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Evaluating sharp force trauma (SFT) injuries to bone inflicted by a larger class of chopping/hacking tools (i.e., swords, axes, hatchets, machetes, and cleavers) is a growing area within the field of forensics. Previous studies have demonstrated promise regarding tool differentiation through the utilization of microscopic cut mark characteristics. However, this is an area that warrants additional investigation as there has yet to be a comprehensive study that incorporates the majority of these microscopic chopping/hacking cut mark characteristics into one analysis. The purpose of the current research was to analyze a large sample of microscopic cut mark characteristics derived from the current chopping/hacking literature to determine if differentiation of tool type could be made based on the microscopic cut mark characteristics. An additional goal of the current research is to develop standardization guidelines for the assessment of cut marks, focusing on a comprehensive suite of microscopic cut mark characteristics commonly observed in the existing literature. The skeletal sample for the current research was derived from a previous macroscopic cut mark characteristic experiment where trauma was inflicted to 20 partially fleshed domestic pig (Sus scrofa domesticus) limbs utilizing four chopping/hacking tools (i.e., axe, hatchet, machete, and cleaver) as well as a large carving knife for comparison. Cut marks were evaluated for 15 microscopic cut mark characteristics to assess statistical significance. Utilizing a chi-square analysis, nine of the 15 microscopic cut mark characteristics demonstrated statistically significant differences in relation to the tool utilized, indicating moderate to relatively strong effect sizes. For example, it should be possible to use a combination of microscopic cut mark characteristics to potentially indicate which chopping/hacking tool inflicted trauma when analyzing bones. In particular, examining the characteristics such as regularity of the cut mark edges along with the occurrence of uprising, fossae/depressions, and microscopic fractures can suggest or exclude tool class within forensic contexts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In forensic anthropology, osteological sex estimation methods are continuously reevaluated and updated to improve classification accuracies. Therefore, to gain a comprehensive understanding of recent trends in sex estimation research in forensic anthropology, a content analysis of articles published between 2000 and 2022 in Forensic Science International, the Journal of Forensic Sciences, the International Journal of Legal Medicine, the American Journal of Biological Anthropology, and Forensic Anthropology, was performed. The main goals of this content analysis were to (1) examine trends in metric versus morphological research, (2) examine which areas of the skeleton have been explored, (3) examine which skeletal collections and population affinities have been most frequently utilized, and (4) determine which statistical methods were commonly implemented. A total of 440 articles were coded utilizing MAXQDA and the resulting codes were exported for analysis. Statistical analyses were conducted utilizing the Cochran-Armitage and Jonckheere-Terpstra tests for trends, as well as Fisher-Freeman-Halton tests. The results demonstrate that sex estimation research published in these journals has prioritized metric over morphological methods. Further, the most utilized skeletal regions continue to be the skull and pelvis, while the most popular classification statistics continue to be discriminant function analysis and logistic regression. This study also demonstrates that a substantial portion of research has been conducted utilizing U.S. and Europe-based collections and limited populations. Based on these results, future sex estimation research must continue exploring the use of long bones and other postcranial elements, testing newer methods of analysis, as well as developing population-inclusive methods., (© 2024 American Academy of Forensic Sciences.)

Background: The rate of masculinizing chest surgery for gender affirmation continues to increase. With a paucity of literature on pathological evaluation of breast specimens in this patient population, there is a need for these data and for protocols on the handling of these specimens. Methods: A retrospective chart review was performed between 2015 and 2020 on all patients who underwent chest masculinization surgery for gender dysphoria by the senior author (J.D.K.). Inclusion criteria were any patient with sex assigned female at birth who underwent removal of breast and/or nipple areolar complex tissue for gender affirmation. Patient demographics were recorded. Bilateral breast tissue was sent for routine pathology in all cases and findings were recorded. A p -value of <0.05 was considered significant. Results: Seventy-four consecutive patients and 148 breast specimen reports were identified from a database and included in the study. The mean age was 26 years (15-49). Thirty-nine patients had a known history of chest wall binding and 60 patients had undergone preoperative androgen therapy. There was no invasive or in situ carcinoma found in any breast tissue specimens. Thirty-four patients had a benign lesion in one or both breast specimens. Atypical lobular hyperplasia was found in one patient's specimen. A history of chest wall binding was not correlated with any benign lesions ( p =0.79) or stromal fibrosis ( p =0.94). A history of testosterone use was not correlated with any benign lesions ( p =0.35) or stromal fibrosis ( p =0.20). Conclusions: The prevalence (1.4%) of significant breast pathology and of benign findings (46%) in our study closely correlates with the rates in the literature. We found no correlation between significant breast pathology or benign lesions and a history of chest wall binding or preoperative androgen therapy. We recommend all breast specimens removed during chest masculinization surgery be sent for pathological evaluation., Competing Interests: No competing financial interests exist., (Copyright 2021, Mary Ann Liebert, Inc., publishers.)

Chest masculinization for gender affirmation is the removal of breast tissue and excess skin, often with repositioning of the nipple areola complexes to achieve a male-appearing chest. A double-incision technique with free nipple grafting (FNG) is the preferred method for trans men with large, ptotic breasts. The authors present the outcomes of 72 consecutive chest masculinization cases using this technique., Methods: A retrospective chart review was performed between 2015 and 2020 on all patients who underwent chest masculinization surgery for gender dysphoria by the senior author (JDK). Patients who underwent masculinization by concentric circle or liposuction-only techniques were excluded. Potential risk factors for complications were analyzed with Chi-square and logistic regression techniques. P < 0.05 was considered significant., Results: Seventy-two patients underwent bilateral mastectomy with free nipple grafting. There were 6 major complications resulting in return to operating room, re-admission, or need for interventional procedure. These included 4 hematomas, 1 infection, and 1 hospital admission for shortness of breath and pain.Minor complications treated conservatively included 3 seromas, 1 instance of delayed wound healing, 1 case of superficial thrombophlebitis, and 4 hypertrophic scars. Eleven patients experienced nipple areolar complex complications. Four patients underwent revision surgery. Nicotine use was associated with a higher rate of hematoma ( χ 2: 9.95, P = 0.007). Later operative date, a surrogate for experience, was associated with decreased return to the operating room (Odds ratio: 0.99, P = 0.025)., Conclusion: Double-incision chest contouring with free nipple grafting provides good chest contour for transgender men,with low complication rates., Competing Interests: Disclosure: The authors have no financial interests to declare in relation to the content of this article. There are no conflicts of interest to report., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Intraoral defects after tumor resection are often reconstructed with free tissue transfer. However, in patients who are not good candidates for free tissue transfer, regional flaps based on the superficial temporal artery can be utilized. The authors present our technique to reconstruct intraoral defects with the superficial temporal artery perforator (STAP) flap and early outcomes., Methods: Five patients underwent STAP flaps for defects including the hard palate, buccal sulcus, floor of mouth, and retromolar trigone between 2017 and 2019. The mean defect size was 5.6 × 3.4 cm 2 (3 × 3 cm 2 - 7 × 4 cm 2 ). The mean age was 74 (57-88) and all patients had recurrent cancer. External Doppler, indocyanine green laser angiography, and FLIR thermal imaging were used intra-operatively to identify the best perforators and plan for flap design., Results: The mean flap size was 7.6 × 3.5 cm 2 (6 × 3 cm 2 - 10 × 5 cm 2 ). Four flaps were based off of the posterior branch of the STA, while the fifth was based off of the anterior branch. Two donor sites were closed primarily, and three required skin grafts. One patient experienced partial flap necrosis. There were no complete flap losses and no donor site complications. Average follow up was 14.6 months (9-20 months). All patients maintained preoperative level of speech, mastication, and oral continence., Conclusions: The STAP flap can be based on the anterior or posterior branch of the superficial temporal artery and is a useful regional flap for intraoral defects after tumor resection., (© 2020 Wiley Periodicals LLC.)

