bluuebunny/crossref_metadata_2025 huggingface dataset:
Communicating With the Public About Emerging Health Threats: Lessons From the Pre-Event Message Development Project
Authors: Wray Ricardo J. , Becker Steven M. , Henderson Neil , Glik Deborah , Jupka Keri , Middleton Sarah , Henderson Carson , Drury Allison , Mitchell Elizabeth W.
Published: April 2008

Objectives. We sought to better understand the challenges of communicating with the public about emerging health threats, particularly threats involving toxic chemicals, biological agents, and radioactive materials.

Methods. At the request of the Centers for Disease Control and Prevention, we formed an interdisciplinary consortium of investigative teams from 4 schools of public health. Over 2 years, the investigative teams conducted 79 focus group interviews with 884 participants and individual cognitive response interviews with 129 respondents, for a total sample of 1013 individuals. The investigative teams systematically compared their results with other published research in public health, risk communication, and emergency preparedness.

Results. We found limited public understanding of emerging biological, chemical, and radioactive materials threats and of the differences between them; demand for concrete, accurate, and consistent information about actions needed for protection of self and family; active information seeking from media, local authorities, and selected national sources; and areas in which current emergency messaging can be improved.

Conclusions. The public will respond to a threat situation by seeking protective information and taking self-protective action, underlining the critical role of effective communication in public health emergencies.
Effects of Enrollment in Medicaid Versus the State Children’s Health Insurance Program on Kindergarten Children’s Untreated Dental Caries
Authors: Brickhouse Tegwyn H. , Rozier R. Gary , Slade Gary D.
Published: April 2008

Objectives. We compared levels of untreated dental caries in children enrolled in public insurance programs with those in nonenrolled children to determine the impact of public dental insurance and the type of plan (Medicaid vs State Children’s Health Insurance Program [SCHIP]) on untreated dental caries in children.

Methods. Dental health outcomes were obtained through a calibrated oral screening of kindergarten children (enrolled in the 2000–2001 school year). We obtained eligibility and claims data for children enrolled in Medicaid and SCHIP who were eligible for dental services during 1999 to 2000. We developed logistic regression models to compare children’s likelihood and extent of untreated dental caries according to enrollment.

Results. Children enrolled in Medicaid or SCHIP were 1.7 times (95% confidence interval [CI] = 1.65, 1.77) more likely to have untreated dental caries than were nonenrolled children. SCHIP-enrolled children were significantly less likely to have untreated dental caries than were Medicaid-enrolled children (odds ratio [OR]=0.74; 95% CI=0.67, 0.82). According to a 2-part regression model, children enrolled in Medicaid or SCHIP have 17% more untreated dental caries than do nonenrolled children, whereas those in SCHIP had 16% fewer untreated dental caries than did those in Medicaid.

Conclusions. Untreated tooth decay continues to be a significant problem for children with public insurance coverage. Children who participated in a separate SCHIP program had fewer untreated dental caries than did children enrolled in Medicaid.
Bioterrorism Surveillance and Privacy: Intersection of HIPAA, the Common Rule, and Public Health Law
Authors: Nordin James D. , Kasimow Sophie , Levitt Mary Jeanne , Goodman Michael J.
Published: April 2008

The threat of bioterrorism in the wake of the September 11, 2001, terrorist attacks cannot be ignored. Syndromic surveillance, the practice of electronically monitoring and reporting real-time medical data to proactively identify unusual disease patterns, highlights the conflict between safeguarding public health while protecting individual privacy.

Both the Health Insurance Portability and Accountability Act and the Common Rule (which promulgates protections for individuals in federally sponsored medical research programs) safeguard individuals. Public health law protects the entire populace; uneven state-level implementation lacks adequate privacy protections.

We propose 3 models for a nationwide bioterrorism surveillance review process: a nationally coordinated systems approach to using protected health information, creating public health information privacy boards, expanding institutional review boards, or some combination of these.
A Randomized Intervention Trial to Reduce the Lending of Used Injection Equipment Among Injection Drug Users Infected With Hepatitis C
Authors: Latka Mary H. , Hagan Holly , Kapadia Farzana , Golub Elizabeth T. , Bonner Sebastian , Campbell Jennifer V. , Coady Micaela H. , Garfein Richard S. , Pu Minya , Thomas Dave L. , Thiel Thelma K. , Strathdee Steffanie A.
Published: April 2008

Objectives. We evaluated the efficacy of a peer-mentoring behavioral intervention designed to reduce risky distributive injection practices (e.g., syringe lending, unsafe drug preparation) among injection drug users with hepatitis C virus (HCV) infection.

Methods. A randomized trial with a time-equivalent attention-control group was conducted among 418 HCV-positive injection drug users aged 18 to 35 years in 3 US cities. Participants reported their injection-related behaviors at baseline and at 3- and 6-month follow-ups.

Results. Compared with the control group, intervention-group participants were less likely to report distributive risk behaviors at 3 months (odds ratio [OR]=0.46; 95% confidence interval [CI]=0.27, 0.79) and 6 months (OR=0.51; 95% CI=0.31, 0.83), a 26% relative risk reduction, but were no more likely to cite their HCV-positive status as a reason for refraining from syringe lending. Effects were strongest among intervention-group participants who had known their HCV-positive status for at least 6 months. Peer mentoring and self-efficacy were significantly increased among intervention-group participants, and intervention effects were mediated through improved self-efficacy.

