Structure and activity of CPNGRC: a modified CD13/APN peptidic homing motif.

Asn-Gly-Arg peptides have been designed as vehicles for the delivery of chemotherapeutics, magnetic resonance imaging contrast agents, and fluorescence labels to tumor cells, and cardiac angiogenic tissue. Specificity is derived via an interaction with aminopeptidase N, also known as CD13, a cell surface receptor that is highly expressed in angiogenic tissue. Peptides containing the CNGRC homing sequence tethered to a pro-apoptotic peptide sequence have the ability to specifically induce apoptosis in tumor cells.

Genetic epidemiology of COPD (COPDGene) study design.

Background: COPDGene is a multicenter observational study designed to identify genetic factors associated with COPD. It will also characterize chest CT phenotypes in COPD subjects, including assessment of emphysema, gas trapping, and airway wall thickening. Finally, subtypes of COPD based on these phenotypes will be used in a comprehensive genome-wide study to identify COPD susceptibility genes.

Variants in FAM13A are associated with chronic obstructive pulmonary disease.

We performed a genome-wide association study for chronic obstructive pulmonary disease (COPD) in three population cohorts, including 2,940 cases and 1,380 controls who were current or former smokers with normal lung function. We identified a new susceptibility locus at 4q22.1 in FAM13A and replicated this association in one case-control group (n = 1,006) and two family-based cohorts (n = 3,808) (rs7671167, combined P = 1.

Phase II study of pemetrexed in patients with advanced neuroendocrine tumors.

Purpose: In some reports, 5-fluorouracil has been associated with modest activity in patients with neuroendocrine tumors. Pemetrexed is a multitargeted antifolate with activity in tumor types not significantly responsive to other antifolates. We evaluated the efficacy of pemetrexed in a phase II study of patients with advanced neuroendocrine tumors.

Differential patterning of neuronal, glial and neural progenitor cells on phosphorus-doped and UV irradiated diamond-like carbon.

Diamond-like carbon (DLC) is an attractive biomaterial for coating human implantable devices. Our particular research interest is in developing DLC as a coating material for implants and electrical devices for the nervous system. We previously reported that DLC is not toxic to N2a neuroblastoma cells or primary cortical neurons and showed that phosphorus-doped DLC (P:DLC) could be used to produce patterned neuron networks.

Differential roles for ETS, CREB, and EGR binding sites in mediating VEGF receptor 1 expression in vivo.

Vascular endothelial growth factor receptor 1 (VEGFR1) is a marker for endothelial-specific gene expression. We previously reported that the human VEGFR1 promoter (between -748 and +284) contains information for expression in the intact endothelium of transgenic mice. The objective of this study was to dissect the cis-regulatory elements underlying VEGFR1 promoter activity in vitro and in vivo.

Extracellular superoxide dismutase and risk of COPD.

Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide. COPD is strongly related to cigarette smoke exposure, but not all smokers develop the disease. It is thought that COPD progresses slowly over time stimulated by environmental exposures, including free radicals from cigarette smoke, which ultimately establish chronic inflammation and result in a progressive destruction of lung tissues.

Patterned growth of neuronal cells on modified diamond-like carbon substrates.

Diamond-like carbon (DLC) has been explored as a biomaterial with potential use for coating implantable devices and surgical instruments. In this study the interaction of DLC with mammalian neuronal cells has been studied along with its modifications to improve its function as a biomaterial. We describe the use of DLC, oxidised DLC and phosphorus-doped DLC to support the growth and survival of primary central nervous system neurones and neuroblastoma cells.

Joint fluid antioxidants are decreased in osteoarthritic joints compared to joints with macroscopically intact cartilage and subacute injury.

Objective: Excess reactive oxygen species and oxidative damage have been associated with the pathogenesis of osteoarthritis (OA). Extracellular superoxide dismutase (EC-SOD or SOD3) scavenges superoxide is the major catalytic antioxidant in joint fluid and is decreased in OA cartilage. We studied human joint fluid samples to test whether there is an association between OA and EC-SOD or other low molecular antioxidants in the joint fluid.

Phase I and pharmacokinetic study of S-1 administered for 14 days in a 21-day cycle in patients with advanced upper gastrointestinal cancer.

