bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential and Domain-Specific Associations Among Right-Wing Authoritarianism, Social Dominance Orientation, and Adolescent Delinquency
Authors: Oosterhoff Benjamin , Shook Natalie J. , Clay Russ , Metzger Aaron
Published: June 2017

Using a dual-process model (DPM) framework, this research examined whether right-wing authoritarianism (RWA) and social dominance orientation (SDO) are differentially associated with adolescent delinquency. In Study 1 ( N = 847; Mage = 15.96) and Study 2 ( N = 340; Mage = 16.64), adolescents completed measures of RWA, SDO, and engagement in different forms of delinquency. In Study 2, adolescents also reported their beliefs about obeying different laws. Across both studies, adolescents who endorsed greater RWA engaged in lower levels of delinquency and those who endorsed greater SDO engaged in higher levels of delinquency. Findings from Study 2 suggest that these associations are contingent on the domain-specific purpose of the law being violated and are also present with adolescents’ beliefs about their obligation to obey laws. These results extend the DPM, demonstrating that RWA and SDO are differentially linked with youth delinquency.
Individual Perceptions of Self-Actualization: What Functional Motives Are Linked to Fulfilling One’s Full Potential?
Authors: Krems Jaimie Arona , Kenrick Douglas T. , Neel Rebecca
Published: June 2017

Maslow’s self-actualization remains a popular notion in academic research as well as popular culture. The notion that life’s highest calling is fulfilling one’s own unique potential has been widely appealing. But what do people believe they are doing when they pursue the realization of their full, unique potentials? Here, we examine lay perceptions of self-actualization. Self-actualizing, like any drive, is unlikely to operate without regard to biological and social costs and benefits. We examine which functional outcomes (e.g., gaining status, making friends, finding mates, caring for kin) people perceive as central to their individual self-actualizing. Three studies suggest that people most frequently link self-actualization to seeking status, and, concordant with life history theory, what people regard as self-actualizing varies in predictable ways across the life span and across individuals. Contrasting with self-actualization, people do not view other types of well-being—eudaimonic, hedonic, subjective—as furthering status-linked functional outcomes.
The Materiality of Absence: Organizing and the case of the incomplete cathedral
Authors: Giovannoni Elena , Quattrone Paolo
Published: June 2017

This study explores the role of absences in making organizing possible. By engaging with Lefebvre’s spatial triad as the interconnections between conceived (planned), perceived (experienced through practice) and lived (felt and imagined) spaces, we challenge the so-called metaphysics of presence in organization studies. We draw on the insights offered by the project of construction of Siena Cathedral during the period 1259–1357 and we examine how it provided a space for the actors involved to explore their different (civic, architectural and religious) intentions. We show that, as the contested conceived spaces of the cathedral were connected to architectural practices, religious powers and civic symbols, they revealed the impossibility for these intentions to be fully represented. It was this impossibility that provoked an ongoing search for solutions and guaranteed a combination of dynamism and persistence of both the material architecture of the cathedral and the project of construction. The case of Siena Cathedral therefore highlights the role of absence in producing organizing effects not because absence eventually takes form but because of the impossibility to fully represent it.
Intensive Reading Interventions for Inadequate Responders in Grades K–3: A Synthesis
Authors: Austin Christy R. , Vaughn Sharon , McClelland Amanda M.
Published: June 2017

A subset of students fail to respond adequately to reading interventions. This synthesis systematically reviews studies in which students in grades K–3 responded inadequately to a Tier 2 reading intervention and were provided with a Tier 3 intervention. Descriptions of the Tier 3 reading interventions and effects are provided. To meet inclusion criteria, studies were required to (a) provide documented, multi-tiered reading interventions with at least one reading outcome measured; (b) include students in grades K–3 who previously responded inadequately to a Tier 2 intervention; (c) use experimental, quasi-experimental, or multiple-group designs; and (d) be peer reviewed and conducted in English. Twelve studies met inclusion criteria. Results demonstrate that students who responded inadequately to Tier 2 interventions can make significant growth from Tier 3 interventions compared with a control group of peers who were also inadequate responders, but often fail to catch up to their more responsive peers.
Relative Employment, Gender Beliefs, and Intimate Partner Coercion and Violence Against New Mothers Across Marital and Residential Contexts
Authors: Zito Rena C.
Published: June 2017

This research builds on prior studies of intimate partner victimization by examining the impact of women’s and men’s relative employment, gender traditionalism, and gender distrust on coercive control and physical victimization among married, cohabiting, and noncohabiting couples with infants. It merges feminist approaches that emphasize the gendered meaning of work, power, and violence with prior insights regarding differences in levels of intimate violence across family forms. Specifically, this research recognizes that there is variation across married, cohabiting, and dating contexts in the symbolic meaning of work, the salience of traditionalism, and the tenuous status of relationships that may activate gender distrust in the production of compensatory violence and control. Logistic regression models using baseline and Year 1 Fragile Families and Child Well-Being data ( n = 2,337) indicate that the predictors of coercive control differ across couple types, with the relative odds of coercion higher among couples in which only the woman is employed, but only when cohabiting. Consistent with expectations, men’s gender traditionalism increases coercive control, but only in the context of marriage. Relative employment and gender beliefs did not predict physical victimization among any couple types, but a moderating effect of men’s gender distrust on women’s sole employment was identified, such that status inconsistency in employment increases the relative odds of physical victimization only when the male partner is distrustful of women.
Chitosan–Polyvinyl Pyrrolidone Hydrogels as Candidate for Islet Immunoisolation: In Vitro Biocompatibility Evaluation
Authors: Risbud Makarand , Hardikar Anandwardhan , Bhonde Ramesh
Published: June 2017

