Immunohistochemistry in Irradiated Skin Tissue

Currently there is no effective treatment for radiation dermatitis that results from clinical or accidental radiation exposures. Radiation exposure can cause severe burns and sloughing of the skin and damage muscle and bone layers underneath the skin. Radiation exposure in cells results in several types of cell death, such as necrosis, apoptosis, or autophagy, or accelerated senescence. Preliminary experiments demonstrated that accelerated senescence is a primary response to radiation in normal skin cells in culture and skin tissue in vivo in mice. We wanted to use immunohistochemistry to identify the skin cells that undergo senescence in tissues obtained from 4 mice over a time course from 1-30 days following exposure to 17.9 Gy (0.6 Gy/min) irradiation. The different stains that are going to be used are hematoxylin and eosin stain which shows the morphology of the whole tissue, K15 which marks adult skin epidermal stem cells, p21/waf1 which is a marker for senescence, DCT which marks melanocyte stem cells, and c-kit which marks melanocytes and basal epithelial cells. The results from these experiments will help us to determine which cells to protect in order to treat severe radiation exposure

Familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after the appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas), congenital hypertrophy of the retinal pigment epithelium (CHRPE), desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system). A less aggressive variant of FAP, attenuated FAP (AFAP), is characterized by fewer colorectal adenomatous polyps (usually 10 to 100), later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back) are indicative of the Gardner variant of FAP. Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC) gene. Most patients (~70%) have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP), which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. Diagnosis is based on a suggestive family history, clinical findings, and large bowel endoscopy or full colonoscopy. Whenever possible, the clinical diagnosis should be confirmed by genetic testing. When the APC mutation in the family has been identified, genetic testing of all first-degree relatives should be performed. Presymptomatic and prenatal (amniocentesis and chorionic villous sampling), and even preimplantation genetic testing is possible. Referral to a geneticist or genetic counselor is mandatory. Differential diagnoses include other disorders causing multiple polyps (such as Peutz-Jeghers syndrome, familial juvenile polyps or hyperplastic polyposis, hereditary mixed polyposis syndromes, and Lynch syndrome). Cancer prevention and maintaining a good quality of life are the main goals of management and regular and systematic follow-up and supportive care should be offered to all patients. By the late teens or early twenties, colorectal cancer prophylactic surgery is advocated. The recommended alternatives are total proctocolectomy and ileoanal pouch or ileorectal anastomosis for AFAP. Duodenal cancer and desmoids are the two main causes of mortality after total colectomy, they need to be identified early and treated. Upper endoscopy is necessary for surveillance to reduce the risk of ampullary and duodenal cancer. Patients with progressive tumors and unresectable disease may respond or stabilize with a combination of cytotoxic chemotherapy and surgery (when possible to perform). Adjunctive therapy with celecoxib has been approved by the US Food and Drug Administration and the European Medicines Agency in patients with FAP. Individuals with FAP carry a 100% risk of CRC; however, this risk is reduced significantly when patients enter a screening-treatment program

Bone Marrow Protein Oxidation in Response to Ionizing Radiation in C57BL/6J Mice

The bone marrow is one of the most radio-sensitive tissues. Accidental ionizing radiation exposure can damage mature blood cells and hematopoietic progenitor/stem cells, and mortality can result from hematopoietic insufficiency and infection. Ionizing radiation induces alterations in gene and protein expression in hematopoietic tissue. Here we investigated radiation effects on protein carbonylation, a primary marker for protein oxidative damage. C57BL/6 mice were either sham irradiated or exposed to 7.5 Gy 60Co (0.6 Gy/min) total body irradiation. Bone marrow was obtained 24 h post-irradiation. Two dimensional (2-D) gel electrophoresis and Oxyblot immunodetection were used to discover carbonylated proteins, and peptide mass fingerprinting was performed for identification. 2D gels allowed the detection of 13 carbonylated proteins in the bone marrow; seven of these were identified, with two pairs of the same protein. Baseline levels of carbonylation were found in 78 kDa glucose-related protein, heat shock protein cognate 71 KDa, actin, chitinase-like protein 3 (CHI3L1), and carbonic anhydrase 2 (CAII). Radiation increased carbonylation in four proteins, including CHI3L1 and CAII, and induced carbonylation of one additional protein (not identified). Our findings indicate that the profile of specific protein carbonylation in bone marrow is substantially altered by ionizing radiation. Accordingly, protein oxidation may be a mechanism for reduced cell viability

Two-year follow-up of a randomized effectiveness trial evaluating MST for juveniles who sexually offend.