Conclusions. This behavioral intervention reduced unsafe injection practices that may propagate HCV among injection drug users.
The Relationship Between In-Home Water Service and the Risk of Respiratory Tract, Skin, and Gastrointestinal Tract Infections Among Rural Alaska Natives
Authors: Hennessy Thomas W. , Ritter Troy , Holman Robert C. , Bruden Dana L. , Yorita Krista L. , Bulkow Lisa , Cheek James E. , Singleton Rosalyn J. , Smith Jeff
Published: April 2008

Objectives. We investigated the relationship between the presence of in-home piped water and wastewater services and hospitalization rates for respiratory tract, skin, and gastrointestinal tract infections in rural Alaska.

Methods. We determined in-home water service and hospitalizations for selected infectious diseases among Alaska Natives by region during 2000 to 2004. Within 1 region, infant respiratory hospitalizations and skin infections for all ages were compared by village-level water services.

Results. Regions with a lower proportion of home water service had significantly higher hospitalization rates for pneumonia and influenza (rate ratio [RR] = 2.5), skin or soft tissue infection (RR = 1.9), and respiratory syncytial virus (RR = 3.4 among those younger than 5 years) than did higher-service regions. Within 1 region, infants from villages with less than 10% of homes served had higher hospitalization rates for pneumonia (RR = 1.3) and respiratory syncytial virus (RR = 1.2) than did infants from villages with more than 80% served. Outpatient Staphylococcus aureus infections (RR = 5.1, all ages) and skin infection hospitalizations (RR = 2.7, all ages) were higher in low-service than in high-service villages.

Conclusions. Higher respiratory and skin infection rates were associated with a lack of in-home water service. This disparity should be addressed through sanitation infrastructure improvements.
States and Substance Abuse Treatment Programs: Funding and Guidelines for Infection-Related Services
Authors: Kritz Steven , Brown Lawrence S. , Goldsmith R. Jeffrey , Bini Edmund J. , Robinson Jim , Alderson Donald , Novo Patricia , Rotrosen John
Published: April 2008

Community-based substance abuse treatment programs provide HIV, hepatitis C virus, and sexually transmitted infection services. To explore how state funding and guidelines affect practice, we surveyed state agency administrators and substance abuse treatment program administrators and clinicians regarding 8 infection-related services. Although state funding for infection-related services is widely available, substance abuse treatment programs do not always access it. Substance abuse treatment program guidelines are clearer in states that have written guidelines. Improved communication between state agencies and substance abuse treatment programs may enhance service.
Population Attributable Fractions of Psychiatric Disorders and Suicide Ideation and Attempts Associated With Adverse Childhood Experiences
Authors: Afifi Tracie O. , Enns Murray W. , Cox Brian J. , Asmundson Gordon J.G. , Stein Murray B. , Sareen Jitender
Published: April 2008

Objectives. We sought to determine the fractions of psychiatric disorders and suicide ideation and attempts in a general population sample attributable to childhood physical abuse, sexual abuse, and witnessing domestic violence.

Methods. Data were obtained from the US National Comorbidity Survey Replication. Population attributable fractions were calculated to determine the proportion of psychiatric disorders and suicide ideation and attempts attributable to adverse childhood experiences. The analysis was stratified by gender.

Results. The estimated attributable fractions for psychiatric disorders attributable to having experienced any adverse childhood event ranged from 22% to 32% among women and 20% to 24% among men. Having experienced any adverse event accounted for a substantial proportion of suicide ideation and attempts among women (16% and 50%, respectively) and men (21% and 33%, respectively). Substantial proportions of poor mental health outcomes were also attributable to increasing number of adverse events.

Conclusions. The estimated proportions of poor mental health outcomes attributed to childhood adversity were medium to large for men and women. Prevention efforts that reduce exposure to adverse childhood events could substantially reduce the prevalence of psychopathology and suicidal behavior in the general population.
Intervening to Reduce Inequalities in Infections in Europe
Authors: Semenza Jan C. , Giesecke Johan
Published: April 2008

The European Centre for Disease Prevention and Control was founded in response to newly emerging infections such as severe acute respiratory syndrome and avian influenza. However, Europe faces other communicable disease challenges that have proven to be remarkably resilient to public health interventions.

We present examples of communicable diseases with inequitable distribution among those with poor educational attainment, low income, or other socioeconomic factors in every European country. Because these findings are incompatible with social justice and fairness, we examine strategic interventions targeting upstream causes of communicable disease transmission keeping in mind 10 indispensable public health functions essential to reach marginalized groups.

These interventions have to be tailored to the socio-political context and rely on community-based decision-making and intersectorial collaboration.
Characteristics of Physically Active Smokers and Implications for Harm Reduction
Authors: deRuiter Wayne K. , Faulkner Guy , Cairney John , Veldhuizen Scott
Published: April 2008

Objectives. We sought to establish the prevalence of physical activity among smokers, whether or not physically active smokers were more likely to attempt cessation, and who these physically active smokers were.

Methods. We used logistic regression to contrast physically active and inactive smokers in a secondary data analysis of the Canadian Community Health Survey Cycle 1.1.

Results. Physically active smokers represented almost one quarter of the smoking population. Compared with physically inactive smokers, physically active smokers were more likely to have attempted cessation in the past year. Physically active smokers were more likely to be young, single, and men compared with their inactive counterparts. Income had no influence in distinguishing physically active and inactive smokers.