The success of immunoisolation devices for islet transplantation depends on the nature of semipermeable membranes, which permit the crossover of micronutrients, glucose, and insulin and prevent the entry of immunocytes and other transplant rejection mechanisms. In the present study we examined the properties of chitosan–polyvinyl pyrrolidone (PVP) hydrogels for possible application as an immunoisolation device. Hydrogels with two different proportions of chitosan–PVP (M1 1:1 and M2 2:1, v/v) were synthesized by cross-linking with glutaraldehyde. Hydrogels were characterized for their hydrophilic nature, protein adsorption, diffusion properties, cytotoxicity, and islet compatibility. Hydrogel membranes were found to be hydrophilic as determined by high octane contact angle value (M1: 142.9 ±0.46; M2: 143.6 + 0.49). Protein adsorption on the hydrogels was found to be low (0.0143 + 0.0027 mg for M1 and 0.0136 ± 0.0049 mg for M2) compared to tissue culture polystyrene (TCPS) (0.0434 ± 0.001 mg) and pure chitosan (0.0214 ± 0.0025 mg) control. Hydrogel M1 was tested as a representative for diffusion studies. M1 allowed regulated transport of insulin and did not allow anti-insulin antibodies to pass through. In vitro biocompatibility of M1 and M2 was found to be excellent with no cytotoxic effects on the HeLa cells as determined by MTT and NR assay. Mouse islets cultured on the hydrogel membranes retained their integrity and intact morphology as assessed by image analysis study. Viability of islets cultured on hydrogels was comparable to that of controls (M1: 97%; M2: 90.4%) as assessed by trypan blue dye exclusion test. Islets retained their functionality when cultured on hydrogels, as judged by insulin secretion in response to glucose challenge (16.0 mM). Although in vivo experiments are awaited, the present study provides sufficient documentation to consider chitosan–PVP membranes as potential candidates for immunoisolation of islets.
Storage and Microencapsulation of Islets for Transplantation
Authors: Charles Kirk , Harland Robert C. , Ching Denise , Opara Emmanuel C.
Published: June 2017

Microencapsulation is an effective means of immunoisolation for pancreatic islet transplants. However, the process of isolating, purifying, encapsulating, and transplanting islets in a single day is labor intensive and difficult for routine use. There is an apparent need for reliable methods of islet storage, and cryopreservation has emerged as an attractive system of islet banking. While studies have shown that cryopreserved islets are viable when tested unencapsulated after thawing, it is not clear if the combination of freezing and encapsulation would affect islet function. The purpose of the present study was to determine the in vitro function of cryopreserved islets following thawing and microencapsulation. Islets were isolated from the pancreata of Sprague-Dawley rats and cryopreserved under liquid nitrogen for either 1 week or 1 month, following an overnight culture at 37CC. Upon thawing, the islets were tested either unencapsulated or after encapsulation in polylysine–alginate membrane. In all experiments islets were preperifused for 1 h at 37°C with a modified Krebs-Ringer bicarbonate buffer containing 3.3 mM (60 mg/dl) glucose and maintained at pH 7.4 by continuous gassing with 95% air/5% CO2. Following basal effluent sample collection on ice, the glucose concentration was raised to 16.7 mM (300 mg/dl). It was found that, within 10 min of high glucose stimulation, an average of twofold increase in insulin secretion (p < 0.01) was obtained in islets within or without microcapsules. We conclude that islets cryopreserved for 1 month prior to thawing and microencapsulation retained functional viability as determined in in vitro experiments.
Chemotaxis Activation of Peritoneal Murine Macrophages Induced by the Transplantation of Free and Encapsulated Pancreatic Rat Islets
Authors: Karsten V. , Tritschler S. , Mandes K. , Belcourt A. , Pinget M. , Kessler L.
Published: June 2017

The present study concerns the influence of the transplantation of free and encapsulated (AN69 membrane, Hospal) islets on the chemotaxis of peritoneal macrophages. Fifty free or encapsulated rat islets, cultured for 24 h, were transplanted in the peritoneal cavity of mice (n = 12). Three days after transplantation, the chemotaxis of peritoneal murine macrophages was tested towards formyl-methionyl-leucyl-phenylalanine (fMLP) and a culture medium conditioned for 3 days by free rat islets isolated from the same rat donor. In response to fMLP, the chemotactic indexes of macrophages from mice transplanted with free or encapsulated islets were 8.09 ± 2.10 and 9.45 ± 2.76, respectively. These values were significantly higher than those obtained when macrophages from untreated mice were tested (2.42 ± 0.23; p < 0.01). In response to culture medium conditioned by free islets, the transplanted encapsulated islets failed to enhance macrophage chemotaxis (2.41 ± 0.53) compared to transplanted free islets (7.00 ± 2.63; p < 0.01). Thus, encapsulation decreased the specific chemotactic activity of peritoneal macrophages induced by free islet transplantation, probably by prohibiting the diffusion of chemoattractants.
Determination of the Prime Electrostatic Endothelial Cell Transplantation Procedure for e-PTFE Vascular Prostheses
Authors: Bowlin Gary L. , Rittgers Stanley E. , Schmidt Steven P. , Alexander Thomas , Sheffer Daniel B. , Milsted Amy
Published: June 2017