Background: We describe a novel research database development project to increase resident and medical student scholarly ability and mentorship skills. We collected data on 3147 facial fractures treated at our institution over a 12-year period. This data was used to publish novel research on multiple types of facial fractures and outcomes., Methods: We learned about key database aspects that led to its high level of research quality and output volume through over 6 years of database development and expanded research output. A retrospective review was completed to compile the total research produced during this time period., Results: Research resulted in 20 manuscripts, 17 podium presentations, and 11 posters. 16 medical students, 5 residents and 3 faculty members were authors on at least one project. The average number of published manuscripts was 5.17 overall and 2.9, 7.0, and 14.0 for medical students, residents, and faculty, respectively. Four residents matched into fellowship, 7 medical students matched into residency, and one faculty member was promoted academically., Conclusions: A database focused on a common and under-researched pathology can result in a high volume of novel research output. Additional program benefits include increased scholarly and mentorship ability in engaged residents and medical students., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to examine a level 1 trauma center's 12-year experience treating frontal sinus fractures with regards to patient demographics, management strategies, and treatment outcomes., Methods: An institutional review board-approved retrospective review of all facial fractures at a level 1 trauma center was performed for the years 2000 to 2012. Patient demographics, location of fractures, concomitant injuries, use of antibiotics, surgical management strategies and outcomes were collected for all frontal sinus fractures. A significance value of 5% was used., Results: There were 291 frontal sinus fractures treated at our institution. The mean age of patients was 34.4 years with a male predominance (90%). The most common mechanisms of injury were assault in 82 (28.2%) and motor vehicle accidents in 80 (27.5%). Anterior table fractures were seen in 261 patients (89.7%) and posterior table fractures were seen in 181 (62.2%). Treatment included ORIF with sinus preservation in 18 (6.2%), ORIF with sinus obliteration in 20 (6.9%), and cranialization in 18 (6.2%). Antibiotics were started on admission in 152 patients (52.2%). Fatality occurred in 9.3% of patients and complications included meningitis (1%), frontal sinusitis (1%), early wound infection (0.3%), and mucopyelocele (0.3%)., Conclusions: Frontal sinus fractures in our center are most often caused by interpersonal violence. Anterior table fractures were more common than posterior table fractures and ORIF with sinus obliteration was the most common surgical intervention. Most frontal sinus fractures at our institution (82%) were treated conservatively with no surgical intervention and we observed a low rate of long term complications.

Objectives: The Baltic region, particularly Lithuania, was a politically vibrant area of Eastern Europe during the medieval and early modern period. To better understand the diet of Lithuanians during the late 14th to early 18th century, we examine stable carbon and nitrogen isotope ratios from bone and dentin samples from the site of Alytus. We investigate possible dietary differences based on sex, age, and religious practice, as well as dietary changes throughout an individual's lifetime, within the broader European milieu., Materials and Methods: Stable carbon and nitrogen isotope analysis was conducted on bone (n = 35) and dentin (n = 38) collagen samples from a total of 39 individuals buried in the cemetery at Alytus (late 14th to early 18th centuries)., Results: Results indicate individuals at Alytus consumed a C 3 terrestrial based diet. The δ 13 C and δ 15 N values are not significantly different between bone and dentin, and did not vary by sex., Discussion: The diet at Alytus was homogeneous between males and females and between tissue types. The lack of evidence indicating substantial consumption of fish is unexpected given widespread Catholic fasting practices and marine resource trade throughout Europe. Comparisons with other populations indicate that individuals from Alytus differ in diet from contemporaneous Polish-Lithuanian Commonwealth elites. Comparison of the diets of non-elite individuals in the Eastern Baltic region also reveals dietary variability., (© 2018 Wiley Periodicals, Inc.)

Objective: Indocyanine green laser angiography utilizes fluorescent dye to assess tissue perfusion in real time. While various studies have recommended against the concurrent use of indocyanine green angiography with vasoconstrictors, few studies have described the intraoperative effect of tumescent wetting solutions on indocyanine green angiography and its subsequent impact on scan interpretation and clinical decision-making. Methods: A retrospective medical record review was performed for cases in which indocyanine green angiography was utilized to assess an area where epinephrine-based tumescent solution had been used. Results: The authors report 2 cases that utilized epinephrine-based tumescent solution along with intraoperative indocyanine green angiography assessment of the region. The first case was a bilateral reduction mammoplasty, whereas the second case was a nipple-sparing mastectomy with immediate tissue expander reconstruction. In both cases, intraoperative angiography predicted poor tissue perfusion while clinical examination showed good perfusion. Clinical examination was followed in both cases, with no additional tissue being removed. Neither case resulted in tissue necrosis despite angiography results. Conclusions: While indocyanine green angiography is a powerful tool in tissue perfusion assessment, there are some situations in which clinical examination must be used to determine tissue viability.

Regardless of region, skeletal remains deposited in subaerial contexts are subjected to a progression of taphonomic alterations. However, there are limited postmortem interval (PMI) standards developed, particularly in environments where skeletonization can occur quickly. The research purpose was to evaluate the timing and progression of early weathering alterations in two microenvironments (shaded and open) using pig carcasses (Sus scrofa) in the subtropical humid environment of central Florida. Over nine months, sun bleaching was assessed using Munsell ® Soil Color Charts (2009) and scored based on percentage of the bone sun bleached, while bone weathering was further evaluated using Behrensmeyer's (1978) stages. Results indicate that microenvironment has a significant influence, with the onset and progression of sun bleaching and Behrensmeyer's (1978) Stages 2 and 3 occurring earlier in the open microenvironment. Sun bleaching stages and Behrensmeyer's (1978) weathering stages can be utilized in conjunction for developing regionally specific PMI taphonomic models for different microenvironments., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Scavengers can significantly alter a forensic scene and consume, modify, disarticulate, and disperse bodies on the ground surface. The research purpose was to examine vulture scavenging in central Florida, USA. Four small-sized pig (Sus scrofa) carcasses were left on the ground surface of two microenvironments (shaded and open) at a secure site with game cameras. Dispersal data were mapped and analyzed using geographical information systems spatial analysis digital mapping tools. The primary avian scavengers recorded included black vultures (Coragyps atratus) and turkey vultures (Cathartes aura), as well as bald eagles (Haliaeetus leucocephalus). Carcass dispersal patterns were impacted by foliage density (grass height and concentrations of bushes and trees) and proximity to the perimeter fence. While the majority of skeletal elements were dispersed within 6 m of the carcass deposition locations, dispersion occurred over a greater distance in the wooded microenvironment. Overall, vulture behaviors deleteriously destroyed and changed the context of the scene, with black vultures having the greatest impact., (© 2017 American Academy of Forensic Sciences.)

