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Objective: Rare coexistence of disease or pathology. Background: Hemiballismus is the most severe form of chorea and is a hyperkinetic disorder characterized by involuntary, high-amplitude movements of the ipsilateral arm and leg, due to lesions of the contralateral side of the central nervous system. Ischemic or hemorrhagic strokes and nonketotic hyperglycemia are predominant etiologies of hemiballismus. Case reports highlighting hemiballismus associated with temporal and parietal lobe infarcts have been published, although research of frontal lobe involvement is limited. Case Report: A 78-year-old woman presented to the Emergency Department with sudden-onset left-sided hemiballismus. On examination, she was alert, oriented to self and time, and able to follow commands. Her neurologic examination was notable for left-sided hemiballismus, described by the provider as periodic, uncontrolled, and involving a "flinging" motion of the left upper and lower extremities, sparing the face. She was treated with benzodiazepines in the Emergency Department and administered intravenous levetiracetam. Computed tomography of the head without contrast revealed an old left basal ganglia lacunar infarct. The patient was then admitted to the inpatient service, where magnetic resonance imaging of the brain revealed an acute punctate left superior frontal gyrus cortical infarct. Outpatient electroencephalogram revealed right anterior hemisphere dysfunction. Conclusions: We describe a patient with left-sided sudden onset hemiballismus with an acute infarct of the ipsilateral superior frontal gyrus. This case highlights that brain lesions separate from the basal ganglia can induce hemiballismus, particularly within the frontal lobe, which warrants further research into precentral sulcus functioning and its role in modulating motor activity. [ABSTRACT FROM AUTHOR]

Human trafficking in the hotel industry represents a hidden threat that demands decisive action. Despite public commitments, the sector's initiatives remain inconsistent, and a wave of lawsuits imposes both financial and reputational risks. Through analysis of relevant legislation and case law, the article demonstrates hotels' potential liability as venues enabling trafficking. However, inconsistent self-regulation and lawsuits reveal limited progress. The authors advocate for insurance companies to play a pivotal role in combatting human trafficking in the hotel industry by strategically adjusting coverage provisions. They trace the historical influence of insurers on the trajectory of slavery when 18th-century British insurers' actions contributed to the rise of abolitionism and argue that similar private regulation today can incentivize hotels' proactive measures against trafficking. The article proposes that insurers possess diverse tools, including exclusions, premium adjustments, auditing, and loss prevention, to compel action rather than complacency. Mandated self-insured retentions can also hold hotels financially accountable for their negligence. However, relying solely on pricing alterations faces challenges due to market competition and inconsistent judicial rulings on liability exclusions. Ultimately, addressing this complex issue requires a collaborative, multi-stakeholder approach. Government fines and prosecutions can further incentivize self-disclosure and cooperation, while publicized settlements can promote transparency and empower consumers to make informed choices for hotel venues. This combined framework can transition hotels from passive enablers to active contributors in the fight against human trafficking, fulfilling their duty of care and catalyzing meaningful progress against human exploitation. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to explore the risk factors that employers consider when assessing an employee's business travel (BT) assignment and the risk treatment, crisis response and recovery strategies they use to discharge their BT duty of care. Design/methodology/approach: An exploratory approach is taken with in-depth interviews of 21 executives, travel managers and insurance brokers involved with the management of BT in four international hotel groups. In all, 12 follow-up interviews were conducted to assess the possible COVID-19 impact on BT risk management processes. Findings: Employers assess BT assignments considering the travel's characteristics, including the destination's risk profile against seven types of risks (health, political, transport, natural, crime, technology and kidnap), length of stay, travel mode and activities undertaken in the destination as well as the traveler's profile which includes diversity and travel experience. Accordingly, they develop a range of duty of care strategies for BT risk treatment, crisis response and recovery. Practical implications: BT practitioners can use the proposed framework to develop risk assessment methodologies based on more accurate destination and traveler profiles and pursue targeted risk treatment strategies and insurance policies. The proposed duty of care approach can be used as a blueprint for organizations to design and manage BT policies. Originality/value: BT risk is an under-researched area. The extant research looks predominantly at travel risks and their assessment taking the traveler's perspective. This study looks at business travel risk and explores it from an employer's risk management perspective offering a BT risk assessment framework and a BT duty of care plan. [ABSTRACT FROM AUTHOR]