The purpose of this study was to evaluate the extent of cellular adhesion (density and morphological maturation), cellular membrane damage, and cellular viability after an electrostatic transplantation of human umbilical vein endothelial cells (HUVECs) onto 6-cm segments of 4-mm I.D. e-PTFE (GORE-TEX®) vascular prostheses using a prototype electrostatic endothelial cell transplantation device (EECTD). The electrostatic transplantation parameters evaluated were the apparatus-applied voltage and transplantation time. By our definition, the combination of applied voltage and transplantation time that met the a priori criteria of: 1) maximum transplanted cellular viability, 2) maximum transplantation density, 3) maximum morphological maturation (degree of cellular flattening), and 4) minimal cellular membrane damage would be the prime transplantation procedure. The results of the experimentation indicated that the prime conditions for HUVEC transplantation were obtained when +1.0 V was applied for a transplantation time of 16 min. These conditions achieved an average viable graft surface coverage of 97.4 ± 1.6% with an average transplantation density of 73,540 ± 8,514 HUVECs/cm2. Furthermore, the transplanted HUVECs were morphologically mature (flattened) with minimal apparent cellular membrane damage (lysis or pitting). The overall clinical significance of this study is that viable endothelial cell transplantation to synthetic vascular grafts can be accomplished at high cellular densities and morphological maturation in 16 min using the EECTD. With the promising in vitro transplantation results, the next logical investigations will include additional in vitro evaluations (cellular retention upon shear stress exposure and biochemical assays) followed by in vivo evaluations to examine thromboresistance and influence on intimal/anastomotic hyperplasia.
Thymic Myoid Cells as a Source of Cells for Myoblast Transfer
Authors: Pagel C. N. , Morgan J. E. , Gross J. G. , Partridge T. A.
Published: June 2017

Transplantation of disaggregated myoblasts from normal donor to the muscles of a diseased host, or reimplantation of genetically modified host myoblasts, has been suggested as a possible route to therapy for inherited myopathies such as Duchenne muscular dystrophy, or to supply missing proteins that are required systemically in diseases such as hemophilia. With two exceptions, studies of myoblast transfer in the mouse have involved transplantation of donor myoblasts isolated from adult or neonatal skeletal muscle satellite cells. In this study we present evidence that thymic myoid cells are capable of participating in the regeneration of postnatal skeletal muscle, resulting in the expression of donor-derived proteins such as dystrophin and retrovirally encoded proteins such as β-galactosidase within host muscles. This leads us to conclude that thymic myoid cells may provide an alternative to myoblasts derived from skeletal muscle as a source of myogenic cells for myoblast transfer.
Technique for Bilateral Intracranial Implantation of Cells in Monkeys Using an Automated Delivery System
Authors: Bankiewicz Krys S. , Bringas John , Pivirotto Phillip , Kutzscher Ethan , Nagy Dea , Emborg Marina E.
Published: June 2017

Intracerebral grafting combined with gene transfer may provide a powerful technique for local delivery of therapeutic agents into the CNS. The present study was undertaken to: (i) develop a reliable and reproducible automated cell implantation system, (ii) determine optimal implantation parameters of cells into the striatum, (iii) determine upper safe limits of cellular implantation into the neostriatum of monkeys. Autologous fibroblasts were infused into six sites of the striatum in nonhuman primates (Macaca mulatta, n = 11). Twenty-six-gauge cannulae were inserted vertically through cortical entry sites into the striatum (two sites in the caudate nucleus and four sites in the putamen) at predefined coordinates based on magnetic resonance imaging (MRI). The cannulae were guided by an electronically operated, hydraulic micropositioner and withdrawn at controlled rates, while cells (5, 10, 20, 40, or 80 μl/site) were infused simultaneously. Varying infusion rates and cell concentrations were also evaluated. Visualization and evaluation of graft placement were performed using contrast MRI at 3–5 days postsurgery. Animals were monitored for signs of clinical complications and sacrificed 2 weeks following surgery. Postimplantation MRI revealed a tissue mass effect of the implant with shifting of midline, edema, and infiltration of the white tracts at 40 and 80 μl/site. In addition, these animals developed transient hemiparesis contralateral to the implant site. MRI of animals grafted with 20 μl/site exhibited columnar-shaped implants and evidence of infiltration into white matter tracts possibly due to a volume effect. No clinical side effects were seen in this group. At 14 days postsurgery, MRI scans showed consistent columnar grafts (measuring approximately 5 mm in height) throughout the striatum in animals implanted with 5 or 10 μl/site. No signs of clinical side effects were associated with these volumes and postmortem histological examination confirmed MRI observations. Optimal surgical parameters for delivery of cells into the striatum consist of a graft volume of 10 μl/site, an infusion rate of 1.6 μl/min, a cell concentration of 2.0 × 105 cells/μl, and a cannula withdrawal rate of 0.75 mm/min. These results show that infusion of cells into the striatum can be done in a safe and routine manner.
Behavioral Evaluation of Hemiparkinsonian MPTP Monkeys following Dopamine Pharmacological Manipulation and Adrenal Co-Graft Transplantation
Authors: Howell Leonard L. , Byrd Larry D. , Mcdonough Ann M. , Iuvone P. Michael , Bakay Roy A. E.
Published: June 2017