Purpose: S-1 is a novel oral fluoropyrimidine that combines tegafur with CDHP and oxonic acid. To decrease the incidence of late onset, severe diarrhea observed in a previous study, a phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1 utilizing a 14-day schedule, repeated every 21 days, in patients with chemotherapy-refractory upper gastrointestinal malignancies.

Methods: S-1 was administered orally, twice-daily, at an initial dose level of 30 mg/m2/dose; doses were escalated by 5 mg/m2 at each level.

Subcellular localization of tyrosine-nitrated proteins is dictated by reactive oxygen species generating enzymes and by proximity to nitric oxide synthase.

Using high-resolution immuno-electron microscopy the steady-state subcellular distribution of tyrosine-nitrated proteins in different cells and tissues was evaluated. In quiescent eosinophils and neutrophils in the bone marrow intracellular nitrated proteins were mainly restricted to the peroxidase-containing secretory granules. The inducible nitric oxide synthase (iNOS) was expressed in the same granules.

Tooth whitening: tooth color changes following treatment by peroxide and light.

Objective: This study examined the use of color measurement to determine tooth color in a study of bleaching with peroxide and light used separately and in combination. Two measurement protocols were evaluated for their ability to reveal differences between treatments and confirm tooth shade evaluations.

Methodology: Before and after treatment, 43 subjects were evaluated for tooth color using a shade guide and a chromameter.

Phase I and pharmacokinetic study of the dolastatin-15 analogue tasidotin (ILX651) administered intravenously on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors.

Purpose: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of tasidotin (ILX651), a dolastatin-15 analogue, when administered on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors.

Patients And Methods: Thirty-two patients were treated with 92 courses of tasidotin through seven dose levels determined by a modified Fibonacci scheme ranging from 3.9 to 45.

Extracellular superoxide dismutase and oxidant damage in osteoarthritis.

Objective: To use human cartilage samples and a mouse model of osteoarthritis (OA) to determine whether extracellular superoxide dismutase (EC-SOD) is a constituent of cartilage and to evaluate whether there is a relationship between EC-SOD deficiency and OA.

Methods: Samples of human cartilage were obtained from femoral heads at the time of joint replacement surgery for OA or femoral neck fracture. Samples of mouse tibial cartilage obtained from STR/ort mice and CBA control mice were compared at 5, 15, and 35 weeks of age.

Microbiological changes associated with dental prophylaxis.

Background: Despite the common application of dental prophylaxis as part of patient therapy, there is little reported that describes the microbiological impact of this treatment.

Methods: The authors gave 20 healthy college-aged subjects three dental prophylaxes with a fluoride-containing prophylaxis paste during a two-week period and instructed them in oral hygiene. They evaluated the microbiological composition of dental plaque samples collected before and after treatment using DNA probe analysis.

Orthopaedics in the Buddhist kingdom of Bhutan.

Volunteering as the only orthopaedic surgeon in the small Asian country of Bhutan provided a fascinating introduction to international work. The orthopaedic work predominantly was trauma and osteomyelitis. Treatment of most problems was complicated by patient delays in obtaining medical care, usually related to transportation difficulties in a steep mountainous land with few roads.

The efficacy of hyoscine hydrobromide in reducing side-effects induced during immersion in virtual reality.

Background: Regan and Price (1994) investigated the frequency of occurrence and severity of side-effects of using an immersion virtual reality system in 150 subjects: 61% of the subjects reported symptoms of malaise at some point during a 20-min immersion and 10-min post-immersion period. This paper describes a double-blind placebo-controlled study that investigated whether 300 microgram of hyoscine/scopolamine hydrobromide administered to subjects prior to immersion in virtual reality was effective in reducing side-effects experienced during immersion.

Hypothesis: It was hypothesized that the hyoscine hydrobromide would cause a significant reduction in reported symptoms.

The frequency of occurrence and severity of side-effects of immersion virtual reality.

Virtual reality (VR) has become increasingly well-known over the last few years. However, little is known about the side-effects of prolonged immersion in VR. This study set out to investigate the frequency of occurrence and severity of side-effects of using an immersion VR system.

Spinal arteriovenous malformation.

The authors discuss a patient with a large (15 x 10 x 12 cm), bony soft tissue intradural arteriovenous malformation (AVM) who presented with a 20-year history of back pain. Plain radiographs revealed a destructive lesion. Magnetic resonance imaging showed serpentine vascular structures within the thecal sac and lytic bone lesions with multiple level involvement.