The aim of the study was to estimate and to compare effective doses in the elbow region resulting from four different x‐ray imaging modalities. Absorbed organ doses were measured using 11 metal oxide field effect transistor (MOSFET) dosimeters that were placed in a custom‐made anthropomorphic elbow RANDO phantom. Examinations were performed using Shimadzu FH‐21 HR radiography device, Siemens Sensation Open 24‐slice MSCT‐device, NewTom 5G CBCT device, and Planmed Verity CBCT device, and the effective doses were calculated according to ICRP 103 recommendations. The effective dose for the conventional radiographic device was 1.5 µSv. The effective dose for the NewTom 5G CBCT ranged between 2.0 and 6.7 µSv, for the Planmed Verity CBCT device 2.6 µSv and for the Siemens Sensation MSCT device 37.4 µSv. Compared with conventional 2D radiography, this study demonstrated a 1.4–4.6 fold increase in effective dose for CBCT and 25‐fold dose for standard MSCT protocols. When compared with 3D CBCT protocols, the study showed a 6‐19 fold increase in effective dose using a standard MSCT protocol. CBCT devices offer a feasible low‐dose alternative for elbow 3D imaging when compared to MSCT. [ABSTRACT FROM AUTHOR]

The National Commission on Radiation Protection and Measurements has reinforced its recommendation for the use of rectangular collimation for intraoral radiography in its Report No. 177 published in 2019. This study compared effective dose (E) using circular and rectangular collimator (RC) modalities. The authors exposed 18 projections for adult and 12 projections for child full-mouth series using an original equipment 6 centimeter diameter circular collimator (circular), original equipment rectangular positioning indicator device (Focus-RC), and 5 universal RC modalities (JadRad-RC, Rinn-RC, Durr-RC, DEXshield-RC, and TruAlign-RC) for adult and child phantoms. The authors acquired dosimetry using optically stimulated luminescence dosimeters. Exposures were made with a Focus (Instrumentarium) intraoral source using 70 peak kilovoltage and total milliamperes of 5.34 (adult) and 2.7 (child). Adult E was lowest for Focus-RC (54 microsieverts), which also produced the greatest exposure area reduction (51%) compared with circular, followed by JadRad-RC (55 μSv), Durr-RC (58 μSv), Rinn-RC (62 μSv), DEXshield-RC (70 μSv), TruAlign-RC (85 μSv), and circular (86 μSv). Child E followed a similar trend: Focus-RC (44 μSv), JadRad-RC (44 μSv), Durr-RC (45 μSv), Rinn-RC (48 μSv), DEXshield-RC (53 μSv), TruAlign-RC (85 μSv), and circular (89 μSv). When used with thyroid shielding, circular collimation thyroid dose was reduced by as much as 59%. Focus-RC techniques yielded the greatest dose reduction compared with alternative RC and circular. In addition to shape, collimator dimensions should be considered as significant factors affecting patient E. RC alone yielded a greater reduction in thyroid dose than did circular with thyroid shielding. This study's findings underscore the updated recommendations of the National Commission on Radiation Protection and Measurements Report No.177, which emphasized the benefits and important practical considerations of RC with intraoral imaging. [ABSTRACT FROM AUTHOR]

Purpose: Radiation dose is a general concern in diagnostic imaging and a special concern for children who are at greater risk from radiation effects. This study evaluates effective doses (E) produced during 2D and volume imaging with a novel cone beam computed tomography (CBCT) based extremity imaging device. The device's compact size and protocol options offer image choices that enhance the potential for reduced dose and improved diagnostics when evaluating sports injuries. Methods: Hand‐wrist, foot‐ankle, and knee phantoms were developed for use with optically stimulated luminescent dosimeters (OSL). Dosimetry of transmission radiographs (2D) and CBCT volumes (3D) was assessed for Standard and lowered dose (Lite) exposure protocols. Effective dose was calculated for child and adult age groups. Image quality was assessed with contrast‐to‐noise ratio (CNR) and modulation transfer function (MTF). A figure of merit was calculated as the square of CNR divided by E. Results: Standard 2D doses ranged from 0.001–0.06 μSv for adults, 0.001–0.05 μSv for 15‐yr olds, 0.003–0.13 μSv for 10‐yr olds, and 0.005–0.20 for 5‐yr olds. Dose reductions with Lite protocols ranged from 26 to 51%. Standard CBCT doses ranged from 0.3–4.6 μSv for adults, 0.3–4.4 μSv for 15‐yr olds, 0.6–9.8 μSv for 10‐yr olds, and 1–22.6 μSv for 5‐yr olds. For both 2D and 3D a trend of increasing imaging dose with reduced age was present and was statistically significant for children below the age of 10 (P = 0.0009). Lite dose reductions averaged 47%. CNR was statistically reduced in Lite dose scans (P = 0.0384) but was not statistically different using FOM analysis (P = 0.3089). MTF was not significantly affected by the two dose protocols (P = 0.8104). Conclusion: CBCT effective doses calculated from anthropomorphic phantom exposures following manufacturer suggested protocols appear to be substantially less than previously reported doses for similar MDCT extremity examinations. In this study, effective dose from 2D radiographic imaging was approximately two orders of magnitude less than CBCT imaging. Doses were on the order of a few minutes to hours of ubiquitous per‐capita background dose for 2D imaging and a few hours to days for 3D imaging. Dose significantly increased for children younger than age 10. Lite protocols resulted in substantial dose reductions and can be recommended for children and those examinations where reduced CNR will not affect diagnosis. Flexibility of 2D and 3D imaging options with low‐dose protocols make this technology a promising option for radiographic evaluation of the extremities. Efficacy studies are needed to determine when MDCT, CBCT or Digital Radiography are best used for particular diagnostic tasks. [ABSTRACT FROM AUTHOR]