Bradykinesia and rigidity are the symptoms that most directly correlate with loss of striatal dopamine in Parkinson's disease. In the hemiparkinsonian (HP) monkey, this is represented by paucity of movement as measured by computerized movement analysis, diminished manual dexterity on clinical examination, and diminished performance on operant behavioral tasks. The present study used an MPTP-induced HP model in rhesus monkeys to evaluate the effectiveness of adrenal medullary and peripheral nerve co-grafts in diminishing parkinsonian symptoms. Unoperated controls (N = 4), surgical controls with caudate lesioning (N = 4), and caudate co-grafted (N = 4) HP monkeys demonstrated diminished movement in the home cage following MPTP. This behavior persisted in unoperated controls, but improved in both surgical control and co-grafted monkeys. Functional hand dexterity evaluations demonstrated similar impairment in all three groups, but only surgical controls and co-grafted monkeys demonstrated improvement. In general, rotational behavior in response to apomorphine was consistent with recovery of function in surgical controls and co-grafted monkeys, but marked between-subject variability precluded group statistical analyses. None of the monkeys could perform the operant task using the affected limb following MPTP. However, the performance of two co-grafted animals demonstrated partial recovery. L-dopa improved operant performance, demonstrating a dopaminergic component to the task. The results demonstrate recovery of behavioral function after surgical treatment, with adrenal co-grafted monkeys showing the greatest degree of improvement.
Acutely Sodded Expanded Polytetrafluoroethylene Grafts Produce Only Prostacyclin: A Qualitative Difference from Saphenous Veins
Authors: Desai Sudhen B. , Cable David G. , Phillips Michael R. , Schaff Hartzell V.
Published: June 2017

Select subsets of patients require prosthetic graft material for revascularization. Although arterial prosthetic grafts of large caliber perform acceptably, grafts of <6 mm exhibit a high attrition rate. Microvessel endothelial sodding, a method resulting in the lining of prosthetic grafts with autologous endothelium, improves graft patency; however, aggressive antiplatelet therapy is still required, because terminating an antiplatelet regimen accelerates graft attrition. The present investigation was designed to address the acute production of vasoactive substances in microvessel endothelial cell sodded expanded polytetrafluoroethylene (ePTFE) grafts in an attempt to delineate a possible mechanism behind the continued requirement for antiplatelet therapy. Equal lengths of acutely sodded ePTFE grafts (canine falciform ligament source) and saphenous veins (SV) (canine source) were evaluated by superfusion bioassay. Basal secretion from ePTFE grafts relaxed the biodetector ring 1 ± 3%, whereas SV relaxed the ring 10 ± 3% (p < 0.05, ePTFE vs. SV). Relaxation with acetylcholine stimulation was 49 ± 7% in grafts and 50 ± 10% in veins (p = NS). Calcium ionophore stimulation produced relaxation of 37 ± 9% from ePTFE grafts and 100 ± 23% from SV (p < 0.05). Indomethacin added to perfusate reduced relaxations from sodded ePTFE grafts to 20.2 ± 9.2% with acetylcholine stimulation and 12.5 + 4.3% with calcium ionophore (p < 0.05 vs. control); addition of NG-monomethyl-L-arginine (L-NMMA) had no effect on the release of vasoactive substances from ePTFE grafts. In contrast, relaxations of effluent from SV stimulated by acetylcholine and calcium ionophore were significantly attenuated with indomethacin and L-NMMA (p < 0.05 vs. control). Scanning electron microscopy demonstrated confluent endothelium in SV and a nonconfluent endothelial cell layer in grafts. Acutely sodded ePTFE grafts produce vasoactive substances that quantitatively and qualitatively differ from those produced by canine SV. The ePTFE grafts produce mainly prostanoids, whereas SV produce both nitric oxide and prostanoids. The endothelial cell isolation procedure and absence of immediate graft luminal confluence may contribute to the observed differences.
Patient Survival and Cardiovascular Events after Kidney–Pancreas Transplantation: Comparison with Kidney Transplantation Alone in Uremic IDDM Patients
Authors: La Rocca Ennio , Fiorina Paolo , Astorri Ettore , Rossetti Claudio , Lucignani Giovanni , Fazio Ferruccio , Giudici Daniela , Castoldi Renato , Bianchi Giuseppe , Di Carlo Valerio , Pozza Guido , Secchi Antonio
Published: June 2017

In diabetic patients cardiovascular morbidity and mortality is still a major problem. Our aim was to study the effect of kidney–pancreas transplantation on survival, cardiovascular events, and causes of death in diabetic type I uremic patients. Three hundred and thirty-three uremic IDDM patients were enrolled in our waiting list for kidney–pancreas transplantation: 107 underwent kidney–pancreas transplantation (KP), 34 underwent kidney transplantation alone (KA), whereas 192 patients remained on dialysis (WL). Actuarial survival and causes of death were recorded over a period of 7 years. Seven-year survival rate was 75% for the KP group, 63% for the KA group, and 37% for the WL group (p = 0.001). Cardiovascular death rate was 9.8% in the KP group, 17.6% in the KA group, and 18.1% in the WL group (KP vs. WL, p = 0.05). Rate of acute myocardial infarction in the KP group was lower than in the KA group (2.4% vs. 17.6%, p = 0.005) as well as rate of acute pulmonary edema (0.8% vs. 23.5%, p = 0.0001) and rate of hypertensive patients at 1 (40.9% vs. 85.0%, p = 0.0001) and at 2 years (57.6% vs. 80%, p = 0.03). Kidney–pancreas transplant helped to obtain euglycemia with positive effects on survival and cardiovascular events.
Cryopreservation in Situ of Cell Monolayers on Collagen Vitrigel Membrane Culture Substrata: Ready-to-Use Preparation of Primary Hepatocytes and ES Cells
Authors: Miyamoto Yoshitaka , Enosawa Shin , Takeuchi Tomoyo , Takezawa Toshiaki
Published: June 2017