It is important to conduct timing of injury research analyzing fracture characteristics at known postmortem intervals (PMI) because bone can retain fresh characteristics throughout the PMI. Defleshed pig (Sus scrofa) long bones were fractured weekly in two environments (full sun and shade) over 14 weeks in Central Florida and fracture characteristics were categorized (N = 136) for analysis. Results of analysis of variance (ANOVA) using time in weeks (PMI) as a dependent variable indicate significant relationships between PMI and Fracture Angle (p < 0.001), Fracture Surface (p < 0.001), and Fracture Outline (p < 0.001). Fracture characteristics associated with perimortem trauma (smooth Fracture Surfaces and curved or V-shaped Fracture Outlines) were commonly observed. Analysis of fracture characteristics for each environment demonstrated similar patterns. Overall, the loss of only fresh fracture characteristics for each bone was noted earlier in the PMI for the Central Florida region than previously reported., (© 2016 American Academy of Forensic Sciences.)

Cardiac foreign bodies are rare in children and the nature or timing of the injury may be hard to ascertain. We report a case of a 10-year-old boy who presented with a 28-mm solid core needle in the left chest wall that advanced into his right ventricle, possibly from soft tissue manipulation. Computed tomography, intraoperative fluoroscopy, and echocardiography were necessary to locate the needle and successfully remove it surgically., (© The Author(s) 2016.)

Identification of osseous materials is generally established on gross anatomical features. However, highly fragmented or taphonomically altered materials may be problematic and may require chemical analysis. This research was designed to assess the use of scanning electron microscopy-energy-dispersive X-ray spectrometry (SEM/EDX), elemental analysis, and multivariate statistical analysis (principal component analysis) for discrimination of osseous and nonosseous materials of similar chemical composition. Sixty samples consisting of osseous (human and nonhuman bone and dental) and non-osseous samples were assessed. After outliers were removed a high overall correct classification of 97.97% was achieved, with 99.86% correct classification for osseous materials. In addition, a blind study was conducted using 20 samples to assess the applicability for using this method to classify unknown materials. All of the blind study samples were correctly classified resulting in 100% correct classification, further demonstrating the efficiency of SEM/EDX and statistical analysis for differentiation of osseous and nonosseous materials., (© 2015 American Academy of Forensic Sciences.)

Forensic investigators routinely deploy side-scan sonar for submerged body searches. This study adds to the limited body of literature by undertaking a controlled project to understand how variables affect detection of submerged bodies using side-scan sonar. Research consisted of two phases using small and medium-sized pig (Sus scrofa) carcasses as proxies for human bodies to investigate the effects of terrain, body size, frequency, swath width, and state of decomposition. Results demonstrated that a clear, flat, sandy pond floor terrain was optimal for detection of the target as irregular terrain and/or vegetation are major limitations that can obscure the target. A higher frequency towfish was preferred for small bodies, and a 20 m swath width allowed greater visibility and easier maneuverability of the boat in this environment. Also, the medium-sized carcasses were discernable throughout the 81-day study period, indicating that it is possible to detect bodies undergoing decomposition with side-scan sonar., (© 2015 American Academy of Forensic Sciences.)

Forensic anthropologists are generally able to identify skeletal materials (bone and tooth) using gross anatomical features; however, highly fragmented or taphonomically altered materials may be problematic to identify. Several chemical analysis techniques have been shown to be reliable laboratory methods that can be used to determine if questionable fragments are osseous, dental, or non-skeletal in nature. The purpose of this review is to provide a detailed background of chemical analysis techniques focusing on elemental compositions that have been assessed for use in differentiating osseous, dental, and non-skeletal materials. More recently, chemical analysis studies have also focused on using the elemental composition of osseous/dental materials to evaluate species and provide individual discrimination, but have generally been successful only in small, closed groups, limiting their use forensically. Despite significant advances incorporating a variety of instruments, including handheld devices, further research is necessary to address issues in standardization, error rates, and sample size/diversity., (Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.)

One of the tasks of a forensic anthropologist is to sort human bone fragments from other materials, which can be difficult when dealing with highly fragmented and taphonomically modified material. The purpose of this research is to develop a method using handheld X-ray fluorescence (HHXRF) spectrometry to distinguish human and nonhuman bone/teeth from nonbone materials of similar chemical composition using multivariate statistical analyses. The sample materials were derived primarily from previous studies: human bone and teeth, nonhuman bone, nonbiological materials, nonbone biological materials, and taphonomically modified materials. The testing included two phases, testing both the reliability of the instrument and the accuracy of the technique. The results indicate that osseous and dental tissue can be distinguished from nonbone material of similar chemical composition with a high degree of accuracy (94%). While it was not possible to discriminate rock apatite and synthetic hydroxyapatite from bone/teeth, this technique successfully discriminated ivory and octocoral., (© 2015 American Academy of Forensic Sciences.)