Potency is a critical quality attribute of biological products, defined by the US FDA as the specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result. Ideally, a potency assay will leverage the product's mechanism of action. Alternatively, the assay may focus on a therapeutically relevant biological activity. The absence of rigorous mechanistic data for the majority of cell-based therapeutics currently in the process research pipeline has impeded efforts to design and validate indices of product potency. Development of a systematic battery of parallel functional assays that, taken together, can address all potential mechanisms of action believed to be relevant for the product platform is recommended. Such an approach is especially important during preclinical development. Here, we summarize the principal and unique challenges facing the development of functionally relevant and rigorous potency assays for cell-based therapeutics. We present perspectives regarding potency assay development for these products as illustrated by our experiences in process R&D of cryopreserved hepatocytes (Incara Pharmaceuticals) and selected renal cells (Tengion). [ABSTRACT FROM AUTHOR]

Objective To evaluate the type and prevalence of incidental findings from cone beam computed tomography ( CBCT) of the maxillofacial region. Findings are divided into those that require (i) intervention/referral, (ii) monitoring, and (iii) no further evaluation. Methods Three hundred consecutive CBCT scans conducted in the University of North Carolina School of Dentistry Oral and Maxillofacial Radiology Clinic from January 1 to August 31, 2008 were retrospectively reviewed. Findings were categorized into airway, soft tissue calcifications, bone, temporomandibular joint ( TMJ), endodontic, dental developmental, and pathological findings. Results A total of 272 scans revealed 881 incidental findings (3.2 findings/scan). The most prevalent was airway findings (35%) followed by soft tissue calcifications (20%), bone (17.5%), TMJ (15.4%), endodontic (11.3%), dental developmental (0.7%), and pathological (0.1%). 16.1% required intervention/referral, 15.6% required monitoring, and the remainder (68.3%) required neither. Conclusion This study underscores the need to thoroughly examine all CBCT volumes for clinically significant findings within and beyond the region of interest. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study is to explore the relationship between child pedestrian injuries and socioeconomic characteristics of neighborhoods in the context of local traffic volume. Methods: Child pedestrian collisions were identified in the data of the California Statewide Integrated Traffic Records System (SWITRS). Nine hundred sixty crashes over a 5-year period were identified, geocoded, and mapped to Orange County census tracts. Census data from 2000 were used to identify tracts, population, and population characteristics in the county of approximately 3,000,000 individuals. Pedestrian collision maps were merged with census characteristics and analyzed using STATA (Version 10.1, Stata Corp, College Station, IX) to determine correlations between socioeconomic factors and collision rates within census tracts. Results: The percentage of the population living in households with low income (less than 185% of the federal poverty level) was the strongest predictor of pedestrian injuries. One fourth of census tracts had less than 9 percent of residents with low income and averaged 6 per 100,000 child pedestrian crashes annually. One fourth of the census tracts had more than 32 percent of residents with low income and an average of 56 child pedestrian crashes per 100,000 annually. These data indicate an 8.8-fold increase in collision frequency in the lowest income quartile over the highest income quartile. Other socioeconomic correlates strongly associated with increased child collisions include population density, proportion of population speaking English less than very well, lack of high school education, number of multifamily residences, and Latino ethnicity. Conclusions: Our study showed that child pedestrian collisions are nearly 9 times more frequent in the poorest quartile of neighborhoods than in the richest quartile. Other factors associated with increased pediatric collision risk include increased neighborhood crowding, low levels of education and English speaking ability, and Latino ethnicity. [ABSTRACT FROM AUTHOR]

