Joseph Wood

Inhibition of estrogen stimulated mitogenesis by 3-phenylacetylamino-2,6-piperidinedione and its Para-hydroxy analog

3-Phenylactetylamino-2,6-piperidinedione (A10) inhibited estradiol stimulated cell growth in the MCF-7 (E3) human breast tumor cell line in vivo and in vitro. While high concentrations of A10 were needed to inhibit cell proliferation (IC50 = 3 x 10(-3) M in vitro), the compound demonstrated little toxicity. The effect appeared specific since a hydrolysis product of A10, phenylacetylglutamine, demonstrated no growth inhibitory activity at similar concentrations in MCF-7 (E3) cells in vitro. A computer designed analog, p-hydroxy A10, was more potent than A10 in inhibiting activity in MCF-7 (E3) cells in vitro. The IC50 for p-hydroxy A10 was 7 x 10(-6) M which was comparable to that of the antiestrogen, tamoxifen (IC50 1 x 10(-7) M). All three compounds caused a decline in estrogen receptor levels in a dose-dependent fashion. A10 also inhibited estradiol induction of progesterone receptors. Examination of protein kinase activity following an acute exposure to a 10(-11) M growth stimulatory dose of estradiol revealed a 168% increase in protein kinase activity over that of untreated control cells. A10 in a dose-responsive fashion inhibited the estradiol stimulated increase in protein kinase activity. The protein kinase activity was also inhibited by p-hydroxy A10. These activities of A10 and p-hydroxy A10 coupled with the low toxicity and novelty of the basic A10 structure provide an exciting possibility of developing a new class of clinically useful antineoplastic drugs with minimal side effects.

3-Phenylacetylamino-2,6-Piperidinedione Inhibition of Rat Nb2 Lymphoma Cell Mitogenesis

Abstract 3-Phenylacetylamino-2,6-piperidinedione (A10), an amino acid analog, has been reported to possess antineoplastic activity against certain neoplastic tissues. The antimitogenic properties of A10 were studied by determining its effect on prolactin (PRL)- and interleukin 2 (IL-2)-stimulated mitogenic responses in the rat Nb2 lymphoma cell line. The addition of A10 (1–12 mM) to PRL (0.4 ng/ml)-stimulated cells inhibited growth in a dose-dependent manner. DNA synthesis patterns studied by thymidine incorporation demonstrated that A10 was significantly inhibitory (25% at 20 hr; 50% at 40 hr, P < 0.01). IL-2 stimulation of mitogenesis was also sensitive to A10 inhibition. The inhibition of PRL stimulated mitogenesis was reversible when A10 was removed after 24 hr of culture and A10 showed no toxicity in a chromium release assay. These data suggest that A10 effects may be cytostatic, rather than cytotoxic.

Continuous remote vital sign/environment monitoring for returning soldier adjustment assessment

A three-stage study to develop and test an unobtrusive room sensor unit and subject data management system to discover correlation between sensor-based time-series measurements of sleep quality and clinical assessments of combat veterans suffering from Post-traumatic Stress Disorder (PTSD) and mild Traumatic Brain Injury (TBI), is described. Experiments and results for testing sensitivity and robustness of the sensor unit and data management protocol are provided. The current sensitivity of remote vital sign monitoring system is below 20% and 10% for respiration and heart rates, respectively.

An application of interdependence theory to military medical research teams: Cultural noise, tradeoffs, and meaning

ABSTRACT To better manage costs and effectiveness of a team or enterprise, the organizational sciences, social sciences and medical field are seeking new theory to transform teams and enterprises with computational models of complex social behavior that create “smart” systems. We have proposed to fulfill these calls with new theory, but ours is still under development. In a field application, we studied an electronic Institutional Review Board (eIRB) operating across a large complex of military medical scientists and researchers in Department of Defense (DoD) hospitals and clinics. As part of a field study of how the eIRB has transformed processes for DoD, we completed three comparable focus groups at a small and three focus groups at a large research site, one focus group of the eIRBs system managers, and one focus group of a competing eIRB operating in DoD (the latter group results are not reviewed at this time). We found tentative support for our theory: more noise (entropy) is being generated at the small site along with less research performed; cultural noise at both sites reflected an intransigence by sites to be transformed by adopting standardized forms; and the meaning of the findings differed between the small and large sites.

Sleep and activity monitoring for Returning Soldier Adjustment Assessment

This paper describes the development of unobtrusive room sensors to discover relationships between sleep quality and the clinical assessments of combat soldiers suffering from post-traumatic stress disorder (PTSD) and mild traumatic brain injury (TBI). We consider the use of a remote room sensor unit composed of a Doppler radar, light, sound and other room environment sensors. We also employ an actigraphy watch. We discuss sensor implementation, radar data analytics and preliminary results using real data from a Warrior Transition Battalion located in Fort Gordon, GA. Two radar analytical approaches are developed and compared against the actigraphy watch estimates - one, emphasizing system knowledge; and the other, clustering on several radar signal features. The radar analytic algorithms are able to estimate sleep periods, signal absence and restlessness in the bed. In our test cases, the radar estimates are shown to agree with the actigraphy watch. PTSD and mild-TBI soldiers do often show signs of sporadic and restless sleep. Ongoing research results are expected to provide further insight.

Autonomic Arousal during Group Decision Making Consensus Rules versus Majority Rules: Pilot Study

Organizational theory is in a poor state today. Supporting this claim, an article in Nature in 2011 listed the top challenges, including at fifth, the inability by social scientists to aggregate individual data to group, organizational and system levels. We have proposed that this failure derives from treating interdependence as a hindrance to experimental replications rather than the primary characteristic of social behavior. Recent studies have shown that bistability can be used theoretically to explain states of interdependence common to group debates preceding a decision (e.g., interdependently speaking and listening, and reacting). The goal of this study is to investigate interdependence in groups in the laboratory when specific parameters are placed on debate outcomes. Participants are instructed to engage in debate with one another over various topics (i.e., business, abortion, and race) and placed under one of two decision rules as instructed: consensus or majority rule. The degree to which participants remain “engaged” in the debate is of particular interest in this study. Prior to the test trial each participant completes a pre-discussion questionnaire designed to ascertain personal beliefs regarding each of the topics discussed. Participants complete a similar questionnaire immediately following the test trials. In addition, galvanic skin responses (GSR) and utterance counts over time are being obtained from randomly selected participants as a measure of autonomic arousal. We plan to analyze with time series. We expect that time-series data from groups, teams and organizations can augment self-reported data collected from individuals. Preliminary findings will be reviewed.

Military Medical Department Research Centers

We review our research with military Medical Department Research Centers (MDRC; a pseudonym).In 2006, we first proposed an electronic data system with metrics to better measure performance for the MDRCs. The data management system evolved into an electronic system for an Institutional Review Board (e-IRB) at one site. We foresaw that an e-IRB could provide the metrics to better monitor MDRC practices. Now that the eIRB is operational, metrics can measure how well the present mission of the MDRCs is being met across its system (improved patient care, increased scientific knowledge, and improved graduate student education); and, how well its vision is achieved (transforming the present mission of MDRCs to prepare for future missions).