Forensic personnel must deal with numerous challenges when searching for submerged objects. While traditional water search methods have generally involved using dive teams, remotely operated vehicles (ROVs), and water scent dogs for cases involving submerged objects and bodies, law enforcement is increasingly integrating multiple methods that include geophysical technologies. There are numerous advantages for integrating geophysical technologies, such as side scan sonar and ground penetrating radar (GPR), with more traditional search methods. Overall, these methods decrease the time involved searching, in addition to increasing area searched. However, as with other search methods, there are advantages and disadvantages when using each method. For example, in instances with excessive aquatic vegetation or irregular bottom terrain, it may not be possible to discern a submersed body with side scan sonar. As a result, forensic personnel will have the highest rate of success during searches for submerged objects when integrating multiple search methods, including deploying multiple geophysical technologies. The goal of this paper is to discuss the methodology of various search methods that are employed for submerged objects and how these various methods can be integrated as part of a comprehensive protocol for water searches depending upon the type of underwater terrain. In addition, two successful case studies involving the search and recovery of a submerged human body using side scan sonar are presented to illustrate the successful application of integrating a geophysical technology with divers when searching for a submerged object., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Scene mapping is an integral aspect of processing a scene with scattered human remains. By utilizing the appropriate mapping technique, investigators can accurately document the location of human remains and maintain a precise geospatial record of evidence. One option that has not received much attention for mapping forensic evidence is the differential global positioning (DGPS) unit, as this technology now provides decreased positional error suitable for mapping scenes. Because of the lack of knowledge concerning this utility in mapping a scene, controlled research is necessary to determine the practicality of using newer and enhanced DGPS units in mapping scattered human remains. The purpose of this research was to quantify the accuracy of a DGPS unit for mapping skeletal dispersals and to determine the applicability of this utility in mapping a scene with dispersed remains. First, the accuracy of the DGPS unit in open environments was determined using known survey markers in open areas. Secondly, three simulated scenes exhibiting different types of dispersals were constructed and mapped in an open environment using the DGPS. Variables considered during data collection included the extent of the dispersal, data collection time, data collected on different days, and different postprocessing techniques. Data were differentially postprocessed and compared in a geographic information system (GIS) to evaluate the most efficient recordation methods. Results of this study demonstrate that the DGPS is a viable option for mapping dispersed human remains in open areas. The accuracy of collected point data was 11.52 and 9.55 cm for 50- and 100-s collection times, respectfully, and the orientation and maximum length of long bones was maintained. Also, the use of error buffers for point data of bones in maps demonstrated the error of the DGPS unit, while showing that the context of the dispersed skeleton was accurately maintained. Furthermore, the application of a DGPS for accurate scene mapping is discussed and guidelines concerning the implementation of this technology for mapping human scattered skeletal remains in open environments are provided., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Thyroid hormone receptor (TR) α and β mediate thyroid hormone action at target tissues. TR isoforms have specific roles in development and in adult tissues. The mechanisms underlying TR isoform-specific action, however, are not well understood. We demonstrate that posttranslational modification of TR by conjugation of small SUMO to TRα and TRβ plays an important role in triiodothyronine (T3) action and TR isoform specificity. TRα was sumoylated at lysines 283 and 389, and TRβ at lysines 50, 146, and 443. Sumoylation of TRβ was ligand-dependent, and sumoylation of TRα was ligand-independent. TRα-SUMO conjugation utilized the E3 ligase PIASxβ and TRβ-SUMO conjugation utilized predominantly PIAS1. SUMO1 and SUMO3 conjugation to TR was important for T3-dependent gene regulation, as demonstrated in transient transfection assay and studies of endogenous gene regulation. The functional role of SUMO1 and SUMO3 in T3 induction in transient expression assays was closely matched to the pattern of TR and cofactor recruitment to thyroid hormone response elements (TREs) as determined by ChIP assays. SUMO1 was required for the T3-induced recruitment of the co-activator CREB-binding protein (CBP) and release of nuclear receptor co-repressor (NCoR) on a TRE but had no significant effect on TR DNA binding. SUMO1 was required for T3-mediated recruitment of NCoR and release of CBP from the TSHβ-negative TRE. SUMO3 was required for T3-stimulated TR binding to the TSHβ-negative TRE and recruitment of NCoR. These findings demonstrate that conjugation of SUMO to TR has a TR-isoform preference and is important for T3-dependent gene induction and repression.

Morphological traits of the posterior ilium are commonly used for sex determination in bioarcheological and forensic skeletal analysis. This study was designed to compare the classification correctness of standard scoring systems and measurements of the posterior ilium, including using logistic regression, to develop new formulae to predict sex. Metric measurements and morphological scores for the preauricular sulcus (PS), the elevation of the auricular surface, and the greater sciatic notch width were recorded for 97 males and 101 females of both European and African ancestry from the William M. Bass and Terry Collections. Correct classification of sex was high using individual traits such as the greater sciatic notch score (88.4%), the presence or absence of a PS (78.8%), and the scoring of a present PS as 1, 2, or 3 (100%). Furthermore, an equation combining multiple traits of the posterior ilium had a high classification of 94.9%., (© 2012 American Academy of Forensic Sciences.)

Forensic personnel generally use basic all-metal detectors for weapon searches because of their ease of use and cost efficiency. For ferromagnetic targets, an alternative easy to use and low-cost geophysical tool is a magnetic locator. The following study was designed to demonstrate the effectiveness of a common, commercially available magnetic locator in forensic weapon searches by determining the maximum depth of detection for 32 metallic forensic targets and testing the effects of metallic composition on detection. Maximum depth of detection was determined for 16 decommissioned street-level firearms, six pieces of assorted scrap metals, and 10 blunt or bladed weapons by burying each target at 5-cm intervals until the weapons were no longer detected. As expected, only ferromagnetic items were detected; weapons containing both ferromagnetic and nonferromagnetic components were generally detected to shallower depths. Overall, the magnetic locator can be a useful addition to weapon searches involving buried ferromagnetic weapons., (© 2011 American Academy of Forensic Sciences.)

Since ground-penetrating radar (GPR) has become a popular search option for clandestine graves, controlled research is essential to determine the numerous variables that affect grave detection. The purpose of this study was to compare GPR reflection profiles of a controlled grave containing a large pig carcass and a blank control grave at 6 months interment in a Spodosol, which is a common soil type in Florida. Data collection was performed in perpendicular orientations over the graves using both 500 and 250 MHz antennae. Since reflection profiles are used to make initial in-field assessments during a forensic search, it is important for controlled research to evaluate this imagery option. Overall, it was possible to detect the grave containing a pig carcass at 6 months interment that was buried in a Spodosol using both the 500 and the 250 MHz antennae. While the 500 MHz antenna provided more detail within the grave containing a pig carcass, including detecting a soil disturbance and the pig carcass, the 250 MHz antenna also provided excellent imagery. Either antenna would provide optimal results for the type of soil that was sampled. Furthermore, it may be possible to locate actual forensic graves in this soil type when no response from the body is noted, as there may be a discernable response from the disturbed soil within the grave shaft and a noticeable disruption of the spodic horizon. Finally, survey orientation may also affect detection. Since data collection performed in two perpendicular directions detected the pig carcass and the grave floor of the control grave, data collection for an actual search involving a body interred for a long postmortem interval should be performed in both directions when time permits., (Published by Elsevier Ireland Ltd.)

Forensic personnel may face a daunting task when searching for buried weapons at crime scenes or potential disposal sites. In particular, it is common to search for a small firearm that was discarded or buried by a perpetrator. When performing forensic searches, it is recommended to first use non-invasive methods such as geophysical instruments to minimize damage to evidence and to the crime scene. Geophysical tools are used to pinpoint small areas of interest across a scene for invasive testing, rather than digging large areas throughout the site. Prior to this project, there was no published research that tested the utility of the conductivity meter to search for metallic weapons such as firearms and blunt and sharp edged weapons. A sample comprised of 32 metallic weapons including firearms, blunt and sharp edged weapons, and scrap metals was buried in a controlled setting to test the applicability of a conductivity meter for forensic searches. Weapons were tested at multiple depths and after data collection was performed for one depth, the weapons were reburied 5 cm deeper until they were no longer detected. Variables such as weapon size, burial depth, transect interval spacing (25 and 50 cm), and metallic composition were tested. All of the controlled variables influenced maximum depth of detection. For example, size was a factor as larger weapons were detected at deeper depths compared to smaller weapons. Metal composition affected maximum depth of detection as the conductivity meter detected items comprised of ferrous metals at deeper depths than non-ferrous metals. Searches for large buried items may incorporate a transect interval spacing of 50 cm but small weapons may be undetected between transects and therefore a transect interval spacing of 25 cm is recommended. Overall, the conductivity meter is a geophysical tool to consider when searching for larger-sized metallic weapons or to use in conjunction with an all-metal detector, particularly when searching for buried metallic evidence in obstructed areas., (Published by Elsevier Ireland Ltd.)

