific labeling of cell surface proteins with biophysical probes using biotin ligase.

We report a highly specific, robust and rapid new method for labeling cell surface proteins with biophysical probes. The method uses the Escherichia coli enzyme biotin ligase (BirA), which sequence-specifically ligates biotin to a 15-amino-acid acceptor peptide (AP). We report that BirA also accepts a ketone isostere of biotin as a cofactor, ligating this probe to the AP with similar kinetics and retaining the high substrate specificity of the native reaction.

Site-specific labeling of proteins with small molecules in live cells.

The principal bottleneck for the utilization of small-molecule probes in live cells is the shortage of methodologies for targeting them with very high specificity to biological molecules or compartments of interest. Recently developed methods for labeling proteins with small-molecule probes in cells employ special protein or peptide handles that recruit small-molecule ligands, harness enzymes to catalyze small-molecule conjugation or hijack the cell's protein translation machinery.

Surgical treatment of infected aneurysms and pseudoaneurysms of the thoracic and abdominal aorta.

Background: To review the outcome of infected aneurysms and pseudoaneurysms of the thoracic and abdominal aorta treated in a major teaching hospital.

Methods: Between December 1994 and January 2003, 13 infected aortic aneurysms and pseudoaneurysms (5 thoracic, 4 paravisceral, 4 infrarenal) in 10 consecutive patients were treated surgically. Aortic debridement with in situ reconstruction is our standard practice.

Detection of C. pneumoniae by polymerase chain reaction-enzyme immunoassay in abdominal aortic aneurysm walls and its association with rupture.

Objective: Serological studies have suggested that one of the risk factors for aneurysm development is C. pneumoniae infection. The purpose of this study was to evaluate whether there is an association between the presence of C.

Combined endovascular stent grafting and endoscopic injection of fibrin sealant for aortoenteric fistula complicating esophagectomy.

A 67-year-old man with previous total gastrectomy and roux-en-Y esophagojejunostomy had hematemesis 4 weeks after esophagectomy performed because of carcinoma of the esophagus. Investigation showed an aortojejunal fistula with a thoracic aortic pseudoaneurysm. Endovascular stent grafting of the pseudoaneurysm, followed by endoscopic injection of fibrin sealant for the fistula, was performed, and the infection was controlled with broad-spectrum antibiotic agents together with drainage and daily irrigation of the pseudoaneurysm sac.

Aortic aneurysm morphology in Asians: features affecting stent-graft application and design.

Purpose: To determine the morphological features of abdominal aortic aneurysms (AAA) in an Asian cohort in order to identify unique features relevant to stent-graft planning and application.

Methods: Spiral computed tomography (CT) and angiographic assessment of AAA morphology was performed on 65 ethnic Chinese (58 men; mean age 74 years, range 50-87) who underwent endovascular AAA repair. Morphological parameters were compared with published data from American and European patients.

The gubernaculum in testicular descent and cryptorchidism.

The gubernaculum plays an essential role in the complex mechanism of testicular descent and inguinal hernia closure. Understanding this complex developmental process is gradually allowing us insight into how to regulate normal descent and also treat maldescended testes.

Dementia following posterior cortical atrophy--a descriptive clinical case report.

Whether posterior cortical atrophy is a distinct entity or a variant of one of the other degenerative processes continues to be debated. We describe five patients four of whom had bilateral changes of posterior cortical atrophy on the CT scan. These four had a cluster of symptoms consistent with parieto-occiptial dysfunction together with a spectrum of dementia.

Blood loss and transfusion in elective abdominal aortic aneurysm surgery.

Background: Intraoperative blood loss and transfusion are known determinants of mortality and morbidity of elective abdominal aortic aneurysm (AAA) repair. The present study analysed the pattern of blood loss and transfusion and evaluated the risk factors of blood loss during open repair of infrarenal AAA.

Methods: Blood loss, transfusion and fluid replacement during elective open repair operation for patients with infrarenal AAA were correlated to demographic data, operative findings and procedural information.

Mammalian DNA methyltransferase 1: inspiration for new directions.

The role of DNA methyltransferase 1, DNMT1, in human cancer cells has recently been contested. In this setting, DNMT1's function as the sole maintenance methyltransferase was based on the assumption that its biological activity is identical to the mouse homologue. However, the application of recent technological advances, including gene targeting and siRNA mediated ablation studies, has cast doubt on this presumed role.

Laparoscopic transperitoneal clipping of the inferior mesenteric artery for the management of type II endoleak after endovascular repair of an aneurysm.

We report the case of a high risk patient with an abdominal infrarenal aortic aneurysm (AAA) who was treated by endovascular technique and the subsequent management of a type II endoleak by the laparoscopic approach. In this case, a 74-year-old woman with a 6-cm infrarenal AAA underwent endovascular repair using a bifurcated stent-graft device. Surveillance CT scan showed a persistent type II endoleak at 1 week and 3 months after the operation.

A randomised controlled trial of morphine versus phenobarbitone for neonatal abstinence syndrome.

Background: The incidence of neonatal abstinence syndrome (NAS) has increased 10-fold over the last decade in Glasgow. In the Princess Royal Maternity Hospital, it now accounts for 17% of special care baby unit (SCBU) admissions.

Objective: To compare opiate replacement therapy (morphine sulphate) with the present standard treatment (phenobarbitone) for management of NAS.

Endovascular repair for multiple Salmonella mycotic aneurysms of the thoracic aorta presenting with Cardiovocal syndrome.

Salmonella mycotic thoracic aortic aneurysm is a rare but life-threatening condition. We report a 59-year-old man with two Salmonella mycotic thoracic aortic aneurysms, presented with fever and chills associated with hoarseness due to left vocal cord palsy (Cardiovocal syndrome). Successful endovascular repair was performed using two Talent thoracic stent-graft devices deployed separately to cover the two mycotic aneurysms.

Estrogen regulates vaginal sensory and autonomic nerve density in the rat.

Vaginal function is strongly influenced by reproductive hormone status. Vaginal dysfunction during menopause is generally assumed to occur because of diminished estrogen-mediated trophic support of vaginal target cells. However, peripheral neurons possess estrogen receptors and are potentially responsive to gonadal steroid hormones.

[Study on a new IL-12 inducing gene NAP2].

Aim: To study the function of newly cloned NF-kappaB-activating gene (NAP2) and its mechanism. METHEDS: Activation of NF-kappaB and IL-12 promoters as well as modulation of IL-12 synthesis by NAP2 in macrophages were observed by NF-kappaB and IL-12 luciferase reporter assay and intracellular IL-12 staining.

Results: NAP2 could activate NF-kappaB and IL-12 promoter.