Conclusions. Skepticism persists regarding the practicality and potential risks of promoting physical activity as a harm-reduction strategy for tobacco use. We found that a modest proportion of the daily smoking population was physically active and that engagement in this behavior was related to greater cessation attempts. Interventions could be developed that target smokers who are likely to adopt physical activity.
Keeping Guns Out of the Hands of Abusers: Handgun Purchases and Restraining Orders
Authors: Vittes Katherine A. , Sorenson Susan B.
Published: April 2008

Persons under certain domestic violence restraining orders are prohibited by federal law from purchasing and possessing a firearm. We used administrative data from California to link 794426 restraining orders with 1388724 handgun purchase applications. We found that restrained persons were not a less law-abiding group in general, but they appeared to be repeatedly or serially abusive to intimate partners, and their handgun purchase rates were highest after their restraining orders expired.
Exact solutions of the D-dimensional Schrödinger equation for a ring-shaped pseudoharmonic potential
Authors: Ikhdair Sameer , Sever Ramazan
Published: April 2008

A new non-central potential, consisting of a pseudoharmonic potential plus another recently proposed ring-shaped potential, is solved. It has the form $$
V(r,\theta ) = \tfrac{1}
{8}\kappa r_e^2 \left( {\tfrac{r}
{{r_e }} - \tfrac{{r_e }}
{r}} \right)^2 + \tfrac{{\beta cos^2 \theta }}
{{r^2 sin^2 \theta }}
$$. The energy eigenvalues and eigenfunctions of the bound-states for the Schrödinger equation in D-dimensions for this potential are obtained analytically by using the Nikiforov-Uvarov method. The radial and angular parts of the wave functions are obtained in terms of orthogonal Laguerre and Jacobi polynomials. We also find that the energy of the particle and the wave functions reduce to the energy and the wave functions of the bound-states in three dimensions.
On solutions of the Schrödinger equation for some molecular potentials: wave function ansatz
Authors: Ikhdair Sameer , Sever Ramazan
Published: April 2008

Making an ansatz to the wave function, the exact solutions of the D-dimensional radial Schrödinger equation with some molecular potentials, such as pseudoharmonic and modified Kratzer, are obtained. Restrictions on the parameters of the given potential, δ and ν are also given, where η depends on a linear combination of the angular momentum quantum number ℓ and the spatial dimensions D and δ is a parameter in the ansatz to the wave function. On inserting D = 3, we find that the bound state eigensolutions recover their standard analytical forms in literature.
Anti-control of chaos in Bose-Einstein condensates
Authors: Wang Zhixia , Shen Ke
Published: April 2008

The spatial structure of a Bose-Einstein Condensate (BEC) loaded into an optical lattice potential is investigated. We suggest a method for generating chaos in BEC by modulating periodic signals to convert the regular states into chaotic states. The maximal Lyapunov exponent is calculated as a function of modulation intensity and modulation frequency respectively, and the chaotic orbits associated with the positive Lyapunov exponents.
Scanning tunneling spectrosopy study of DNA conductivity
Authors: Kratochvílová Irena , Král Karel , Bunček Martin , Nešpůorek Stanislav , Todorciuc Tatiana , Weiter Martin , Navrátil Jiři , Schneider Bohdan , Pavluch Jiři
Published: April 2008

We used STM to study the conductivity of 32 nucleotide long DNA molecules chemically attached to a gold surface. Two oligonucleotides containing all four base types namely G, A, C, T, one single stranded and one double helical, all showed conductance data significantly higher than DNA containing only T and A that were either single stranded d(T32) or double helical d(T32).d(A32) in confirmation. Within each sequence group, the conductivity of the double helical form was always higher than that of the single strand. We discuss the impact of structure, particular base stacking and affinity to the phase transition.
Treatment questions in POTS with hypertension and syncope
Authors: Lelonek Malgorzata , Goch Jan
Published: April 2008

A 27-year old man experienced recurrent syncope with prodromal palpitations and resultant injury. The features of these episodes suggested a potentially neurally-mediated mechanism. Head-up tilt test revealed the postural orthostatic tachycardia syndrome (POTS). Within the first minutes of upright posture during the total head-up tilt testing, a heart rate increase of >30 beats/min and to a maximum of 150 beats/min was documented in the patient. At the end of passive tilting, the patient lost consciousness in the absence of hypotension while in sinus rhythm of 140 bpm. The 12-lead ECG and electrophysiological study showed no abnormalities. The patient received a beta-adrenergic blocker, a selective central imidazoline receptor agonist and psychiatric therapy, resulting in only a short-term improvement.
Influence of the wars in Croatia and Bosnia and Herzegovina on the incidence and outcome of singleton premature births in the Split University Hospital
Authors: Pavlinac Ivana , Marin Ana , Valić Maja , Marušić Jelena , Roje Damir , Pecotić Renata , Tadin Ivica , Ðogaš Zoran
Published: April 2008

To investigate the influence of the wars in Croatia and Bosnia and Herzegovina on incidence and perinatal outcome of singleton preterm births at the Department of Gynecology and Obstetrics in the Split University Hospital. Data were collected by reviewing patients’ files at the Department of Gynecology and Obstetrics from three periods: the three years before the war (1988–1990), during the war (1992–1994), and after the war (1996–1998). A total of 2,358 patients’ files of singleton preterm delivery were analyzed. Singleton preterm delivery rate decreased during the war (5.02%) and post-war period (4.74%) compared to the pre-war period (6.19%). Stillbirth and early neonatal mortality rates of singleton premature babies significantly increased during the war to 226%, compared to 193% before the war and 134% after the war. Early neonatal mortality rate was 215% during the war, 209% in the pre-war period, and 156% after the war. Despite the continuous decrease in singleton preterm birth rate throughout the observed periods, the increase in stillbirth rate and early neonatal mortality rate during the war might have been caused by the war. This may be due to primary gynecological care being inadequate for many pregnant women.
Kinetic models for stochastically modified ionic channels
Authors: Wozinski Aleksander , Iwaniszewski Jan
Published: April 2008