OBJECTIVE: Building on prior efficacy trials (i.e., university based, graduate students as therapists), the primary purpose of this study was to determine whether favorable 12-month outcomes obtained in a randomized effectiveness trial (i.e., implemented by practitioners in a community mental health center) of multisystemic therapy (MST) with juveniles who had sexually offended (JSO) were sustained through a second year of follow-up. METHOD: JSO (n = 124 male youth) and their families were randomly assigned to MST, which was family based and delivered by community-based practitioners, or to treatment as usual (TAU), which was primarily group-based cognitive-behavioral interventions delivered by professionals within the juvenile justice system. Youth averaged 14.7 (SD = 1.7) years of age at referral, were primarily African American (54%), and 30% were Hispanic. All youth had been diverted or adjudicated for a sexual offense. Analyses examined whether MST effects reported previously at 1-year follow-up for problem sexual behaviors, delinquency, substance use, and out-of-home placement were sustained through a second year of follow-up. In addition, arrest records were examined from baseline through 2-year follow-up. RESULTS: During the second year of follow-up, MST treatment effects were sustained for three of four measures of youth problem sexual behavior, self-reported delinquency, and out-of-home placements. The base rate for sexual offense rearrests was too low to conduct statistical analyses, and a between-groups difference did not emerge for other criminal arrests. CONCLUSIONS: For the most part, the 2-year follow-up findings from this effectiveness study are consistent with favorable MST long-term results with JSO in efficacy research. In contrast with many MST trials, however, decreases in rearrests were not observed

Protein Oxidation in the Lungs of C57BL/6J Mice Following X-Irradiation

Damage to normal lung tissue is a limiting factor when ionizing radiation is used in clinical applications. In addition, radiation pneumonitis and fibrosis are a major cause of mortality following accidental radiation exposure in humans. Although clinical symptoms may not develop for months after radiation exposure, immediate events induced by radiation are believed to generate molecular and cellular cascades that proceed during a clinical latent period. Oxidative damage to DNA is considered a primary cause of radiation injury to cells. DNA can be repaired by highly efficient mechanisms while repair of oxidized proteins is limited. Oxidized proteins are often destined for degradation. We examined protein oxidation following 17 Gy (0.6 Gy/min) thoracic X-irradiation in C57BL/6J mice. Seventeen Gy thoracic irradiation resulted in 100% mortality of mice within 127–189 days postirradiation. Necropsy findings indicated that pneumonitis and pulmonary fibrosis were the leading cause of mortality. We investigated the oxidation of lung proteins at 24 h postirradiation following 17 Gy thoracic irradiation using 2-D gel electrophoresis and OxyBlot for the detection of protein carbonylation. Seven carbonylated proteins were identified using mass spectrometry: serum albumin, selenium binding protein-1, alpha antitrypsin, cytoplasmic actin-1, carbonic anhydrase-2, peroxiredoxin-6, and apolipoprotein A1. The carbonylation status of carbonic anhydrase-2, selenium binding protein, and peroxiredoxin-6 was higher in control lung tissue. Apolipoprotein A1 and serum albumin carbonylation were increased following X-irradiation, as confirmed by OxyBlot immunoprecipitation and Western blotting. Our findings indicate that the profile of specific protein oxidation in the lung is altered following radiation exposure

An Informational Theory of Midterm Elections: The Impact of Iraq War Deaths on the

Reves, and several more I am sure I am forgetting for their constant reality checks when I started to lose sight of my goals. If I have left anyone out who feels they were slighted, I offer my humblest apologies for the omission. Finally I must thank the many different locations throughout Denton where this paper was written, including the UNT library, Banter and Jupiter House coffee shops, the bench in front of the public admin department in Wooten Hall, now sadly gone, all provided the workspace I needed to complete this paper, and I must give them my thanks. iii 1962 1966 1970 1974 1978 1982 1986 1990 1994 1998 for the highest offices on the ballot. In doing so I hope to illustrate the scholastic background I will be drawing upon for this paper. I also include some research on vote