Cryopreservation is generally performed on cells in suspension. In the case of adherent cells such as hepatocytes, a loss of their ability to attach is a more serious problem than a decreased viability after cryopreservation. We herein report a novel technology of direct in situ cryopreservation of cells cultured on collagen vitrigel membranes, which have excellent mechanical strength and can be easily handled by tweezers even when coated with cultured cells. Rat primary hepatocytes, mitomycin C-treated mouse fibroblasts (feeder cells for ES cells), and mouse ES cells on the feeder cells were cultured on collagen vitrigel membranes for 1 day. The membranes with cells attached were then plucked up from the dish, soaked in cryopreservation medium containing 10% dimethyl sulfoxide, frozen using a controlled-rate freezer, and transferred to liquid nitrogen. The cells cultured on plastic cell culture dishes were also frozen as controls. After storage in liquid nitrogen for periods from 1 week to 3 months, the cryopreserved membranes with the cells still attached were thawed by adding warmed culture medium. Cell viability estimated by morphology and functional staining with calcein showed significant improvement in comparison to cells cryopreserved without the collagen vitrigel membrane. The recoveries of living cells after cryopreservation were 26.7%, 76.2%, and 58.6% for rat hepatocytes, mitomycin C-treated mouse fibroblasts, and mouse ES cells on collagen vitrigel membranes, respectively. In contrast, essentially no cells at all remained on the plastic cell culture dishes after thawing. Because adherent cell storage under these conditions is very convenient, the use of this technique employing collagen vitrigel membranes should be generally applicable to the cryopreservation of adherent cells that are otherwise problematic to store as frozen stocks.
Neovascularization Induced around an Artificial Device Implanted in the Abdomen by the Use of Gelatinized Fibroblast Growth Factor 2
Authors: Yuasa Takeshi , Rivas-Carrillo Jorge D. , Navarro-Alvarez Nalú , Soto-Gutierrez Alejandro , Kubota Yasuhiro , Tabata Yasuhiko , Okitsu Teru , Noguchi Hirofumi , Matsumoto Shinichi , Nakaji Shuhei , Tanaka Noriaki , Kobayashi Naoya
Published: June 2017

The development of a bioartificial pancreas (BAP) with immunoisolating fashion has been gaining attention as a new method for treating diabetes. We have been proceeding with the development of a bag-type BAP that can be easily implanted and that allows for the optional injection or rejection of cells at any time. If fibrosis develops around a BAP device, then the permeability of substances transmitted through a semipermeable membrane will decrease, thereby reducing the reactivity with glucose, so it is necessary for the material of the device to have an excellent histocompatibility. Furthermore, in order to improve the efficacy of BAP treatment, it is important to maintain an environment of ample blood flow around the device. We have created a bag-type device for BAP that is 20 × 20 mm in size and comprises two layers of membranes. We have used an EVAL membrane for the outer membrane of the two layers. The EVAL membrane is a semipermeable membrane with good insulin permeability, which functions as an immunoisolation membrane. The inner membrane consists of PAU-coated HD-PE (nonwoven material processed with polyaminourethan) and it is designed to function as a scaffold for cells. We used Lewis rats to determine whether the effectiveness of fibroblast growth factor 2 (bFGF) can be improved by concomitantly using bFGF with a capacity for blood vessel regeneration as well as bFGF immersed in a sheet of gelatin. We placed the BAP in the abdominal cavity and covered it with the greater omentum. We were able to significantly increase the blood flow and the number of new blood vessels in the tissue surrounding the BAP device by using gelatinized bFGF. There were only a few instances of fibrosis as a biological reaction to the EVAL membrane, and the infiltration of inflammatory cells was mild. There were no adverse effects related to implantation of the device. We confirmed in this study that the use of an implantable BAP device and bFGF allowed for a better blood flow around the BAP device. There were only minor instances of fibrosis and inflammation reaction around the BAP, thus indicating the BAP that we are currently developing to have an excellent histocompatibility.
Tissue Plasminogen Activator Expression in Endothelial Cells Exposed to Cyclic Strain in Vitro
Authors: Iba Toshiaki , Sumpio Bauer E.
Published: June 2017