Myocardin (MYOCD) is a smooth and cardiac muscle-specific transcriptional coactivator that is required for the proper expression of contraction-related genes. Through its function to transactivate effector genes, MYOCD plays an essential role in mediating the switch between contractile and non-contractile phenotypes, particularly in smooth muscle cells (SMC). There are at least two known transcript variants of MYOCD that are expressed in SMC, differing only by the presence (+) or absence (Δ) of Exon 11. To date, no functional role has been assigned to the domain encoded by Exon 11, nor have any notable differences between the ability of each isoform to activate contraction-related genes been observed. In this study we compared sequences for Exon 11 among several mammalian species and identified a highly conserved, putative target sequence for glycogen synthase kinase 3 (GSK3) phosphorylation, suggesting a regulatory role for Exon 11 that can be modulated by alternative splicing. The function of Exon 11 was investigated by altering MYOCD splice selection in cultured porcine SMC with small interfering RNAs (siRNA) and specific chemical inhibitors, resulting in a relative increase in expression of ΔExon 11 variants in the endogenous pool of MYOCD mRNA. The relative increase in ΔExon 11 mRNAs correlated with a reduction of contractile phenotype in the porcine SMC as evidenced by morphological assessment and molecular analysis of effector genes. Together, these data suggest that MYOCD ΔExon 11 may participate in modulating SMC phenotype, potentially acting as a dominant-negative repressor of contraction-related genes. J. Cell. Physiol. 226: 2702-2711, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The availability of suitable human livers for transplantation falls short of the number of potential patients. In addition, the availability of primary human hepatocytes for cell-therapy and drug development applications is significantly limited; less than 700 livers per year are available for such studies. However, the majority of these organs cannot be utilized due to pathological infections (e.g., HepB, HepC, or HIV) or excessive levels of steatosis. Thus, the number of cells needed for cell therapy applications far exceeds the number of cells available from donated livers. The ability to implant progenitor cell populations that can form liver tissue in situ, or can be differentiated in vitro would be a major advance in current cell-based therapies. In addition, and importantly for this application, the ability to utilize a non-hepatic progenitor cell to mimic hepatocytes in vitro would enable the scale-up production of cells for bioartifical liver assist devices, cell-therapy and drug discovery applications. We demonstrate the feasibility of inducing adipose-derived stromal (ASC) cells to express several features of human hepatocytes such as glycogen storage and expression of liver specific genes. Importantly, we also show that undifferentiated ASCs and ASC-derived hepatic cells engraft robustly into the liver in a mouse model of toxic injury. These data indicate a significant potential for the use of undifferentiated ASCs and ASC-derived hepatic cells as novel and valuable products for cell therapy. J. Cell. Physiol. 225: 429–436, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study is to explore the relationship between pedestrian injuries and socioeconomic characteristics. Methods: Pedestrian collisions were identified in the data of the California Statewide Integrated Traffic Records System (SWITRS), which is assembled from police crash reports by the California Highway Patrol Information Services Unit. Four thousand crashes were identified and geocoded within the census tracts in a county population of 2,846,289 over a 5-year period. Population and population characteristics for census tracts were obtained from the 2000 U.S. Census. Results: The percentage of the population living in households with low income (less than 185% of the federal poverty level) was the strongest predictor of pedestrian injuries. One fourth of census tracts had less than 8.7 percent of residents with low income and averaged 11 per 100,000 pedestrian crashes annually. One fourth of the census tracts had more than 32.2 percent of residents with low income and an average of 44 pedestrian crashes per 100,000 annually. Negative binomial regression showed that with each 1 percent increase in the percentage of residents with low income was associated with a 2.8 percent increase in pedestrian crashes. The percentage of residents age 14 years or less, adult residents who had not completed high school, residents who spoke English less than 'very well' and spoke another language at home, and the population density were each associated with a higher frequency of pedestrian crashes. However, when low income was added to these 4 regression models, the relationship between low income and pedestrian crashes increased. Conclusions: Our study showed that pedestrian crashes are 4 times more frequent in poor neighborhoods and that neither age of the population, education, English language fluency, nor population density explained the effect of poverty. [ABSTRACT FROM AUTHOR]

Aims: To comparatively evaluate bladder regeneration following 80% cystectomy and augmentation using a synthetic biopolymer with autologous urothelial and smooth muscle cells (autologous neo-bladder augmentation construct [construct]) or autotransplantation of native bladder (reimplanted native urinary bladder [reimplant]) in canines. Materials & methods: Voiding function, urodynamic assessment and neo-organ capacity-to-body-weight ratio (C:BW) were assessed longitudinally for a total of 24 months following trigone-sparing augmentation cystoplasty in juvenile canines. Results: Within 30 days postimplantation, hematology and urinalysis returned to baseline. Constructs and reimplants yielded neo-organs with statistically equivalent urodynamics and histology. Linear regression analysis of C:BW showed that constructs regained baseline slope and continued to adapt with animal growth. Conclusions: Constructs and reimplants regained and maintained native bladder histology by 3 months, capacity at 3-6 months and compliance by 12-24 months. Furthermore, construct C:BW demonstrated the ability of regenerated bladder to respond to growth regulation. [ABSTRACT FROM AUTHOR]