Ionic channels form pores in biomembranes. These pores are large macromolecular structures. Due to thermal fluctuations of countless degrees-of-freedom of the biomembrane material, the actual form of the pores is permanently subject to modification. Furthermore, the arrival of an ion at the binding site can change this form by repolarizing the surrounding aminoacids. In any case the variations of the pore structure are stochastic. In this paper, we discuss the effect of such modifications on the channel conductivity. Applying a simple kinetic description, we show that stochastic variations in channel properties can significantly alter the ionic current, even leading to its substantial increase or decrease for the specific matching of some time-scales of the system.
Hepatocyte Transplantation in the Treatment of Acute Liver Failure: Microencapsulated Hepatocytes versus Hepatocytes Attached to an Autologous Biomatrix
Authors: Ambrosino Giovanni , Varotto Sergio , Basso Stefano M. M. , Cecchetto Attilio , Carraro Paolo , Naso Agostino , De Silvestro Giustina , Plebani Mario , Abatangelo Giovanni , Donato Daniele , Cestrone Andriano , Giron Gianpiero , D'amico Davide F.
Published: April 2008

A liver transplant is considered today to be the only effective therapeutic solution for many otherwise intractable hepatic disorders. However, liver transplantation is beset by shortage of donors. Over the years, many liver support systems have been developed to supply the liver functions, mostly as a bridge to transplantation. Transplantation of isolated hepatocytes (HcTx) instead of whole liver has constituted one of the most appealing possibilities to treat several diseases. We compared two different models of HcTx in a surgical model of acute liver failure in pigs, using microencapsulated hepatocytes (MHcTx) and hepatocytes attached to a porcine biomatrix (PBMHcTx), both transplanted into peritoneum. The collected data were survival, laboratory findings, hemodynamic parameters, light microscopy, histology, MTT, and glycogen content. The group with PBMHcTx has a better outcome than the group with MHcTx (p < 0.05). Histology showed normal morphology of the hepatocytes, high glycogen content, 75% viability, positive MTT, and 95% adhesion of the hepatocytes to the biomatrix. Our biomatrix (PBM) provides cell-to-cell contact and interaction with extracellular matrix, which have been shown to play major roles in hepatocyte survival and physiologic regulation of gene expression, and guarantee a prompt engraftment and an adequate neovascularization. PBMHcTx is a useful method to treat acute liver failure and it indicates a possible liver-direct gene therapy in the treatment of inherited and acquired disorders.
Efficacy of a Polyurethane Foam/Spheroid Artificial Liver by Using Human Hepatoblastoma Cell Line (Hep G2)
Authors: Fukuda J. , Okamura K. , Nakazawa K. , Ijima H. , Yamashita Y. , Shimada M. , Shirabe K. , Tsujita E. , Sugimachi K. , Funatsu K.
Published: April 2008

We investigated the availability of human hepatoblastoma cell line (Hep G2), compared with human primary hepatocytes (HH) and porcine primary hepatocytes (PH), as a cell source for the hybrid artificial liver support system (HALSS) by using polyurethane foam (PUF). All three kinds of hepatocytes spontaneously formed spherical multicellular aggregates (spheroids) of 100–200 μm diameter in the pores of PUF within 3 days of culture. In a PUF stationary culture, Hep G2 spheroids recovered the ammonia removal activity that was lost in monolayer culture, although the removal for each unit cell number was about one tenth that of HH spheroids and about one eighth of PH spheroids. The synthesis activities of albumin and fibrinogen of each unit cell number of Hep G2 were also upregulated by PUF spheroid culture, and were about twice as high as in monolayer culture. The albumin secretion activity of Hep G2 spheroids was almost the same as that of PH spheroids. HH scarcely secreted these proteins in this experiment, probably because they were cultured in a serum-free medium. In the PUF module in a circulation culture, HH had high ammonia removal and low synthesis activities similar to stationary culture. Hep G2 proliferated to a high cell density, such as about 4.8 × 107 cells/cm3-module at 10 days of culture. Although Hep G2 spheroids had low ammonia removal activity in each cell, the removal rate in the PUF module was almost the same as for PH at 7 days of culture because of the high cell density culture by cell proliferation. The albumin secretion rate by Hep G2 in the PUF module also increased with cell proliferation and was about 10 times higher than the initial rate for PH at 7 days of culture. These results suggest that Hep G2 is a potential cell source for the PUF-HALSS.
Generation of Hepatocyte-Like Cells from Human Embryonic Stem Cells
Authors: Rambhatla Lakshmi , Chiu Choy-Pik , Kundu Pratima , Peng Yun , Carpenter Melissa K.
Published: April 2008