The effects of cyclic strain on the production of tissue plasminogen activator (tPA) and type 1 plasminogen activator inhibitor (PAI-1) by cultured endothelial cells (EC) were examined. Human saphenous vein EC were seeded in selective areas of culture plates with flexible membrane bottoms (corresponding to specific strain regions) and grown to confluence. Membranes were deformed by vacuum (-20 kPa) at 60 cycles/min (0.5 s strain alternating with 0.5 s relaxation in the neutral position) for 5 days. EC grown in the periphery were subjected to 7-24% strain, while cells grown in the center experienced less than 7% strain. The results show a significant increase in immunoreactive tPA production on days 1, 3 and 5 compared to day 0 in EC subjected to more than 7% cyclic strain. There was no significant elevation of tPA in the medium of EC subjected to less than 7% strain. tPA activity could only be detected in the medium of EC subjected to more than 7% cyclic strain. PAI-1 levels in the medium were not significantly different in either group. In addition, immunocytochemical detection of intracellular tPA and messenger ribonucleic acid (mRNA) expression of tPA (assessed by the reverse transcriptase polymerase chain reaction utilizing tPA specific sense and antisense primers) was significantly increased in EC subjected to more than 7% cyclic strain. We conclude that a 60 cycles/min regimen of strain that is greater than 7% can selectively stimulate tPA production by EC in vitro and may contribute to the relative nonthrombogenicity of the endothelium in vivo.
Entrapment of Cultured Pancreas Islets in Three-Dimensional Collagen Matrices
Authors: Chao Seh-Huang , Peshwa Madhusudan V. , Sutherland David E.R. , Hu Wei-Shou
Published: June 2017

In vitro culture of islets of Langerhans decreases their immunogenecity, presumably by eliminating passenger leukocytes and other Ia+ presenting cells within the islets. Islets cultivated in petri dishes either at 37°C or at 25°C gradually disintegrate during culture in a time-dependent manner which is related to the free-floating condition of the islets. Also, a fraction of the islets disperse as single cells and beta-cell aggregates or adhere to the bottom of the culture dishes. Thus, the retrieval rate of transplantable islets is dampened due to their disintegration and spontaneous dispersion in conventional petri dish cultures.

Entrapment of freshly harvested islets of Langerhans in a three-dimensional collagen matrix was studied as an alternative method for islet cultivation. The contraction of collagen fibrils during in vitro culture counteracts the dispersion of islets and helps in maintaining their integrity while in culture. It was observed that the entrapped islets maintain satisfactory morphology, viability, and capability of glucose-dependent insulin secretion for over 2 wk. The oxygen consumption rate and glucose metabolism of these islets was not deranged when entrapped in collagen. Also, the retrieval of islets is easier and more efficient than that observed in conventional culture systems.

Our results indicate that culture of islets in three-dimensional collagen gels can potentially develop into an ideal system applicable to clinical transplantation of cultured islets or beta-cell aggregates.
A Primate Model of Huntington'S Disease: Functional Neural Transplantation and Ct-Guided Stereotactic Procedures
Authors: Schumacher James M. , Hantraye Philippe , Brownell Anna-Lisa , Riche Danielle , Madras Bertha K. , Davenport Paula D. , Maziere Mariannick , Elmaleh David R. , Brownell Gordon L. , Isacson Ole
Published: June 2017

In this article, we show that 1) computed tomographic (CT)-guided stereotactic infusion of an excitotoxin into the striatum of a nonhuman primate provides a useful neuropathologic and behavioral model for Huntington's disease. 2) High-resolution positron emission tomography (PET) can be used to image the decreased glucose utilization and the preservation of dopaminergic terminals in the lesioned striatum by using 2-fluoro-deoxy-D-glucose (2FDG) and N-(C-11)-methyl-2-beta-carbomethoxy-3-beta-phenyl tropane (CPT) as tracers. 3) Transplantation of crossspecies striatal fetal tissue into the lesioned caudate-putamen reduces many of the abnormal motor movements and behavioral changes seen in the Huntington's disease primate model. 4) Graft rejection results in the return of the abnormal signs of the pregrafted state. These results indicate that treatment of the neuronal deficit in Huntington's disease can involve intervention at the local neuronal circuit level. CT-guided stereotactic implantation of cells that might protect or replace this defective circuitry may eventually provide an effective treatment for Huntington's disease.
Neural Transplantation: Prospects for Clinical use
Authors: Freed William J.
Published: June 2017

Neural transplantation has been extensively applied in Parkinson's disease, including numerous clinical studies, studies in animal models, and related basic research on cell biology. There is evidence that the clinical trials of both adrenal medulla transplantation and fetal substantia nigra transplantation have produced a detectable clinical effect, although it is not yet clear whether the clinical benefit is sufficient to justify a more widespread application of these procedures. Studies of long-term outcome and quantitative tests are important in assaying the degree of benefit produced by transplantation procedures in Parkinson's disease and for developing improved and refined procedures. Other disease-related applications of neural transplantation are beginning to be developed. These include Huntington's disease, chronic pain, epilepsy, spinal cord injury, and perhaps even demyelinating diseases and cortical ischemic injury. Although most of these applications lie in the future, it is not too soon to begin to consider the scientific justification that should be required for initiation of human clinical trials.
Fetal Islet Cell Transplants: Promises and Limits of the Experience in the Eastern Countries
Authors: Farkas Gyula
Published: June 2017

The fetal pancreas is a potential source of islet ceils for transplantation. Despite marked advances in experimental islet grafting over the past two decades, successful clinical fetal transplantation seems to be very rare. The possible reasons for the failure of this transplantation are discussed. The review summarizes the development of a method for the isolation of fetal tissue, and the factor influencing the growth and differentiation of isolated fetal islets prior to and after transplantation. Finally, a brief overview is given of the status of clinical human pancreatic transplantation and a possible key to successful grafting.
Sertoli Cell-Enriched Fractions in Successful Islet Cell Transplantation
Authors: Selawry Helena P. , Cameron D.F.
Published: June 2017