Objective: To compare measurements from synthesized cone-beam computed tomography (CBCT) lateral cephalograms using orthogonal and perspective projections with those from conventional cephalometric radiographs. Materials and Methods: Thirty-one patients were imaged using CBCT and conventional cephalometry. CBCT volume data were imported in Dolphin 3D. Orthogonal and perspective lateral cephalometric radiographs were created from three-dimensional (3D) virtual models. Twelve linear and five angular measurements were made on synthesized and conventional cephalograms in a randomized fashion. Conventional image measurements were corrected for known magnification. Linear and angular measurements were compared between image modalities using repeated measures analysis of variance. Statistical significance was defined as an α level of .01. Results: With the exception of the Frankfort-mandibular plane angle (P < .0001), angular measurements were not statistically different for any modality (P > .01). Linear measurements, whether based on soft or hard tissue landmarks, were not statistically different (P > .01). Conclusions: Measurements from in vivo CBCT synthesized cephalograms are similar to those based on conventional radiographic images. Thus, additional conventional imaging may generally be avoided when CBCT scans are acquired for orthodontic diagnosis. [ABSTRACT FROM AUTHOR]

Adipose tissue serves as a source of adipokines and cytokines with both local and systemic actions in health and disease. In this study, we examine the hypothesis that multipotent human adipose-derived stem cells (ASCs), capable of differentiating along the adipocyte, chondrocyte, and osteoblast pathways, contribute to adipose tissue-derived cytokine secretion. Following exposure to basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF), the ASCs significantly increase their secretion of hepatocyte growth factor (HGF), a cytokine implicated in hematopoiesis, vasculogenesis, and mammary epithelial duct formation. Ascorbic acid synergizes with these inductive factors, further increasing HGF levels. Following exposure to lipopolysaccharide, ASCs increase their secretion of both hematopoietic (granulocyte/monocyte, granulocyte, and macrophage colony stimulating factors, interleukin 7) and proinflammatory (interleukins 6, 8, and 11, tumor necrosis factor α) cytokines based on ELISA and RT-PCR. In co-cultures established with umbilical cord blood-derived CD34+ cells, the ASCs support long-term hematopoiesis in vitro. Furthermore, in short-term 12-day co-cultures, the ASC maintain and expand the numbers of both myeloid and lymphoid progenitors. These observations are consistent with the functionality of the secreted cytokines and confirm recent reports by other laboratories concerning the hematopoietic supportive capability of ASCs. We conclude that the ASCs display cytokine secretory properties similar to those reported for bone marrow-derived mesenchymal stem cells (MSCs). J. Cell. Physiol. 212:702–709, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Hedgehog signaling through its receptor, Patched, activates transcription of genes, including Patched, that regulate the fate of various progenitors. Although Hedgehog signaling is required for endodermal commitment and hepatogenesis, the possibility that it regulates liver turnover in adults had not been considered because mature liver epithelial cells lack Hedgehog signaling. Herein, we show that this pathway is essential throughout life for maintaining hepatic progenitors. Patched-expressing cells have been identified among endodermally lineage-restricted, murine embryonic stem cells as well as in livers of fetal and adult Ptc-lacZ mice. An adult-derived, murine hepatic progenitor cell line expresses Patched, and Hedgehog-responsive cells exist in stem cell compartments of fetal and adult human livers. In both species, manipulation of Hedgehog activity influences hepatic progenitor cell survival. Therefore, Hedgehog signaling is conserved in hepatic progenitors from fetal development through adulthood and may be a new therapeutic target in patients with liver damage. [ABSTRACT FROM AUTHOR]

Background: The product of the retinoblastoma-susceptibility gene (pRb) is a substrate for Protein Phosphatase 1 (PP1). At mitotic exit, all three PP1 isoforms, α, γ1 and δ, bind to pRb and dephosphorylate its Ser/Thr sites in a sequential and site-specific way. The pRb-C terminal has been reported to be necessary and sufficient for PP1α binding. The present study investigated whether the three PP1 isoforms from mitotic or asynchronous HeLa cells associate differentially with wildtype and pRb mutants, as well as the holoenzyme composition of the pRb-directed PP1. Results: The requirement for the entire pRb molecule to achieve optimal PP1-binding was indicated by the fact that full-length pRb displayed the highest affinity for all three PP1 isoforms. Ser/Thr-to-Ala substitution for up to 14 pRb sites did not affect the ability of pRb to bind the PP1 isoforms derived from mitotic or asynchronous HeLa cells, thus suggesting that the phosphateaccepting residues on pRb do not regulate the interaction with PP1. To probe for the presence of PP1 targeting subunits in the pRb-directed PP1 complex, PP1 from mitotic or asynchronous HeLa cells was isolated by affinity chromatography on GST-Rb (either full-length or its deletion mutants Rb-big pocket or Rb-C-terminal). The PP1 was always obtained as free catalytic subunit, displaying all three isoforms, thus suggesting direct interaction between pRb and PP1. The direct association was confirmed by the ability of pRb to pull-down purified PP1 catalytic subunits and by in vitro reconstitution of a complex between PP1 catalytic subunit and the pRb-C-terminal. Conclusion: The work indicated that the full length of the pRb molecule is required for optimal interaction with the PP1 isoforms and that the association between pRb and PP1 isoforms is direct. [ABSTRACT FROM AUTHOR]