Incorporating geophysical technologies into forensic investigations has become a growing practice. Oftentimes, forensic professionals rely on basic metal detectors to assist their efforts during metallic weapons searches. This has created a need for controlled research in the area of weapons searches, specifically to formulate guidelines for geophysical methods that may be appropriate for locating weapons that have been discarded or buried by criminals attempting to conceal their involvement in a crime. Controlled research allows not only for testing of geophysical equipment, but also for updating search methodologies. This research project was designed to demonstrate the utility of an all-metal detector for locating a buried metallic weapon through detecting and identifying specific types of buried metal targets. Controlled testing of 32 buried targets which represented a variety of sizes and metallic compositions included 16 decommissioned street-level firearms, 6 pieces of assorted scrap metals, and 10 blunt or bladed weapons. While all forensic targets included in the project were detected with the basic all-metal detector, the size of the weapon and surface area were the two variables that affected maximum depth of detection, particularly with the firearm sample. For example, when using a High setting the largest firearms were detected at a maximum depth of 55 cm, but the majority of the remaining targets were only detected at a maximum depth of 40 cm or less. Overall, the all-metal detector proved to be a very good general purpose metal detector best suited for detecting metallic items at shallow depths., (2009 Elsevier Ireland Ltd. All rights reserved.)

Cold-induced adaptive (or nonshivering) thermogenesis in small mammals is produced primarily in brown adipose tissue (BAT). BAT has been identified in humans and becomes more active after cold exposure. Heat production from BAT requires sympathetic nervous system stimulation, T(3), and uncoupling protein 1 (UCP1) expression. Our previous studies with a thyroid hormone receptor-beta (TR beta) isoform-selective agonist demonstrated that after TR beta stimulation alone, adaptive thermogenesis was markedly impaired, although UCP-1 expression in BAT was normal. We used mice with a dominant-negative TR beta PV mutation (frameshift mutation in resistance to thyroid hormone patient PV) to determine the role of TR beta in adaptive thermogenesis and UCP1 expression. Wild-type and PV mutant mice were made hypothyroid and replaced with T(3) (7 ng/g x d) for 10 d to produce similar serum thyroid hormone concentration in the wild-type and mutant mice. The thermogenic response of interscapular BAT, as determined by heat production during iv infusions of norepinephrine, was reduced in PV beta heterozygous and homozygous mutant mice. The level of UCP1, the key thermogenic protein in BAT, was progressively reduced in PV beta(+/-) and PV beta(-/-) mutant mice. Brown adipocytes isolated from PV mutant mice had some reduction in cAMP and glycerol production in response to adrenergic stimulation. Defective adaptive thermogenesis in TR beta PV mutant mice is due to reduced UCP1 expression and reduced adrenergic responsiveness. TR beta mediates T(3) regulation of UCP1 in BAT and is required for adaptive thermogenesis.

Ground-penetrating radar (GPR) was used to monitor 12 pig burials in Florida, each of which contained a small pig cadaver. Six of the cadavers were buried in sand at a depth of 0.50-0.60 m, and the other six were buried in sand at a depth of 1.00-1.10 m to represent deep and shallow burials that are generally encountered in forensic scenarios. Four control excavations with no pig interment were also constructed as blank graves and monitored with GPR. The burials were monitored for durations of either 13 or 21 months, and were then excavated to correlate the decomposition state of the cadaver with the GPR imagery. Overall, this study demonstrated that it may be difficult to detect small cadavers buried in sand soon after they are skeletonized because the area surrounding the body, or the grave, may not provide a strong enough contrasting area to be detected by GPR when compared to that of the surrounding undisturbed soil. Also, depth of burial appears to influence grave detection because bodies that are buried at deeper depths may be detected for a longer period of time due to reduced decomposition rates.

Thyroid hormone regulates the balance between lipolysis and lipogenesis. We previously reported that male mice with a dominant-negative P398H mutation introduced into the TRalpha gene have visceral obesity, hyperleptinemia, and reduced catecholamine-stimulated lipolysis in white adipose tissue. Based on our observation of hepatic steatosis in the TRalpha P398H male mice, we used in vitro and in vivo models to investigate the influence of the TRalpha P398H mutant on peroxisome proliferator-activated receptor-alpha (PPARalpha) signaling. Wild-type TRalpha and the P398H mutant significantly reduced PPARalpha-mediated transcription in transient transfection assays. T(3) reversed the inhibition of PPARalpha action by wild-type TRalpha but not the P398H mutant. Chromatin immunoprecipitation assays demonstrated that the P398H mutant reduces PPARalpha binding to peroxisome proliferator receptor elements. In gel shift assays, the P398H mutant directly bound the peroxisome proliferator-activated receptor response element and inhibited PPARalpha binding, which was not reversed by addition of retinoid X receptor. The TRalpha R384C and PV dominant-negative mutants are not associated in vivo with a metabolic phenotype and had reduced (PV) or absent (R384C) PPARalpha inhibition compared with P398H. The metabolic phenotype of the P398H mutant mice is due, in part, to unique properties of the P398H mutant receptor interfering with PPARalpha signaling. The P398H mutant is a potential probe to characterize the physiological role of thyroid hormone receptor/PPARalpha interactions.

Thyroid hormone negatively regulates the amyloid-beta precursor protein (APP) gene in thyroid hormone receptor (TR)-transfected neuroblastoma cells. A negative thyroid hormone response element (nTRE) that mediates this regulation has been identified in the first exon of the APP gene. We demonstrate in an in vivo system that expression of APP mRNA, APP protein, and APP secretase cleavage products in mouse brain is influenced by thyroid status. Adult female mice were made hyperthyroid or hypothyroid for 3 weeks and compared to euthyroid mice. APP gene product expression was increased in hypothyroid mouse brain and reduced in hyperthyroid mouse brain, when compared to euthyroid controls. We observed similar effects of thyroid hormone on endogenous APP gene expression in human neuroblastoma cells. The incidence of hypothyroidism increases with age, and localized hypothyroidism of central nervous system has been reported in some patients with Alzheimer's disease (AD). Reduced action of thyroid hormone on the APP gene may contribute to AD pathology by increasing APP expression and the levels of processed APP products. These findings may be an underlying mechanism contributing to the association of hypothyroidism with AD in the elderly, as well as identifying a potential therapeutic target. Pharmacologic supplementation of thyroid hormone, or its analogs, may reduce APP gene expression and beta amyloid peptide accumulation.