Prolonged survival of Islet- allo- and xenografts can be induced following implantation of the islets into the abdominal testis of diabetic rats. We previously showed that a factor released by Sertoli cells appears to be responsible for the protection of the intratesticular islet allo- and xenografts against rejection. The aim of this study was to examine whether an immunologically privileged site can be established in an organ site in vivo, other than the testis, such as the renal, subcapsular space, to make feasible the grafting of female recipients as well. A total of 36 male and 21 female, diabetic, PVG rats were divided into six different treatment groups: 1) Six male rats were grafted with islets from Sprague-Dawley (S-D) donor rats only. 2) Ten male rats were grafted with islets from (S-D) donors and were then given a short course of cyclosporine (CsA) posttransplantation. 3) Ten male rats were grafted with islets from (S-D) donors and with Sertoli cell-enriched fractions (SEF) from PVG donors but without CsA. 4) Ten male rats were grafted with a combination of islets from (S-D) and SEF from (PVG), donors, respectively, and CsA. 5) Ten female rats were given an identical combination of cells and CsA as depicted for group 5.6) Ten female rats were grafted with a combination of islets and SEF, both cell types from S-D donors, and CsA. The results showed that 70% to 100% of the grafted rats in groups 1, 2, and 3 remained hyperglycemic. Prolonged normoglycemia in excess of 100 days was induced in more than 75% of the grafted rats only in groups 4,5, and 6, or in those animals who were grafted with a combination of islets and SEF and who were given a short course of CsA as well. Electron microscopic examination of the grafted tissues showed the presence of intact beta cells and of cells with features characteristic of Sertoli cells. Our results suggest that 1) the protection of islet allografts in nonimmunologically privileged site can be achieved in male and female rats by means of the simultaneous transplantation of Sertoli cells. 2) Sertoli cells apparently maintain the capacity to secrete an immune inhibitor in organ sites other than the testis. We conclude that it is feasible to create an immunologically privileged site for the transplantation of isolated islets in male and female diabetic recipients without the need for sustained immunosuppression.
Hepatocellular Transplantation for Metabolic Support in Experimental Acute Ischemic Liver Failure in Rats
Authors: Takeshita Kazuyoshi , Ishibashi Haruaki , Suzuki Masayuki , Kodama Masashi
Published: June 2017

The function of transplanted hepatocytes in acute ischemic liver failure was studied in an experimental model using rats. Ischemic liver failure was induced by occlusion of the proximal portal vein and hepatic artery immediately following extracorporeal portofemoral venous bypass. All rats were bred in a closed colony. Rats in Group 1 were untreated and served as controls (n = 10). Rats in Group 2 received an intrasplenic transplant of hepatocytes (1 × 107 cells) 48 h before liver ischemia (n = 10). Serum ammonia and blood glucose were measured before, and 1 h after, ischemia. Serum ammonia was significantly higher than normal (Group 1, 930 μg/dL vs < 110 μg/dL) after liver ischemia. On the other hand, serum ammonia in group 2 also was elevated (355 μg/dL), but significantly less so than in Group 1 (p < 0.001). Blood glucose was lower in both groups after liver ischemia, compared to normal (50-100 mg/dL), but it was higher in Group 2 (30 mg/dL) than in Group 1 (14 mg/dL, p < 0.01). Liver histology 1 h after ischemia showed similar degrees of necrosis in the two groups. Transplanted hepatocytes were viable, and clearly identified in the splenic parenchyma after ischemia. Intrasplenic transplanted hepatocytes provide temporary metabolic support of acute ischemic liver failure in rats, as reflected by enhanced ammonia removal and gluconeogenesis.
The Kinetics of SCID-hu Reconstitution: A Comparison between Human Splenocytes and Peripheral Blood Leucocytes
Authors: Thirdborough Stephen M. , Chamberlain Julie C. , Swift Sue M. , James Roger F. L. , London Nicholas J. M.
Published: June 2017

Although preliminary studies have shown that the severely combined immunodeficient (SCID)-hu mouse can reject allo tissue, they have also highlighted the current limitations of the SCID-hu model. These limitations are the need for unambiguous identification of human cells in the SCID mouse and the variability of the reconstitution efficiency. The purpose of this study was to follow the kinetics of SCID-hu reconstitution, comparing human splenocytes (SC) with peripheral blood leucocytes (PBL) to ascertain whether the presence of post-thymic progenitor cells in SC improved the efficiency of reconstitution. SCID mice were injected intraperitoneally with 5 × 107 PBL from five normal volunteers, and with 5 × 107 SC from 5 organ donor spleens. Two animals per donor were culled on weeks 2, 4, 8, and 16, and the frequency and level of SCID-hu reconstitution assessed by flow cytometric analysis of peritoneal cells and splenic leucocytes. Total serum immunoglobulin levels were measured fortnightly to follow the kinetics of B lymphocyte reconstitution. A marked degree of variability was seen in the frequency and extent of reconstitution, regardless of the source of lymphocytes. However, in comparison with PBL, human SC, predominantly T cells, were able to persist and increase in number, migrating from the peritoneal cavity to secondary lymphoid tissue. We conclude that human SC provide a better source of human lymphoid cells for SCID reconstitution than PBL.
Cell Transplantation in Liver-Directed Gene Therapy
Authors: Raper Steven E. , Wilson James M.
Published: June 2017