Cho J-J, Joseph B, Sappal BS, Giri RK, Wang R, Ludlow JW, Furth ME, Susick R, Gupta S. Analysis of the functional integrity of cryopreserved human liver cells including xenografting in immunodeficient mice to address suitability for clinical applications. Liver International 2004: 24: 361–370. © Blackwell Munksgaard 2004 The availability of well-characterized human liver cell populations that can be frozen and thawed will be critical for cell therapy. We addressed whether human hepatocytes can recover after cryopreservation and engraft in immunodeficient mice. We isolated cells from discarded human livers and studied the properties of cryopreserved cells. The viability of thawed cells was established with multiple in vitro assays, including analysis of liver gene expression, ureagenesis, cytochrome P450 activity, and growth factor-induced cell proliferation. The fate of transplanted cells was analysed in immunodeficient NOD-SCID mice. After thawing, the viability of human hepatocytes exceeded 60%. Cells attached to culture dishes, proliferated following growth factor stimulation and exhibited liver-specific functions. After transplantation in NOD-SCID mice, cells engrafted in the peritoneal cavity, a heterologous site, as well as the liver itself, retained hepatic function and proliferated in response to liver injury. Transplanted hepatocytes were integrated in the liver parenchyma. Occasionally, transplanted cells were integrated in bile ducts. Cryopreserved human liver cell showed the ability to retain functional integrity and to reconstitute both hepatic and biliary lineages in mice. These studies offer suitable paradigms aimed at characterizing liver cells prior to transplantation in people. [ABSTRACT FROM AUTHOR]

Background : One of the major cellular serine/threonine protein phosphatases is protein phosphatase type 1 (PP1). Studies employing many eukaryotic systems all point to a crucial role for PP1 activity in controlling cell cycle progression. One physiological substrate for PP1 appears to be the product of the retinoblastoma susceptibility gene (pRB), a demonstrated tumor suppressor. The growth suppressive activity of pRB is regulated by its phosphorylation state. Of critical importance is the question of the in vivo effect of PP1 activity on pRB and growth regulation. As a first step towards addressing this question, we developed an inducible PP1 expression system to investigate the regulation of PP1 activity. Results : We have established a cell line for inducing protein expression of the type 1, alpha-isotype, serine/threonine protein phosphatase (PP1α). A plasmid encoding a fusion protein of the catalytic subunit of PP1α with a 6-histidine peptide (6His) and a peptide from hemagluttinin (HA) was transfected into the UMUC3 transitional cell carcinoma cell line, previously transfected with the reverse tetracycline transactivator plasmid pUHD172-1neo. A stable cell line designated LLWO2F was established by selection with hygromycin B. 6His-HA-PP1α protein appeared in cell lysates within two hours following addition of doxycycline to the culture medium. This protein localizes to the nucleus as does endogenous PPIα, and was shown to associate with PNUTS, a PPI- nuclear targeting subunit. Like endogenous PPIα, immunocomplexed 6His-HA-PP1α is active toward phosphorylase a and the product of the retinoblastoma susceptibility gene, pRB. When forcibly overexpressing 6His-HA-PPIα, there is a concomitant decrease in endogenous PPIα levels. Conclusions : These data suggest the existence of an autoregulatory mechanism by which PPIα protein levels and activity remain relatively constant. RT-PCR analyses of isolated polysome fractions support the notion that this putative autoregulatory mechanism is exerted, at least in part, at the translational level. Implications of these findings for the study of PPIα function in vivo are discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine if there was a significant difference in the diagnostic quality of the initial full-mouth series (FMS) exposed by first-year dental students after viewing a Computer Assisted Instruction (CAI) module on radiographic technique as compared to those who did not and to determine if students who used the CAI module expressed a preference to using it and would recommend its use prior to exposure. Fifty-nine first-year dental students were randomly selected and assigned to two groups (students who did not view a CAI CD and students who did) before exposing their initial FMS on a Dental X-ray Training and Teaching Replica (DXTTR). For each radiographic series, a radiology faculty member determined the total number of error points based on performance criteria. The Wilcoxon Rank Sum Test was used to determine significance between the two groups, p = .05. After exposing the FMS, students in the second group completed a questionnaire to assess their preference for using the CAI CD. The Sign Rank Test was used to determine preference, p = .05. No significant difference in error points were found to exist between the two groups. Dental students who reviewed the CAI preferred using it and would recommend it to others before exposing their FMS. [ABSTRACT FROM AUTHOR]