Use of human hepatocytes for therapeutic and drug discovery applications is hampered by limited tissue source and the inability of hepatocytes to proliferate and maintain function long term in vitro. Human embryonic stem (hES) cells are immortal and pluripotent and may provide a cell source for functional human hepatocytes. We report here that hES cells can be induced to differentiate into hepatocyte-like cells. Treatment with sodium butyrate induced hepatic differentiation as well as significant cell death, resulting in approximately 10–15% yield of a homogeneous population of cells. The differentiated cells have morphological features similar to that of primary hepatocytes and 70–80% of the cells express liver-associated proteins (albumin, alpha-1-antitrypsin, cytokeratin 8 and 18), accumulate glycogen, have inducible cytochrome P450 activity, and do not express alpha-fetoprotein. Because of the inherent proliferative capacity of hES cells, these cells may provide a reliable source of normal human hepatocytes for research and transplantation.
Activation of Macrophage-Associated Molecules after Brain Death in Islets
Authors: Toyama Hirochika , Takada Moriatsu , Suzuki Yasuyuki , Kuroda Yoshikazu
Published: April 2008

Islet transplantation is now established as an optional treatment for type I diabetes. However, rates of insulin independence in islet transplant recipients are still low. Although the major source of allograft is derived from brain-dead patient, the nonphysiologic state of brain death (BD) deteriorates organs such as liver and kidney. To determine the effects of BD on islets, a rodent model of BD has been used. Histologically, islets of BD rats showed decreased permeability and impaired integrity of the cell membranes. Flow cytometric analysis showed that CD11b/c-positive cells within islets were slightly increased in BD. This result suggests that BD induces macrophage infiltration into the islets. Moreover, RT-PCR revealed significant augmentation of macrophages-associated inflammatory molecules (IL-1β, IL-6, TNF-α, and MCP-1) in islets from a BD donor. Inducible nitric oxide synthase (iNOS) was weakly expressed, although not reaching statistical significance compared with control. Our results indicate that islets from a BD donor are immunologically activated and have a potential risk factor for early graft loss and a poor long-term function of grafts in clinical setting of islet transplantation. Immunomodulation, to eliminate intraislet immunocytes and/or activated macrophage-associated molecules, might be necessary for the better outcome after islet graft from BD donors.
Areal Density Measurement is a Convenient Method for the Determination of Porcine Islet Equivalents without Counting and Sizing Individual Islets
Authors: Lembert N. , Wesche J. , Petersen P. , Doser M. , Becker H. D. , Ammon H. P. T.
Published: April 2008

The determination of islet mass is important for the normalization of islet experiments in the laboratory and for the precise dosing of islets for transplantation. The common microscopical analysis is based on individual islet sizing, calculation of the frequency distribution, and conversion into islet equivalents (IEQ), which is the volume of a spherical islet with a diameter of 150 μm. However, islets are of irregular form, which makes this determination user dependent, and the analysis is irreproducible once the original sample is discarded. This routine technique of islet quantification was compared with the analysis of areal density measurements. It was assumed that the entire area occupied by islets can be expressed in IEQ without sizing and counting individual islets. Porcine islets were isolated by continuous digestion/filtration and purified by gradient centrifugation. Purified islets were stained with dithizone and were repeatedly pictured under the microscope with random area selection. A total of 51 pictures was taken from 11 different purifications and stained islets were detected by digital image analysis. The correlation coefficient (r) between both analyses was 0.977 with an underestimation of islet yield by areal density detection (slope: 0.75 ± 0.03). Areal density analysis per picture took about 1 min, which is about 10 times faster than the traditional method without increasing the method error (CV 2.1% vs. 2.7%). In summary, areal density measurements allow a rapid and reproducible estimation of IEQ without counting individual islets. It can be performed in a single step analysis without computer programming and is valuable for online determinations of islet yield preceding transplantation.
Cytotoxic Immune Response to a Xenogeneic Bioartificial Liver
Authors: Nyberg Scott L. , Amiot Bruce , Hardin Joseph , Baskin-Bey Edwina , Platt Jeffrey L.
Published: April 2008

Prior studies have suggested the possibility of immune-mediated death of xenogeneic hepatocytes in a bioartificial liver (BAL) during hemoperfusion. This study was designed to elucidate how immunity may cause death of xenogeneic hepatocytes in the BAL. Healthy dogs were treated with a BAL containing hollow fiber membranes with large pores (200 nm) or small pores (400 kDa). The immune response of recipient dogs to BAL therapy was monitored over 3 h of treatment. We observed significantly greater loss of viability of hepatocytes in the 200 nm group compared with the 400 kDa group (p < 0.001). Low viability after treatment with the large pore membrane was associated with positive staining for dog IgG, dog IgM, and dog complement on dead hepatocytes. Significant levels of dog antibody were detected in samples of BAL medium from the 200 nm group. These canine antibodies were cytotoxic to porcine hepatocytes. In contrast, medium from the 400 kDa group contained only trace levels of dog IgG and were noncytotoxic. We conclude that antibody-mediated cytotoxicity contributed to the death of hepatocytes during treatment with a xenogeneic BAL. Immune-mediated death of hepatocytes was reduced by increasing selectivity of the BAL membrane.
Maintenance of Functional Human Cancellous Bone and Human Hematopoiesis in NOD/SCID Mice
Authors: Hubin Frédérique , Humblet Chantal , Belaid Zakia , Greimers Roland , Boniver Jacques , Thiry Albert , Defresne Marie-Paule
Published: April 2008

