LOW-DOSE GAMMA-RADIATION INHIBITS BENZO[A]PYRENE-INDUCED LUNG ADENOMA DEVELOPMENT IN A/J MICE

Low-dose ionizing radiation (LDR) may lead to suppression of smoking-related lung cancer. We examined the effects of a known cigarette smoke carcinogen Benzo[a]pyrene (B[a]P) alone or in combination with fractionated low-dose gamma radiation (60 – 600 mGy total dose) on the induction of lung neoplasms in the A/J mouse. Our results show that 600 mGy of gamma radiation delivered in six biweekly fractions of 100 mGy starting 1 month after B[a]P injection significantly inhibits the development of lung adenomas per animal induced by B[a]P. Our data also indicated that the six biweekly doses suppressed the occurrence of spontaneous hyperplastic foci in the lung, although this suppression failed to reach statistical significance when analyzed as average foci per lung possibly related to the small sample sizes used for the control and test groups

The challenge of measuring intra-individual change in fatigue during cancer treatment

Evaluate how well three different patient-reported outcomes (PROs) measure individual change

Brief Functional Analysis and Treatment of Tantrums associated with Transitions in Preschool Children

A brief functional analysis was used to examine the influence of termination of prechange activities and initiation of postchange activities on tantrums exhibited by 2 preschool children. For 1 participant, tantrums were maintained by access to certain (pretransition) activities. For a 2nd participant, tantrums were maintained by avoidance of certain task initiations. Although advance notice of an upcoming transition was ineffective, differential reinforcement of other behavior plus extinction reduced tantrums for both participants

Noncontingent Reinforcement as Treatment for Food Refusal and Associated Self-Injury

We examined the use of noncontingent reinforcement to decrease self-injury and increase bite acceptance in a child who exhibited food refusal. First, a brief functional analysis suggested that self-injury was maintained by escape from food presentation. Next, we evaluated an intervention that involved noncontingent access to a video during feeding sessions. Results of the intervention showed a decrease in self-injury and an increase in bite acceptance

Radiobiological studies using gamma and x rays.

There are approximately 500 self-shielded research irradiators used in various facilities throughout the U.S. These facilities use radioactive sources containing either 137Cs or 60Co for a variety of biological investigations. A report from the National Academy of Sciences[1] described the issues with security of particular radiation sources and the desire for their replacement. The participants in this effort prepared two peer-reviewed publications to document the results of radiobiological studies performed using photons from 320-kV x rays and 137Cs on cell cultures and mice. The effectiveness of X rays was shown to vary with cell type

Radiobiological studies using gamma and x rays.

There are approximately 500 self-shielded research irradiators used in various facilities throughout the U.S. These facilities use radioactive sources containing either 137Cs or 60Co for a variety of biological investigations. A report from the National Academy of Sciences[1] described the issues with security of particular radiation sources and the desire for their replacement. The participants in this effort prepared two peer-reviewed publications to document the results of radiobiological studies performed using photons from 320-kV x rays and 137Cs on cell cultures and mice. The effectiveness of X rays was shown to vary with cell type

Safety and biodistribution assessment of sc-rAAV2.5IL-1Ra administered via intra-articular injection in a mono-iodoacetate-induced osteoarthritis rat model

Interleukin-1 (IL-1) plays an important role in the pathophysiology of osteoarthritis (OA), and gene transfer of IL-1 receptor antagonist (IL-1Ra) holds promise for OA treatment. A preclinical safety and biodistribution study evaluated a self-complementary adeno-associated viral vector carrying rat IL-1Ra transgene (sc-rAAV2.5rIL-1Ra) at 5 × 108, 5 × 109, or 5 × 1010 vg/knee, or human IL-1Ra transgene (sc-rAAV2.5hIL-1Ra) at 5 × 1010 vg/knee, in Wistar rats with mono-iodoacetate (MIA)–induced OA at days 7, 26, 91, 180, and 364 following intra-articular injection. The MIA-induced OA lesions were consistent with the published data on this model. The vector genomes persisted in the injected knees for up to a year with only limited vector leakage to systemic circulation and uptake in tissues outside the knee. Low levels of IL-1Ra expression and mitigation of OA lesions were observed in the vector-injected knees, albeit inconsistently. Neutralizing antibodies against the vector capsid developed in a dose-dependent manner, but only the human vector induced a small splenic T-cell immune response to the vector capsid. No local or systemic toxicity attributable to vector administration was identified in the rats as indicated by clinical signs, body weight, feed consumption, clinical pathology, and gross and microscopic pathology through day 364. Taken together, the gene therapy vector demonstrated a favorable safety profile