Ground-penetrating radar (GPR) was used to monitor 12 pig burials in Florida, each of which contained a large pig cadaver. Six of the cadavers were buried in sand at a depth of 0.50-0.60 m, and the other six were buried at a depth of 1.00-1.10 m and were in contact with the upper surface of a clay horizon. Control excavations with no pig internment were also constructed as blank graves and monitored with GPR. The burials were monitored with GPR for durations of either 12-13 or 21-21.5 months when they were then excavated to correlate the decomposition state of the cadaver with the GPR imagery. Overall, cadavers in sand were easily detected for the duration of this study at 21.5 months, even when completely skeletonized. Conversely, in clay it became increasingly difficult to image the pig cadavers over the first year of burial, even when they still retained extensive soft tissue structures.

Lactating breast tissue and some breast cancers express the sodium/iodide symporter (NIS) and concentrate iodide. We recently demonstrated that all-trans retinoic acid (tRA) induces both NIS gene expression and iodide accumulation in vitro in well-differentiated human breast cancer cells (MCF-7). In the present study, we investigated the in vivo efficacy and specificity of tRA-stimulated iodide accumulation in mouse breast cancer models. Immunodeficient mice with MCF-7 xenograft tumors were treated with systemic tRA for 5 days. Iodide accumulation in the xenograft tumors was markedly increased, approximately 15-fold greater than levels without treatment, and the effects were tRA dose dependent. Iodide accumulation in other organs was not significantly influenced by tRA treatment. Significant induction of NIS mRNA and protein in the xenograft tumors was observed after tRA treatment. Iodide accumulation and NIS mRNA expression were also selectively induced in breast cancer tissues in transgenic mice expressing the oncogene, polyoma virus middle T antigen. These data demonstrate selective induction of functional NIS in breast cancer by tRA. Treatment with short-term systemic retinoic acid, followed by radioiodide administration, is a potential tool in the diagnosis and treatment of some differentiated breast cancer.

Thyroid hormone has profound effects on metabolic homeostasis, regulating both lipogenesis and lipolysis, primarily by modulating adrenergic activity. We generated mice with a point mutation in the thyroid hormone receptor alpha (TRalpha) gene producing a dominant-negative TRalpha mutant receptor with a proline to histidine substitution (P398H). The heterozygous P398H mutant mice had a 3.4-fold (p < 0.02) increase in serum thyrotropin (TSH) levels. Serum triiodothyronine (T3) and thyroxine (T4) concentrations were slightly elevated compared with wild-type mice. The P398H mice had a 4.4-fold increase in body fat (as a fraction of total body weight) (p < 0.001) and a 5-fold increase in serum leptin levels (p < 0.005) compared with wild-type mice. A 3-fold increase in serum fasting insulin levels (p < 0.002) and a 55% increase in fasting glucose levels (p < 0.01) were observed in P398H compared with wild-type mice. There was a marked reduction in norepinephrine-induced lipolysis, as reflected in reduced glycerol release from white adipose tissue isolated from P398H mice. Heart rate and cold-induced adaptive thermogenesis, mediated by thyroid hormone-catecholamine interaction, were also reduced in P398H mice. In conclusion, the TRalpha P398H mutation is associated with visceral adiposity and insulin resistance primarily due to a marked reduction in catecholamine-stimulated lipolysis. The observed phenotype in the TRalpha P398H mouse is likely due to interference with TRalpha action as well as influence on other metabolic signaling pathways. The physiologic significance of these findings will ultimately depend on understanding the full range of actions of this mutation.

During the winter of 1778-1779, a garrison of 176 individuals lived within the walls of a Revolutionary era stronghold named Ft. Laurens on the banks of the Tuscarawas River, near the present-day town of Bolivar, Ohio. At least 21 individuals were buried in the fort's cemetery during its occupation, 13 of whom were supposedly killed and scalped by Native Americans while gathering firewood and foraging horses. The purpose of this study is to build on previous work by Sciulli and Gramly ([1989] Am J. Phys. Anthropol. 80:11-24) by adding a more detailed analysis of the traumatic lesions, in order to better understand what happened to the victims. Lesions were analyzed based on type, location, and dimensions, as well as their overall pattern on the skeleton. Results indicate that multiple blows to the cranium were common. Out of 12 observable crania, the order of blows could be determined in only one case. Eleven of 12 of the observable crania from ambush victims and four of the seven nonambush victims exhibited lesions consistent with scalping. Evidence of postcranial trauma was noted on four individuals: one was an ambush victim, and the other three were killed at other times. No evidence of gunshot wounds was found., (Copyright 2003 Wiley-Liss, Inc.)

Thyroid hormone plays an important role in bone development and metabolism. We used a polymerase chain reaction (PCR)-based mRNA differential display (DD) analysis to obtain a profile of thyroid hormone-responsive genes in osteoblast-like cells (ROS 17/2.8). ROS 17/2.8 cells were treated with 10(-8) M triiodothyronine (T(3)) for 2 and 24 hours. Total RNA was isolated, reverse-transcribed, and amplified using a total of 72 combinations (2 hours) and 240 combinations (24 hours) of 5' and 3' primers. At the 2-hour time point, 1 true-positive novel clone was identified and shown to be the mitochondrial gene, subunit 6 of ATP synthase (ATPase-6). At the 24-hour time point, 3 differentially expressed (DE) mRNAs were confirmed as true-positives including; nonmuscle alkali myosin light chain (NM aMLC), ATPase-6, and one novel clone. T(3)-induction of ATPase-6 mRNA in ROS 17/2.8 cells was seen at 2 and 4 hours, but was maximal at 24 hours (2.1-fold). T(3) induction of ATPase-6 mRNA was increased to fourfold in ROS 17/2.8 cells cultured at a low density. NM aMLC mRNA was modestly upregulated by T(3) in ROS 17/2.8 cells by 1.4-fold, and induction was augmented at low cell density to 1.7-fold. T(3) action on NM aMLC and on the mitochondrial gene ATPase 6, represent novel targets and potential mediators of thyroid hormone action on bone. Cell type, and the extent of cell differentiation, influences T(3) regulation of genes in osteoblast-derived cells.

Contemporary commercial cremation is a reductive taphonomic process that represents one of the most extreme examples of postmortem human alteration of bone. The thorough reduction and fragmentation of cremated human remains often leaves little biological evidence of diagnostic value. Instead, non-osseous artifacts often provide the best evidence of the origin of the cremated remains, the identity of the decedent, and commingling of the remains of more than one individual. Once human remains have been cremated they are most commonly placed into a processor and reduced into small fragments and fine ash suitable for inurnment or scattering. The type of processor determines the size and utility of the particulates and artifacts available for analysis. The newest type of processors have changed the manner and degree of postmortem bone modification and altered the preservation of diagnostic bone fragments and cremation artifacts. This paper addresses the impact of the newest cremation procedures on forensic analysis of cremated remains.