Attempts were made to establish models to study interactions between marrow stromal cells and hematopoietic cells in vivo. The approach was to create a NOD-SCID-hu murine model of long-term human hematopoiesis by implantation of a human adult bone fragment. Nine to 12 weeks posttransplantation, human CD45+ cells were detected in the blood and the spleen of some mice. The histology of the human transplant showed that human bone fragment was viable at 9 weeks. Moreover, vessels of human origin, as assessed by immunohistochemical detection of human β2-microglobulin, were observed in the mouse tissue surrounding the transplanted human fragment.
Dose-Dependent Neurochemical and Functional Protection Afforded by Encapsulated CNTF-Producing Cells
Authors: Emerich Dwaine F.
Published: April 2008

Intracerebral delivery of hCNTF has shown considerable neuroprotective potential in animal models of Huntington's disease (HD). The present study describes the relationship between a range of hCNTF doses and the resulting behavioral and neurochemical (striatal ChAT and GAD activity) protection in a rodent model of HD. Encapsulated BHK delivering a range of hCNTF doses were implanted into the lateral ventricle ipsilateral to an intrastriatal quinolinic acid (QA) injection. Results demonstrated a dose-dependent effect of hCNTF with complete, partial, and no observable neuroprotection occurring with preimplant doses of hCNTF of 30.8, 8.6, and 0.8–2.1 ng hCNTF/24 h, respectively. These data continue to support the use of cellular delivery of hCNTF for HD and will facilitate the optimization of this approach in the clinical situation.
A Simple and Effective Method to Improve Intrasplenic Rat Hepatocyte Transplantation
Authors: Sigot Valeria , Mediavilla María G. , Furno Graciela , Rodríguez Joaquín V. , Guibert Edgardo E.
Published: April 2008

Transplanted hepatocytes integrate, survive, and express their specific functions in the liver parenchyma. The aim of this study was to determine whether a large number of hepatocytes could move from the spleen to the liver when the cells are injected together with sodium nitroprusside, and if the improved hepatocyte migration may be related with portal vein dilatation. Wistar rats were transplanted in the spleen with fluorescent-labeled hepatocytes alone or together with sodium nitroprusside. At 1, 3, 6, and 24 h after the transplant, the liver from recipient animals was removed and morphometric analyses were performed. Portal and arterial pressures were also measured immediately after intrasplenic injection of a solution of sodium nitroprusside, hepatocytes alone, or hepatocytes plus sodium nitroprusside. Intrasplenically injected sodium nitroprusside produced a transient drop in arterial pressure and a sustained reduction in portal pressure. During hepatocyte transplantation it increased the number of transplanted cells migrating to the liver after 3 h. Sodium nitroprusside simultaneously injected with hepatocytes in the spleen allowed more cells to migrate into the liver of the host animal without risk in animal survival.
Human Umbilical Cord Blood Mononuclear Cells for the Treatment of Acute Myocardial Infarction
Authors: Henning Robert J. , Abu-Ali Hamdi , Balis John U. , Morgan Michael B. , Willing Alison E. , Sanberg Paul R.
Published: April 2008

Cell transplantation is a new treatment to improve cardiac function in hearts that have been damaged by myocardial infarction. We have investigated the use of human umbilical cord blood mononuclear progenitor cells (HUCBC) for the treatment of acute myocardial infarction. The control group consisted of 24 normal rats with no interventions. The infarct + vehicle group consisted of 33 rats that underwent left anterior descending coronary artery (LAD) ligation and after 1 h were given Isolyte in the border of the infarction. The infarct + HUCBC group consisted of 38 rats that underwent LAD ligation and after 1 h were given 106 HUCBC in Isolyte directly into the infarct border. Immunosuppression was not given to any rat. Measurements of left ventricular (LV) ejection fraction, LV pressure, dP/dt, and infarct size were determined at baseline and 1, 2, 3, and 4 months. The ejection fraction in the controls decreased from 88 ± 3% to 78 ± 4% at 4 months (p = 0.03) as a result of normal aging. Following infarction in the infarct + vehicle group, the ejection fraction decreased from 87 ± 4% to 51 ± 3% between 1 and 4 months (p < 0.01). In contrast, the ejection fraction of the infarcted + HUCBC-treated rat hearts decreased from 87 ± 4% to 63 ± 3% at 1 month, but progressively increased to 69 ± 6% at 3 and 4 months, which was different from infarct + vehicle group rats (p < 0.02) but similar to the controls. At 4 months, anteroseptal wall thickening in infarct + HUCBC group was 57.9 ± 11.6%, which was nearly identical to the control anteroseptal thickening of 59.2 ± 8.9%, but was significantly greater than the infarct + vehicle group, which was 27.8 ± 7% (p < 0.02). dP/dtmaxincreased by 130% in controls with 5.0 μg of phenylephrine (PE)/min (p < 0.001). In the infarct + vehicle group, dP/dtmaxincreased by 91% with PE (p = 0.01). In contrast, in the infarct + HUCBC group, dP/dtmaxincreased with PE by 182% (p < 0.001), which was significantly greater than the increase in dP/dtmaxin the infarct + vehicle group (p = 0.03) and similar to the increase in the controls. Infarct sizes in the infarct + HUCBC group were smaller than the infarct + vehicle group and averaged 3.0 ± 2.8% for the infarct + HUCBC group versus 22.1 ± 5.6% for infarct + vehicle group at 3 months (p < 0.01); at 4 months they averaged 9.2 ± 2.0% for infarct + HUCBC group versus 40.0 ± 9.2% for the infarct + vehicle group (p < 0.001). The present experiments demonstrate that HUCBC substantially reduce infarction size in rats without requirements for immunosuppression. As a consequence, LV function measurements, determined by LV ejection fraction, wall thickening, and dP/dt, are significantly greater than the same measurements in rats with untreated infarctions.
G-CSF Promotes Bone Marrow Cells to Migrate into Infarcted Mice Heart, and Differentiate into Cardiomyocytes
Authors: Fukuhara Shinya , Tomita Shinji , Nakatani; Takeshi , Ohtsu Yoshinori , Ishida Michiko , Yutani Chikao , Kitamura Soichiro
Published: April 2008