Analysis of the viability, differentiation, clonogenicity and function of human stem/progenitor cells requires suitable xenograft models. However, the identification of transplanted cells has been generally difficult. Fluorescence in situ hybridization is a tedious method for analyzing tissues, and localization of transplanted cells with X or Y chromosome probes is limited by the sparse signals produced. Therefore, we examined the possibility of generating either pan-nuclear signals with a total human DNA probe or multiple nuclear signals with a pan-centromeric human DNA probe. The probes were labeled with digoxigenin to make reaction products visible by light microscopy and to allow the use of immunohistochemistry methods incorporating various color schemes to demonstrate specific properties of transplanted cells. The ability to localize all types of nucleated human cells with such probes will facilitate studies of stem cell biology and cell and gene therapy, as well as the development of new animal models. [ABSTRACT FROM AUTHOR]

Tuned Aperture Computed Tomography or TACT® is a relatively new technique that transform correlated two-dimensional images into a three-dimensional display. Associating TACT with digital subtraction radiography (TACT-DSR) may enhance its use in the detection of diseases. This study aims to assess observer performance in the task of detecting simulated bone-gain in periodontal defects, comparing conventional and TACT DSR. Buccal, lingual and proximal pericrestal bony defects in a human and wax mixtures using standardized vertical bitewing projections, acquired with an intraoral digital receptor in a tomographic X-ray machine. One hundred and twenty pairs of baseline and follow-up images were obtained for each imaging modality. Post-acquisition processing including image-registration, density-correction and subtraction operation were applied to both transmission images and TACT-slices. Eight calibrated observers evaluated the presence or a absence of pericrestal bone-gain using a 5-point confidence scale. Details about the location of periodontal defects and the amount of bone-gain for each subtracted image were recorded and used in the statistical analysis. Observer performance and study design factors were analyzed by means of receiver operating characteristic (ROC) curve analysis and ANOVA. Mean values of areas under ROC curves for bone-gain detection performance were 0.82 for conventional DSR and 0.90 for TACT-DSR. TACT-DSR provided statistically superior detection performance of simulated periodontal bone-gain over conventional DSR for both-obscured defects (p=0.001) and for the smallest bone mass (p=0.024). The findings support TACT-DSR's potential to provide greater sensitivity and technique flexibility in detecting periodontal bone-gain than standard DSR. [ABSTRACT FROM AUTHOR]

pRb is dephosphorylated at mitotic exit by the type 1 serine/threonine protein phosphatases (PP1). Here we demonstrate for the first time that mitotic pRb dephosphorylation is a sequential, temporally-regulated event. We also provide evidence that the three mammalian isoforms of PP1, α, γ-1, and δ, differ in their respective preferences for site-specific pRb dephosphorylation and that the mitotic and G1 PP1-isoform counterparts exhibit differential activities towards mitotic pRb. Finally, the physiological relevance of the striking contrast between the patterns of Thr821 and Thr826 dephosphorylation, sites known to be important for disrupting binding of LXCXE-containing proteins to pRb, is addressed. Oncogene (2001) 20, 3776–3785. [ABSTRACT FROM AUTHOR]

The retinoblastoma gene product (pRb) interacts with many cellular proteins to function in the control of cell division, differentiation, and apoptosis. Several pRb binding proteins complex with pRb through an amino acid sequence called the LXCXE motif. The catalytic subunit of DNA polymerase δ (p125) contains a LXCXE motif. To further study the biochemical function of this polymerase, we sought to determine if p125 interacts with pRb. Experiments using GST-pRb fusion proteins showed that p125 from breast epithelial (MCF10A) cell extracts associates with pRb. In addition, GST-p125 fusion proteins bound pRb from the same cell extracts. The pRb that associated with GST-p125 was largely unphosphorylated. Coimmunoprecipitation experiments using cell cycle synchronized cells revealed that p125 and pRb form a complex predominantly during G1 phase, the phase during which pRb is mostly unphosphorylated. In vitro phosphorylation of GST-pRb by the cyclin dependent kinases reduced the ability of p125 to associate with GST-pRb. Addition of the LXCXE containing protein SV40 large T antigen to GST-pRb blocks the ability of p125 to associate with pRb, suggesting that it may be through a LXCXE sequence by which p125 interacts with pRb. Finally, in vitro polymerase assays demonstrate that GST-pRb fusion protein stimulates DNA polymerase δ activity. Oncogene (2000) 19, 5464–5470. [ABSTRACT FROM AUTHOR]

