Iowa Developments, January 2008, Volume 12, Number 1

Business news from the Iowa Department of Economic Development

Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study.

OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients were included who had genotypic resistance tests performed on plasma samples collected while antiretroviral therapy naive. TDR was defined as at least one resistance mutation from a list proposed for genotypic TDR surveillance. Multivariable logistic regression was used to analyze factors associated with detection of TDR, with virological (viral load<500 copies/mL) and CD4 count response (>or=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological suppression (those resistant to at least one drug prescribed versus susceptible), adjusted odds ratio: 0.68 (95% confidence interval: 0.27 to 1.71; P=0.408) or CD4 count response, adjusted odds ratio: 1.65 (95% confidence interval: 0.73 to 3.73; P=0.231). CONCLUSIONS: Prevalence of TDR in antiretroviral-naive patients was found to be in line with other European studies. No significant differences were found in virological and CD4 count response after initiation of first-line combination antiretroviral therapy between resistant and susceptible patients, possibly due to the small number of patients with resistance and consequently low power.

Space Utilization and Building Study for the Department of General Services, October 9, 2000

Purposes of this Report: • Recommend the most logical and economical options to address state governmental space needs in the Polk County metropolitan area to the year 2010. • Include building size, location, phasing, financing, method of project delivery and estimated cost. • Develop a software tool to compare costs of leasing vs. ownership of space. Methodology: Identify: 1. Current amount and location of owned and leased space, by agency; 2. Types of space and whether best located on or off of the Capitol Complex; 3. Utilization of space, noting over-crowding and under-utilization; 4. Current number of workstations for full and part time employees, Personnel Employment Organization (PEO) workers, contractors, interns, etc.; and, 5. History of staff levels to assist in the prediction of staff growth. Scope: This report focuses on 10 state-owned buildings located on the Capitol Complex and 48 leased spaces in the Polk County metropolitan area. (See Figures 1 and 2.) • Due to a separate space study under way by the Legislature, implications of area and staff for the State Capitol building are included only for the Governor, Lieutenant Governor, Treasurer, Secretary of State, Auditor and the Department of Management. • Because it is largely a museum building that does not have office space available for other agencies, the area and staff of the Historical Building are not fully addressed. • Only the parking implications of the new Judicial Building are included in this study because the building space is under the jurisdiction of the Judicial Branch and not available for other agencies. Several state-owned buildings are not included in the scope of this report, generally because they have highly focused purposes, and their space is not available for assignment to other agencies. Several leased locations are not included for similar reasons, including leases that do not fall within the authority of the Department of General Services.

IOWATER, Vol. 1, no.2, Summer 2000

Water fact sheet for Iowa Department of Natural Resources and the Geological Bureau.

Differential transgene expression profiles in rat brain, using rAAV2/1 vectors with tetracycline-inducible and cytomegalovirus promoters.

The biodistribution of transgene expression in the CNS after localized stereotaxic vector delivery is an important issue for the safety of gene therapy for neurological diseases. The cellular specificity of transgene expression from rAAV2/1 vectors (recombinant adeno-associated viral vectors pseudotyped with viral capsids from serotype 1) using the tetracycline-inducible (TetON) expression cassette in comparison with the cytomegalovirus (CMV) promoter was investigated in the rat nigrostriatal pathway. After intrastriatal injection, although green fluorescent protein (GFP) was expressed mainly in neurons with both vectors, the relative proportions of DARPP-32-positive projection neurons and parvalbumin-positive interneurons were, respectively, 13:1 and 2:1 for the CMV and TetON vectors. DARP32-positive neurons projecting to the globus pallidus were strongly GFP positive with both vectors, whereas those projecting to the substantia nigra pars reticulata (SNpr) were efficiently labeled by the CMV vector but poorly by the TetON vector. Numerous GFP-positive cells were evidenced in the subventricular zone with both vectors. However, in the olfactory bulb (OB), GFP-positive neurons were observed with the CMV vector but not the TetON vector. We conclude that the absence of significant amounts of transgene product in distant regions (SN and OB) constitutes a safety advantage of the AAV2/1-TetON vector for striatal gene therapy. Midbrain injections resulted in selective GFP expression in tyrosine hydroxylase-positive neurons by the TetON vector whereas with the CMV vector, GFP-positive cells covered a widespread area of the midbrain. The biodistribution of GFP protein corresponded to that of the transcripts and not of the viral genomes. We conclude that the rAAV2/1-TetON vector constitutes an interesting tool for specific transgene expression in midbrain dopaminergic neurons.