A recent study showed that granulocyte-colony stimulating factor (G-CSF) treatment improved the infarcted cardiac function. Although mobilized stem cells may affect it, the mechanism is unclear. In this study, we investigated the origins of stem cells and phenotypic changes of the migrated cells, and evaluated the efficacy of G-CSF. Eighteen C57BL/6 mice were irradiated (900 cGy) and GFP mouse-derived bone marrow cells (GFP-BMC: 106 cells) were injected via a tail vein followed by splenectomy 4 weeks later. Ligation of the left descending coronary artery was performed 2 weeks later. Recombinant human G-CSF (200 μg/kg/day) was injected for 3 days before and 5 days after ligation (group 1, n = 10). Saline was injected in group 2 (n = 8). Four weeks after infarction, hearts and other organs were fixed for histology. The survival rate after postoperative day 3 in group 1 was 100%, while that in group 2 was 50% (p = 0.03). Bone marrow-derived GFP cells (BMD-GFP) in group 1 (103.3 ± 71.9/mm2) were located at the infarcted border area significantly more than those in group 2 (43.6 ± 23.7/mm2) (p < 0.0001). BMD-GFP cells were positive for troponin I (16.6%), myosin heavy chain-slow (16.7%), and nestin (8.8%) in group 1. Ki-67-positive BMD-GFP in group 1 (10.0 ± 7.0/mm2) were significantly more than those in group 2 (4.8 ± 6.1/mm2) (p = 0.01). G-CSF increased the survival rate after infarction. G-CSF promoted BMC to migrate into the infarcted border area. Bone marrow was one of the origins of regenerated cardiomyocytes.
Improved Histological Evaluation of Vascularity around an Immunoisolation Device by Correlating Number of Vascular Profiles to Glucose Exchange
Authors: Sörenby Anne , Rafael Ehab , Tibell Annika , Wernerson Annika
Published: April 2008

The aim of this study was to determine which vessels are important for the exchange of small molecules, such as glucose, from the microcirculation into an immunoisolation device. Reasonably, those vessels should be the ones of interest in histological evaluations. In a previous study, we examined the diffusion of glucose from the microcirculation into immunoisolation devices that had been implanted subcutaneously in rats for various times (i.e., 1, 2, and 4 weeks and 3 months). The glucose kinetic data were then correlated with the number of vascular profiles within 15 and 250 μm from the device. Significant correlations were found only at 250 μm. To examine the relation further between function and vascularization, we used the histological samples from the previous study and counted vascular profiles within various distances between 15 and 400 μm from the device. The number was then correlated with the already available glucose kinetic data. The highest correlations were found at 75 and 100 μm (p < 0.05). We therefore suggest that vascular profiles within 100 μm should be used when evaluating the vascularity of tissue surrounding an immunoisolation device. We also studied neovascularization asymmetries between the side of the membrane facing the skin and that facing the muscle. At 1 and 2 weeks about half of the devices were mainly vascularized on the side facing the skin, whereas the rest were equally vascularized on the two sides. At 3 months, all devices were well vascularized, and no striking vascularization asymmetries were seen.
Reevaluation of Bone Marrow-Derived Cells as a Source for Hepatocyte Regeneration
Authors: Cantz Tobias , Sharma Amar Deep , Jochheim-Richter Andrea , Arseniev Lubomir , Klein Christoph , Manns Michael P. , Ott Michael
Published: April 2008

We have investigated the contribution of intrasplenic bone marrow transplants or in vivo mobilized hematopoietic stem cells to the formation of hepatocytes in normal and injured liver. Direct intrasplenic injections of bone marrow mononuclear cells (5 × 10 cells), Sca1+/lin- hematopoietic stem cells (5 × 103) cells, and highly purified “side population” hematopoietic stem cells (5 × 103) derived from enhanced green fluorescent protein (EGFP)-transgenic mice [C57Bl/6-TgN(ActbEGFP)1Osb] were performed in normal C57Bl/6 mice (n = 6) and in C57Bl/6 mice following two thirds hepatectomy (n = 8). To test the effect of mobilized stem cells on transdifferentiation, C57Bl/6 mice (n = 12) were lethally irradiated and reconstituted with EGFP-positive bone marrow mononuclear cells in a second series of experiments. Eight to 12 weeks after bone marrow transplantation a subset of mice (n = 3 in each group) received either rhG-CSF for hematopoietic stem cell mobilization, rhG-CSF combined with an intraperitoneal application of carbon tetrachloride (CCl4) as hepatocyte regeneration stimulus, or CCl4 alone. All mice were completely perfused with PBS to remove circulating nonorgan cells for analyses 4 weeks later. Liver as well as heart, intestine, spleen, and kidney tissue was analyzed for the presence of EGFP-transgenic cells. In 100 sections (2.3 × 107 cells) of any recipient mouse no EGFP-positive hepatocytes were detected either by analysis of native EGFP fluorescence or by immunofluorescence analysis with anti-EGFP and antidipeptidyl peptidase (DPP) IV antibodies. EGFP-transgenic cells resembling heart, kidney, or intestinal cells could also not be proven. The results demonstrate that there is little or no contribution of bone marrow-derived cells to the regeneration of normal and injured liver in the animal models used. Thus, potential therapeutic prospects of hematopoietic stem cell therapy for liver disease have to be critically reassessed.
Viability of Allogeneic Bone Marrow Stromal Cells following Local Delivery into Patella Tendon in Rabbit Model
Authors: Ouyang Hong Wei , Goh James C. H. , Lee Eng Hin
Published: April 2008