Self-guided slide/tape (ST) and web page (WP) instruction in normal radiographic anatomy of periapical and panoramic images is compared using objective test performance and subjective preference of freshman dental students. A class of seventy-four students was divided into a group studying anatomy in periapical images using WP and a group studying similar ST material. In a modified cross-over design the groups switched presentation technologies to learn anatomy in panoramic images. Students completed self-administered on-line quizzes covering WP materials and conventional quizzes for ST material. Students also completed a voluntary survey. Mean quiz performance identifying matched anatomic features in PA (n = 26) and panoramic images (n = 35) was excellent (96.9%) and not different between image types (p = 0.12) or presentation technologies (p = 0.81). Students preferred WP for accessibility, ease of use, freedom of navigation, and image quality (p < .01). Student comfort level with the quiz formats of the two technologies was not different (p = 0.11). Students experienced a higher rate of mechanical and logistical problems with ST than with WP technology. While 71 percent of the students preferred WP technology, this preference appears to be related to ease of use and facilitation of flexible learning styles rather than improved didactic performance. [ABSTRACT FROM AUTHOR]

The product of the retinoblastoma susceptibility gene, pRB, is a demonstrated substrate for the type 1 serine/threonine protein phosphatases (PP1). Curiously, there has been a paucity of data supporting the idea that phosphorylated pRB can be found in a complex with PP1. To more fully characterize the association between these two proteins, we utilized a PP1-affinity chromatography approach to increase our ability to capture from mammalian cell lysate populations of pRB capable of binding to PP1. Western blot analysis of the bound proteins indicates that both faster migrating, hypophosphorylated pRB, as well as slower migrating, hyperphosphorylated pRB can bind. Phosphorylated pRB binding was confirmed by immunoprecipitation of eluted 32P-labeled pRB. In addition, Western blotting of eluted proteins with pRB phosphorylated-site-specific antibodies revealed select phosphorylated forms of pRB binding to PP1. Similar binding studies performed with toxin-inhibited PP1 indicate that catalytic activity of PP1 is not required for pRB binding. The significance of this finding with respect to the functional importance of this interaction is discussed. [ABSTRACT FROM AUTHOR]

The retinoblastoma protein (Rb) acts as a critical cell-cycle regulator and loss of Rb function is associated with a variety of human cancer types. Here we report that Rb binds to members of the AP-1 family of transcription factors, including c-Jun, and stimulates c-Jun transcriptional activity from an AP-1 consensus sequence. The interaction involves the leucine zipper region of c-Jun and the B pocket of Rb as well as a C-terminal domain. We also present evidence that the complexes are found in terminally differentiating keratinocytes and cells entering the G1 phase of the cell cycle after release from serum starvation. The human papillomavirus type 16 E7 protein, which binds to both c-Jun and Rb, inhibits the ability of Rb to activate c-Jun. The results provide evidence of a role for Rb as a transcriptional activator in early G1 and as a potential modulator of c-Jun expression during keratinocyte differentiation. [ABSTRACT FROM AUTHOR]

Exposure of CV-1P cells to hypoxic conditions results in reversible cell cycle arrest concomitant with accumulation of pRB in the hypophosphorylated, growth suppressive form. Similar to cell cycle arrest induced by serum starvation, we show here that hypoxia-induced arrest is accompanied by a decrease in pRB-directed CDK4 and CDK2 activities, lower cyclin D and E protein levels, and by an increase in p27 protein abundance. Immunoprecipitation studies reveal an increase in p27 association with cyclin E-CDK2 complexes. In contrast to cell cycle arrest induced by serum starvation, hypoxia increases PP1-mediated pRB dephos-phorylation. These data reveal that synergy between decreased pRB-directed cyclin/CDK activity and increased pRB-directed phosphatase activity contribute towards inducing and maintaining pRB in its hypophos-phorylated, growth suppressive state during hypoxia. [ABSTRACT FROM AUTHOR]

We have previously reported on the M-phase specific dephosphorylation of pRb and identified a type 1 serine/threonine protein phosphatase (PP1) as the enzyme mediating pRb dephosphorylation. In this report, we have characterized the pRb-directed phosphatase activity found in mitotic cells with respect to dose dependence and demonstrate that the pRb isoform conversion detected in vitro mirrors the pRb isoform conversion which occurs during mitosis of intact cells. Cell fractionation and PP1 catalytic subunit isolation studies support the notion that the pRb-directed phosphatase activity involves subpopulations of PP1 catalytic subunits. Coprecipitation studies revealed that PP1 can form a complex with hypophosphorylated pRb which was converted from the hyperphosphorylated form in mitotic cell extracts. Taken together with data from previous reports in the literature, a model for the regulation of PP1 activity towards pRb during mitotic exit is proposed. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about antepartum dental radiography and low birth weight.

Presents a letter to the editor regarding the resolution of digitized intraoral dental films.