Several polymerase chain reaction (PCR)-based methods have recently been developed for diagnosing malarial infections in both birds and reptiles, but a critical evaluation of their sensitivity in experimentally-infected hosts has not been done. This study compares the sensitivity of several PCR-based methods for diagnosing avian malaria (Plasmodium relictum) in captive Hawaiian honeycreepers using microscopy and a recently developed immunoblotting technique. Sequential blood samples were collected over periods of up to 4.4 yr after experimental infection and rechallenge to determine both the duration and detectability of chronic infections. Two new nested PCR approaches for detecting circulating parasites based on P. relictum 18S rRNA genes and the thrombospondin-related anonymous protein (TRAP) gene are described. The blood smear and the PCR tests were less sensitive than serological methods for detecting chronic malarial infections. Individually, none of the diagnostic methods was 100% accurate in detecting subpatent infections, although serological methods were significantly more sensitive (97%) than either nested PCR (61-84%) or microscopy (27%). Circulating parasites in chronically infected birds either disappear completely from circulation or to drop to intensities below detectability by nested PCR. Thus, the use of PCR as a sole means of detection of circulating parasites may significantly underestimate true prevalence.

In newborns and small mammals, cold-induced adaptive (or nonshivering) thermogenesis is produced primarily in brown adipose tissue (BAT). Heat production is stimulated by the sympathetic nervous system, but it has an absolute requirement for thyroid hormone. We used the thyroid hormone receptor-beta--selective (TR-beta--selective) ligand, GC-1, to determine by a pharmacological approach whether adaptive thermogenesis was TR isoform--specific. Hypothyroid mice were treated for 10 days with varying doses of T3 or GC-1. The level of uncoupling protein 1 (UCP1), the key thermogenic protein in BAT, was restored by either T3 or GC-1 treatment. However, whereas interscapular BAT in T3-treated mice showed a 3.0 degrees C elevation upon infusion of norepinephrine, indicating normal thermogenesis, the temperature did not increase (<0.5 degrees C) in GC-1--treated mice. When exposed to cold (4 degrees C), GC-1--treated mice also failed to maintain core body temperature and had reduced stimulation of BAT UCP1 mRNA, indicating impaired adrenergic responsiveness. Brown adipocytes isolated from hypothyroid mice replaced with T3, but not from those replaced with GC-1, had normal cAMP production in response to adrenergic stimulation in vitro. We conclude that two distinct thyroid-dependent pathways, stimulation of UCP1 and augmentation of adrenergic responsiveness, are mediated by different TR isoforms in the same tissue.

The sodium/iodide symporter (NIS) stimulates iodide uptake in normal lactating breast, but is not known to be active in nonlactating breast or breast cancer. We studied NIS gene regulation and iodide uptake in MCF-7 cells, an estrogen receptor (ER)-positive human breast cancer cell line. All-trans retinoic acid (tRA) treatment stimulated iodide uptake in a time- and dose-dependent fashion up to approximately 9.4-fold above baseline. Stimulation with selective retinoid compounds indicated that the induction of iodide uptake was mediated by retinoic acid receptor. Treatment with tRA markedly stimulated NIS mRNA and immunoreactive protein ( approximately 68 kDa). tRA stimulated NIS gene transcription approximately 4-fold, as shown by nuclear run-on assay. No induction of iodide uptake was observed with RA treatment of an ER-negative human breast cancer cell line, MDA-MB 231, or a normal human breast cell line, MCF-12A. The iodide efflux rate of tRA-treated MCF-7 cells was slow (t(1/2) = 24 min), compared with that in FRTL-5 thyroid cells (t(1/2) = 3.9 min), favoring iodide retention in MCF-7 cells. An in vitro clonogenic assay demonstrated selective cytotoxicity with (131)I after tRA stimulation of MCF-7 cells. tRA up-regulates NIS gene expression and iodide uptake in an ER-positive breast cancer cell line. Stimulation of radioiodide uptake after systemic retinoid treatment may be useful for diagnosis and treatment of some differentiated breast cancers.

Administration of inhibitors of the Na+/H+ exchanger (NHE) have been shown to produce cardioprotective effects in a number of animal models of ischemia-reperfusion injury; however, controversy still exists as to the efficacy of these agents when administered just before reperfusion. To address this question, the efficacy of several doses of a new selective NHE-1 isoform inhibitor (IC50 for inhibition of 22Na uptake in NHE-1 expressing mouse fibroblast cells = 10.4 +/- 1.0 nM), EMD 85131 (2-methyl-5-methylsulfonyl-1-(1-pyrrollyl)-benzoyl-guanidine), was tested in a canine infarct model in which the left anterior descending coronary artery was occluded for 60 min followed by 3 hr of reperfusion. EMD 85131 (0.75 or 3.0 mg/kg) was infused for 15 min before left anterior descending occlusion or 15 min before reperfusion. Infarct size was determined by use of the triphenyltetrazolium chloride histochemical stain and was expressed as a percent of the area at risk. EMD 85131 (0.75 or 3.0 mg/kg) administered before left anterior descending occlusion produced a marked (*P < .05) and dose-related reduction in IS/AAR (24.3 +/- 3.6, control; 9.3 +/- 3.4%, EMD 0.75; 6.4 +/- 2.3%, EMD 3.0). These two doses of EMD also produced significant (*P < .05) reductions in infarct size/area at risk (12.2 +/- 2.1%, EMD 0.75; 13.0 +/- 2.9%, EMD 3.0) when administered 15 min before reperfusion. These results suggest that selective NHE-1 inhibitors are able to markedly reduce infarct size when given before or during ischemia and also suggest that these compounds may have clinical utility when administered after the initiation of an ischemic insult.

Several investigators have demonstrated that the opioid pathway is involved in tissue preservation during hypoxia or ischemia and that this protection is mediated via the delta (delta)-opioid receptor. Subsequently, we have shown that opioid receptors are involved in ischemic preconditioning (PC) in the rat heart and that morphine produces a cardioprotective effect; however, the class of opioid receptors involved in mediating these effects is still unknown. Therefore, the purpose of the present study was to test the hypothesis that ischemia- and morphine-induced cardioprotection are mediated via stimulation of the delta-opioid receptor in the rat heart. Anesthetized, open-chest Wistar rats were subjected to one of six protocols. The control group was subjected to 30 min of occlusion and 2 h of reperfusion. Ischemic PC was elicited by three 5 min occlusion periods interspersed with 5 min of reperfusion. Morphine-induced cardioprotection was produced by three 5 min morphine infusions (100 microg/kg/infusion, i.v.) interspersed with a 5-min drug-free period. To determine if the delta-opioid receptor has a role in ischemic PC and morphine-induced cardioprotection, naltrindole (NTI), a selective delta-opioid receptor antagonist, was utilized. NTI (5 mg/kg, i.v.) was given 10 min prior to ischemic PC (NTI+PC) or morphine infusion (NTI+MOR). Also, NTI (5 mg/kg, i.v.) was given 10 min before the 30 min occlusion period in untreated rats. Infarct size (IS) as a percent of the area at risk (AAR) was determined by 2,3,5-triphenyltetrazolium chloride staining. Ischemic PC and morphine infusions resulted in similar reductions in IS/AAR from 51+/-4 to 11+/-3 and 15+/-4% (*P<0.05), respectively. NTI completely abolished the cardioprotective effect induced by ischemia and morphine. The results of the present study suggests a role of delta;-opioid receptors in ischemic PC or morphine-induced myocardial protection in the rat.