Bone marrow stromal cells are potentially useful for tendon repair and regeneration. To provide lasting benefits, the seeded cells must survive implantation at local tendon sites. Our objective was to determine the in vivo fate of allogeneic bone marrow stromal cells (bMSCs) at different time points after implantation into patella tendon defects (i.e., at 2, 3, 5, and 8 weeks). The protocol involved the labeling of bMSCs with green fluorescent protein (GFP) or carboxyfluorescein diacetate (CFDA) before implantation. A window defect (5 × 5 mm) was created at the central portion of rabbit patella tendon and subsequently treated with GFP- or CFDA-marked bMSCs. The marked bMSCs were loaded into the window defect with fibrin glue. Upon sacrifice of the rabbits at the different time points, the implant site of the patellar tendon was immediately retrieved and the viability of the labeled cells was assessed under confocal microscopy. The results showed that the seeded bMSCs remained viable within the tendon wound site for at least 8 weeks after implantation. The cell morphology was changed from a round shape at 2 weeks to a spindle shape at 5 weeks after implantation. This study demonstrated that the bMSCs remained viable for prolonged periods after implantation and therefore have the potential to influence the formation and remodeling of neotendon tissue after tendon repair.
Transplantation of Cultured Salivary Gland Cells into an Atrophic Salivary Gland
Authors: Sugito T. , Kagami H. , Hata K. , Nishiguchi H. , Ueda M.
Published: April 2008

Patients with dry mouth have been treated with salivary substitutes and/or medications such as pilocarpine or cevimeline hydrochloride. These treatments temporarily relieve their symptoms and induce salivation from residual tissue. However, no treatment is available for the purpose of regenerating an atrophic gland. In this study, the feasibility of a cell transplantation therapy for the atrophic submandibular glands was investigated in rats. Further, the potential of cell differentiation into a useful phenotype was assessed by immunohistochemistry together with cell tracking with the fluorescent dye PKH 26. Rat submandibular glands were excised, and the salivary gland epithelial cells were cultured for 3 weeks with 3T3 cells as a feeder layer. Ductal ligation of the submandibular gland was employed to generate an atrophic gland. One week after the operation, the ligation was removed, and the cultured cells labeled with PKH 26 were injected into the atrophic submandibular glands. As a control, the cultured cells were also injected into normal submandibular glands. Two weeks after cell transplantation, the transplanted cells were detectable in both the experimental and control groups. The cells were clustered in the connective tissue between the lobules. Four weeks after transplantation, the labeled cells were detectable in the experimental group but not in the control group. In the atrophic glands, the scattered transplanted cells were observed over a broad area of the gland but localized mainly around the acini and ductal region. Immunostaining results showed a possible involvement of the transplanted cells in ductal regeneration, while neither myoepithelial nor acinar differentiations were observed within the 4 weeks since transplantation. This study demonstrated that cell transplantation to the salivary gland is feasible, and that the transplanted cells were selectively attracted to and remained in the damaged area without affecting normal tissue.
Optimization of Conditions for Clinical Human Hepatocyte Infusion
Authors: Fisher Robert A. , Bu Dawen , Thompson Melissa , Wolfe Luke , Ritter Joseph K.
Published: April 2008

Cytotoxicity and apoptosis are common problems in the isolation and storage of human hepatocytes. In vitro environments of hepatocytes during cell infusion may be critical to reducing cellular damage and enhancing cell viability. We examined the effects of donor liver histology (40–50% steatosis vs. normal), incubation time, temperature, and three solutions for infusion on banked primary human hepatocytes, by studying: trypan blue exclusion, AST release, LDH release, MTT assay, detection of DNA ladder, and a hepatocyte proliferation assay. In addition, the microstructure functions of the endoplasmic reticulum and mitochondria of the intact hepatocytes were determined by measuring correlates of UGT 1A1 and cytochrome P-450 3A (CYP3A4) activity. In general, hepatocyte viability decreased significantly within 60 min after thawing. Cells suspended in 5% dextrose lactated Ringers solution (D5LR) maintained greater cell viability. Hepatocytes from normal liver donors showed less AST and LDH enzyme leak in comparison with cells from fatty liver donors. Mild hypothermic temperature (32°C) inhibited cellular damage that otherwise significantly increased at 60 min. Hepatocytes did not proliferate until 12 h from thaw, regardless of supernatant or conditions of suspension. CYP3A4 activity and a marker for UGT 1A1 activity in hepatocytes from normal donor livers were higher than those from steatotic donor livers. These findings suggest that hepatocytes suspended for infusion after isolation from normal liver donors have normal biological functions and less cellular damage/necrosis in contrast with those isolated from fatty liver donors. These damages are inhibited significantly by maintaining hepatocytes at a mild hypothermic temperature (32°C). D5LR alone maintained the best cell viability for up to 60 min. Media of D5LR + adenosine and HMM were able to partially inhibit hepatocyte apoptosis in hepatocytes from steatotic livers.