Somatic cell gene therapy is a new field of biomedical research that encompasses a variety of traditional basic research and clinical disciplines. This new approach to therapeutics has the potential to prevent, treat, or cure a variety of inherited and acquired diseases. Two divergent strategies of hepatocyte transplantation are being employed in animal models and clinical trials in an attempt to correct genetic deficiencies. Allogeneic hepatocyte transplantation has two main advantages over autologous cell transplantation. First, invasive surgical procedures are not required in the recipient. Second, allogeneic cells can be administered repetitively, so that multiple harvests are not necessary. The major drawbacks to allogeneic hepatocyte transplants are rejection and the risks of immunosuppression. Although there is no clinical experience with the treatment of genetic disease by allogeneic hepatocyte transplantation, a variety of animal models have been characterized, including the Gunn rat (UDP-glucuronosyl transferase deficient), the Nagase analbuminemic rat, and the Watanabe heritable hyperlipidemic rabbit (LDL receptor deficient). The use of genetically corrected autologous cells represents a different and more elegant approach to the correction of inherited disease. A segment of liver is harvested from the affected individual. Recombinant retroviruses are used to transduce normal genes— with a variety of promoter/enhancer constructs —into the patients own hepatocytes. The genetically corrected hepatocytes are then transplanted back into the patient. This approach, known as ex vivo gene therapy, eliminates the risk of rejection and the need for immunosuppression. The safety and efficacy of this approach has been proven in a variety of preclinical animals models, including Watanabe rabbits, dogs, and Papio spp. A clinical trial for the treatment of familial hypercholesterolemia is currently in progress. A number of approaches for the reintroduction of hepatocytes into the recipient have been proposed, including cathetermediated delivery into the inferior mesenteric vein, the umbilical vein, or into the spleen. Candidate diseases, which are likely to result in the first clinical trials include familial hypercholesterolemia, ornithine transcarbamylase deficiency, Crigler-Najjar syndrome, alpha]-antitrypsin deficiency, and phenylketonuria.
Expansion of Activated Lymphocytes Obtained from Renal Cell Carcinoma in an Automated Hollow Fiber Bioreactor
Authors: Hillman Gilda G. , Wolf Martin L. , Montecillo Emily , Younes Elia , Ali Esa , Pontes J. Edson , Haas Gabriel P.
Published: June 2017

Immunotherapy using IL-2 alone or combined with activated lymphocytes has been promising for metastatic renal cell carcinoma. Cytotoxic lymphocytes can be isolated from tumors, expanded in vitro with IL-2, and adoptively transferred back into the tumor-bearing host. These cells can also be transduced with the genes coding for cytokines for local delivery to tumor sites. A major drawback in adoptive immunotherapy is the cumbersome and expensive culture technology associated with the growth of large numbers of cells required for their therapeutic effect. To reduce the cost, resources, and manpower, we have developed the methodology for lymphocyte activation and expansion in the automated hollow fiber bioreactor IMMUNO*STAR™ Cell Expander (ACT BIOMEDICAL, INC). Tumor Infiltrating Lymphocytes (TIL) isolated from human renal cell carcinoma tumor specimens were inoculated at a number of 108 cells in a small bioreactor of 30 ml extracapillary space volume. We have determined the medium flow rates and culture conditions to obtain a significant and repeated expansion of TIL at weekly intervals. The lymphocytes cultured in the bioreactor demonstrated the same phenotype and cytotoxic activity as those expanded in parallel in tissue culture plates. Lymphocyte expansion in the hollow fiber bioreactor required lower volumes of medium, human serum, IL-2 and minimal labor. This technology may facilitate the use of adoptive immunotherapy for the treatment of refractory malignancies.
The Mesentery as a Laminated Vascular Bed for Hepatocyte Transplantation
Authors: Johnson Lynt B. , Aiken John , Mooney David , Schloo Betsy L. , Griffith-Cima Linda , Langer Robert , Vacanti Joseph P.
Published: June 2017

The small bowel mesentery provides a unique structure of a large vascularized surface area to support hepatocyte transplantation. Cell-seeded polymeric matrices can be juxtaposed in a relatively atraumatic manner between leaves of mesentery such that adequate exchange of nutrients and diffusion of gases can proceed in the interim while neovascularization occurs. Hepatocytes obtained from (RHA) Wistar rats by collagenase perfusion were seeded onto non-woven filamentous sheets of polyglycolic acid 1 × 3 cm in size and 2 mm thickness to a density of 500,000 cells/cm2. Twenty-six recipient Gunn rats (UDP-glucuronyl transferase deficient) underwent laparotomy. Hepatocyte-ladened polymer sheets were placed between leaves of mesentery. Eight sheets were placed per animal and the leaves were approximated, creating a functional implant 1 × 3 × 2 cm. Biopsies between 5-99 days after implantation revealed neovascularization, moderate inflammatory reaction and the presence of viable hepatocytes in 96% (25/26). Immunoperoxidase studies using anti-albumin antibody substantiated hepatocyte specific function in implants. HPLC profiles of bile from Gunn rats transplanted with hepatocytes from congeneic (RHA) rats demonstrated the presence of bilirubin conjugates. There were no conjugation fractions seen in control gunn rats without hepatocyte transplantation. Although total serum bilirubin did not significantly decrease, conjugated bilirubin was identified in 46% (12/26) animals after transplantation with congeneic hepatocytes. We conclude that the mesentery of the small bowel provides a large vascularized surface for cell transplantation. Large numbers of metabolically active hepatocytes can engraft, vascularize, and show function. The mesentery may be a potential bed for clinical hepatocyte transplantation.