Previously, our laboratory has shown that opioid receptors are involved in ischemic preconditioning (PC) in the intact rat heart; however, it is not known whether this cardioprotection is mediated by central or peripheral mechanisms. To test this hypothesis, both naloxone (NL), the non-selective opioid receptor antagonist and naloxone methiodide (QNL), its quaternary derivative which does not cross the blood-brain barrier, were used to determine if opioid receptor-induced myocardial protection occurs via a central or peripheral locus of action in inactin-anesthetized, open-chested, Wistar rats. In group I, the control group was subjected to 30 min of occlusion and 2 h of reperfusion. In group II, ischemic PC was elicited by three 5-min occlusion periods interspersed with 5 min of reperfusion. In group III, QNL (10 mg/kg, i.v.) was administered 10 min before the 30 min of occlusion. Groups IV and V consisted of a dose-response effect of QNL on ischemic PC in which QNL (0.3 or 10 mg/kg, i.v., respectively) was given 10 min prior to ischemic PC. In addition, in groups VI and VII, one of two doses of naloxone (1 or 3 mg/kg, i.v.) was administered 10 min before ischemic PC. Infarct size (IS) as a percentage of the area at risk (AAR) was determined by tetrazolium staining. Ischemic PC reduced IS to 9 +/- 2% (P < 0.05) v control (53 +/- 4%). The low dose of QNL partially blocked the cardioprotective effect of ischemic PC; whereas the high dose completely abolished its cardioprotective effect. The high dose of QNL had no effect on IS alone. Similarly, the low dose of NL did not antagonize the cardioprotective effect of ischemic PC; however, the high dose completely abolished ischemic PC. These results indicate that the cardioprotective effect of ischemic preconditioning is mediated by a peripheral opioid receptor mechanism in the intact rat heart.

Using biochemical methods we established that estrogen receptor content and distribution and progesterone receptor content in female and male baboon myocardium did not differ between sexes. In contrast, myocardial androgen receptor distribution between cytosolic and nuclear compartments was sexually dimorphic. Female baboon myocardial androgen receptors were restricted to the cytosolic compartment, whereas male myocardial androgen receptors were distributed between the cytosolic and nuclear compartments. Using human estrogen receptor cDNA we showed that baboon aorta, myocardium and uterus contain a 6.3 kb estrogen receptor transcript. Analyses performed with human progesterone receptor cDNA established that baboon aorta and uterus contain an 8 kb progesterone receptor transcript; however, progesterone receptor transcripts were not demonstrable in baboon myocardial RNA preparations. Because relative hybridization signal intensity reflected known uterine and aortic progesterone receptor content, failure to detect progesterone receptor transcripts in myocardial preparations may reflect sensitivity limitations and the fact that aortic progesterone receptor content is 5-fold greater than that of myocardium. Immunocytochemical analyses demonstrated that baboon myocardial progesterone receptors were present in greater than 25% of myocytes and generally absent from other myocardial cells. Our studies establish that: (1) gonadal steroid hormone receptor gene transcription occurs in cells of the baboon cardiovasculature, (2) these steroid hormone receptors may be physiologically functional, and (3) gonadal steroid hormone receptors may be restricted to specialized cells of the cardiovasculature.

The effects of both 3,5,3'-triiodo-L-thyronine and spontaneous metamorphosis on Rana catesbeiana liver mRNA were studied using in vitro translation of isolated liver poly(A)+ RNA in a rabbit reticulocyte lysate system. Conventional phenol extraction methods yielded degraded RNA due to high levels of endogenous ribonucleases released upon homogenization of Rana catesbeiana liver. Isolation of intact total RNA was achieved using the potent ribonuclease denaturant, guanidinium thiocyanate. Adult bullfrog serum albumin was purified to homogeneity and a monospecific antibody was elicited against it. A serum protein of 23,000 daltons that migrated near serum albumin on a 6% native gel was also purified to homogeneity. A monospecific antibody was also raised against this protein. Both antibodies were used to quantitatively immunoprecipitate the in vitro translation products of poly(A)+ RNA isolated at intervals following a single injection of triiodothyronine or during various stages of spontaneous amphibian metamorphosis. Triiodothyronine caused a sevenfold increase in translatable albumin mRNA and a threefold increase in translatable mRNA for the 23,000 dalton protein. These increases are consistent with a nuclear initiated mechanism for thyroid hormone action during amphibian metamorphosis.

Ventral prostate S-adenosyl-L-methionine decarboxylase (AMDC) and L-ornithine decarboxylase (ODC) transcript content decreased 5-fold as males aged from 6 to 26 months. In contrast, dorsolateral prostate AMDC and ODC transcript content in these individuals was age invariant. The differential effect of aging on tissue transcript levels reflected respective 3.5- and 5-fold decreases in ventral prostate total and poly(A)+ RNA content in aging males, whereas dorsolateral prostate RNA levels essentially were age invariant. Testosterone injection of 26-month-old males increased ventral and dorsolateral prostate content of AMDC and ODC transcripts 4- and 2.5-fold, respectively. Changes in ventral prostate ODC transcript levels correlated well with previously reported age- and testosterone-mediated changes in prostate ODC protein content; however, the relation between ventral or dorsolateral prostate AMDC mRNA levels and previously determined AMDC protein content was less stringent. Our observation that ventral prostate ODC transcript content was 7-fold greater than that of dorsolateral prostate was insufficient to account for the established 200-fold difference in ODC activity in these tissues. Our data imply that transcript content is a principal determinant of ventral prostate ODC activity in aging AXC/SSh rats. However, this relationship does not appear to characterize either ventral or dorsolateral prostate AMDC activity or relative ventral and dorsolateral prostate ODC activity and transcript content. The cause of the age-related preferential loss of ventral prostate RNA remains to be evaluated.

Immunotitration of L-ornithine decarboxylase (ODC) activity in ventral prostates of young mature (6-month-old) and aged (26-month-old) AXC/SSh rats established that the relation between enzyme activity and prostate ODC mass content was age invariant, demonstrating that the 4-fold diminution in prostate ODC activity in aged subjects represents decreased ODC protein content. Testosterone treatment of aged rats increased prostate ODC activity 2-fold and did not affect prostate ODC half-life. These latter findings and the preceding observation established that the testosterone-mediated increase in prostate ODC activity in aged individuals reflected increased ODC mass content. The half-life of prostate S-adenosyl-L-methionine decarboxylase, another prominent enzyme of polyamine biosynthesis, also was not altered by testosterone treatment of 26-month-old animals. The age-related diminution and testosterone-mediated increase in ventral prostate ODC activity occurred in concert with comparable quantitative changes in ventral prostate ODC transcript content. Because plasma testosterone content was age invariant between 3 and 18 months, the age span during which much of the reduction in prostate ODC activity occurs, and then declined by 50% at 26 months, our studies suggest that age-related diminutions in prostate ODC activity and transcript content reflect altered prostate sensitivity to androgen rather than response to diminished plasma testosterone content. Our data imply that age-related alterations in androgen regulation of androgen-responsive genes may be characteristic of the prostate during aging.