Iowa Board of Dental Examiners, August 5, 2003, Vol 1, no. 2

Newsletter produced by the Iowa Dental Board.

State of Iowa Space Utilization and Building Study, October 9, 2000

Executive Summary Purposes of this Report: • Recommend the most logical and economical options to address state governmental space needs in the Polk County metropolitan area to the year 2010. • Include building size, location, phasing, financing, method of project delivery and estimated cost. • Develop a software tool to compare costs of leasing vs. ownership of space. Methodology: Identify: 1. Current amount and location of owned and leased space, by agency; 2. Types of space and whether best located on or off of the Capitol Complex; 3. Utilization of space, noting over-crowding and under-utilization; 4. Current number of workstations for full and part time employees, Personnel Employment Organization (PEO) workers, contractors, interns, etc.; and, 5. History of staff levels to assist in the prediction of staff growth. Scope: This report focuses on 10 state-owned buildings located on the Capitol Complex and 48 leased spaces in the Polk County metropolitan area. (See Figures 1 and 2.) • Due to a separate space study under way by the Legislature, implications of area and staff for the State Capitol building are included only for the Governor, Lieutenant Governor, Treasurer, Secretary of State, Auditor and the Department of Management. • Because it is largely a museum building that does not have office space available for other agencies, the area and staff of the Historical Building are not fully addressed. • Only the parking implications of the new Judicial Building are included in this study because the building space is under the jurisdiction of the Judicial Branch and not available for other agencies. Several state-owned buildings are not included in the scope of this report, generally because they have highly focused purposes, and their space is not available for assignment to other agencies. Several leased locations are not included for similar reasons, including leases that do not fall within the authority of the Department of General Services.

Healthy Aging Update, February 1, 2006, Vol. 1, no. 2

This bimonthly electronic newsletter will provide information and resources on nutrition and health promotion and disease prevention. The Healthy Aging Update is produced for informal and educational purposes only. The newsletter will be distributed electronically and posted on the Department’s website at www.state.ia.us/elderaffairs.

Johne’s Disease–Beef, Fall 2009, Vol. 1, no. 2

Newsletter about controlling animal diseases, tips and techniques on how prevention works and the transportation of livestock.

p53-induced protein with a death domain (PIDD) isoforms differentially activate nuclear factor-kappaB and caspase-2 in response to genotoxic stress

Cells respond to DNA damage in a complex way and the fate of damaged cells depends on the balance between pro- and antiapoptotic signals. This is of crucial importance in cancer as genotoxic stress is implied both in oncogenesis and in classical tumor therapies. p53-induced protein with a death domain (PIDD), initially described as a p53-inducible gene, is one of the molecular switches able to activate a survival or apoptotic program. Two isoforms of PIDD, PIDD (isoform 1) and LRDD (isoform 2), have already been reported and we describe here a third isoform. These three isoforms are differentially expressed in tissues and cell lines. Genotoxic stress only affects PIDD isoform 3 mRNA levels, whereas isoforms 1 and 2 mRNA levels remain unchanged. All isoforms are capable of activating nuclear factor-kappaB in response to genotoxic stress, but only isoform 1 interacts with RIP-associated ICH-1/CED-3 homologous protein with a death domain and activates caspase-2. Isoform 2 counteracts the pro-apoptotic function of isoform 1, whereas isoform 3 enhances it. Thus, the differential splicing of PIDD mRNA leads to the formation of at least three proteins with antagonizing/agonizing functions, thereby regulating cell fate in response to DNA damage

Fonction ventriculaire gauche après revascularisation pour occlusion d'une coronaire d'une durée de 1-2 heures [Left ventricular function following revascularization for occlusion of a coronary artery lasting 1 to 2 hours].

The time-lag between coronary occlusion and irreversible damage to the myocardium is ill-defined in man. In 10 patients the changes in left ventricular function have been studied after coronary occlusion during diagnostic or therapeutic cardiac catheterization of 1-2 hours' duration. Revascularization was achieved either surgically or through intracoronary streptokinase infusion. The interval between occlusion and onset of extracorporal circulation or reopening was 61 to 119 minutes. Despite enzyme elevation (CPK, CK-MB, SGOT) and appearance of Q-waves in 5 patients, no significant alteration of left ventricular function was noted on repeat cardiac catheterization 10 to 230 days after the accident. These observations, suggest that coronary occlusion of 1-2 hours' duration fails to produce significant irreversible damage to the myocardium despite electrocardiographic and enzymatic signs of myocardial infarction.

The White Cane Magazine, Spring 2010, Vol. 1, no. 2

Quarterly newsletter produced by the Iowa Department of Blind, about the information and activities that are on going.

Immunization Update, June 2006, Vol. 1, no.2

Monthly newsletter for the Iowa Department of Public Health

TRAMP, a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas(Apo-1/CD95).

A novel member of the tumor necrosis factor (TNF) receptor family, designated TRAMP, has been identified. The structural organization of the 393 amino acid long human TRAMP is most homologous to TNF receptor 1. TRAMP is abundantly expressed on thymocytes and lymphocytes. Its extracellular domain is composed of four cysteine-rich domains, and the cytoplasmic region contains a death domain known to signal apoptosis. Overexpression of TRAMP leads to two major responses, NF-kappaB activation and apoptosis. TRAMP-induced cell death is inhibited by an inhibitor of ICE-like proteases, but not by Bcl-2. In addition, TRAMP does not appear to interact with any of the known apoptosis-inducing ligands of the TNF family.

Feasibility of radiotherapy or chemoradiotherapy after taxane-based induction chemotherapy for nonoperated locally advanced head and neck squamous cell carcinomas.

To assess the use of radiotherapy (RT) or concurrent chemoradiotherapy (CRT) following taxane-based induction chemotherapy (T-ICT) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) and to evaluate the tolerability of CRT after T-ICT. From 01/2006 to 08/2012, 173 LAHNSCC patients treated as a curative intent by T-ICT, followed by definitive RT/CRT were included in this analysis. There was an 86% objective response (OR) after ICT among 154 evaluable patients. Forty-four patients received less than three cycles (25%) and 20 received only one cycle of T-ICT. The 3-year actuarial overall survival (OS) was 49% and there was no OS difference according to the type of ICT (regimen or number of cycle) or the addition of concurrent CT (cisplatin, carboplatin, or cetuximab) to RT. In multivariate analysis (MVA), clinically involved lymph node (cN+), age more than 60 years, the absence of OR after ICT, and performance status of at least 1 predicted for a decreased OS, with hazard ratios (HR) of 2.8, 2.2, 2.1, and 2, respectively. The 3-year actuarial locoregional control (LRC) and distant control (DC) rates were 52 and 73%, respectively. In MVA, the absence of OR after ICT (HR: 3.2), cN+ (HR: 3), and age more than 60 years (HR: 1.7) were prognostic for a lower LRC whereas cN+ (HR: 4.2) and carboplatin-based T-ICT (HR: 2.9) were prognostic for a lower DC. The number of cycles (≤ 2) received during ICT was borderline significant for DC in the MVA (P=0.08). Among patients receiving less than or equal to three cycles of ICT, higher outcomes were observed in patients who received cisplatin-based T-ICT (vs. carboplatin-based T-ICT) or subsequent CRT (vs. RT). T-ICT in our experience, followed by RT or CRT, raises several questions on the role and type of induction, and the efficacy of CRT over RT. The role of RT or CRT following induction, although feasible in these advanced patients, awaits answers from randomized trials.