bluuebunny/crossref_metadata_2025 huggingface dataset:
Strafrechtliche Haftung für prozessbedingte sekundäre Viktimisierung
Authors: Kölbel Ralf
Published: August 2007

I. Innerprozessualer Opferschutz durch Strafrecht oder Prozessrechtsreform?

Wer durch ein Verbrechen geschädigt wird, ist an dessen strafrechtlicher Verarbeitung in aller Regel als Zeuge beteiligt. Diese Inanspruchnahme erscheint für den modernen Strafprozess als geradezu typisch. Dennoch sieht die gegenwärtige rechtspolitische Diskussion darin zugleich einen Anlass zur Sorge. Man fürchtet, das Opfer könnte im Zuge seiner Verfahrenseinbindung weiteren Schaden erleiden. So wird auch in der bundesdeutschen Debatte davon ausgegangen, dass es in der strafrechtlichen Hauptverhandlung bisweilen zu einer Verletzung der Opferzeugen komme, weshalb eine legislative Gegensteuerung notwendig sei. Entsprechende Initiativen stehen bis heute auf der Tagesordnung, wobei man sich nach einigen Prozessrechtsänderungen allerdings zunehmend darauf verlegt, eine unzureichende Wahrnehmung dieser neuen prozessualen Möglichkeiten zu monieren.
Subverting Eden: Ambiguity of Evil and the American Dream in Blue Velvet
Authors: Makarushka Irena
Published: August 2007

In his early writing on language, truth, and art, Nietzsche notes that art “treats illusion as illusion; therefore it does not wish to deceive; it is true.” Insofar as art is an illusion whose only truth is that it is illusion, art is only true as a lie. When the illusion of art is mistaken for truth, art is destroyed. Nietzsche's observations about the truth of a work of art are instructive when considering the questions raised by postmodern artworks such as Blue Velvet, a film written and directed by David Lynch.

As Lynch explores the consequences of mistaking illusion for truth in Blue Velvet, he offers a disquieting analysis of the American Dream, its icons, and the cultural idolatry that sustains it. With a degree of suspicion characteristic of postmodern interpretative strategies, Lynch examines the values that define the “American Way of Life” and provides evidence to challenge the truth claim of traditional notions of good and evil.
John Eliot and the Millennium*
Authors: Cogley Richard W.
Published: August 2007

In 1643, twelve years after his arrival in Massachusetts Bay, John Eliot (1604-90), the Roxbury clergyman better known as the “Apostle to the Indians,” began to learn an Algonquian dialect in preparation for missionary work. After three years of study, he started to preach to the Indians in the colony. He continued to labor among them until the late 1680's, when his infirmity no longer permitted him to leave Roxbury. Over the course of these forty years, he attracted some eleven hundred Indians to the Christian faith, established fourteen reservations (“praying towns”) for his proselytes, and produced for Indians' use a number of Algonquian language works, including a translation of the Bible.

During the past twenty-five years, Eliot's career has received considerable scholarly attention. In 1965 Alden Vaughan portrayed Eliot as a conscientious missionary whose objective was to spread “Christian civilization” among the Indians.
Lemuel Haynes and the Revolutionary Origins of Black Theology, 1776-1801
Authors: Saillant John
Published: August 2007

Lemuel Haynes was a black Congregationalist minister to mostly white churches in New England and New York between 1788 and his death in 1833. Abandoned as an infant, Haynes was reared as an indentured servant in a pious white Massachusetts family. He served in the American Revolution in 1774 and 1775 as a Minute Man and in 1776 as a soldier in the march to Fort Ticonderoga. In 1776, Haynes composed an essay, “Liberty Further Extended: Or Free Thoughts on the Illegality of Slave-keeping.” After the Revolution, he acquired a reputation among his white contemporaries as an inspiring preacher. In 1788, Haynes accepted a call to minister in Rutland, Vermont, where he served for thirty years before being dismissed, perhaps because he was a black man. While at Rutland, he published a number of essays and sermons, including in 1801The Nature and Importance of True Republicanismand in 1806Universal Salvation. Universal Salvationultimately appeared in seventy editions, fifty-four of them within Haynes's lifetime.
Mary Lyon, the Founding of Mount Holyoke College, and the Cultural Revival of Jonathan Edwards
Authors: Conforti Joseph
Published: August 2007

Recent studies of the Second Great Awakening have stressed the strong appeal of evangelical religion to female worshippers. The revival has been portrayed as a “women's awakening” that nurtured “bonds of womanhood,” promoted female benevolence, and shaped antebellum canons of domesticity. Mary Lyon (1797-1849) and the founding of Mount Holyoke Seminary, which opened in 1837, have not gone unnoticed by historians of a women's awakening. In a follow-up essay to her important study of Catherine Beecher, for example, Kathryn Kish Sklar established the educational significance of Mount Holyoke and situated Lyon's efforts in the context of the Second Great Awakening. Mount Holyoke's innovations included secure financial support funded by the evangelical community at large; a resultant low cost that enabled students from modest and even poor backgrounds to enroll; and an intellectually rigorous curriculum that eschewed “ornamentations” such as dancing and the cultivation of gentility.
“Spiritual Warfare”: Cultural Fundamentalism and the Equal Rights Amendment
Authors: Mathews Donald G.
Published: August 2007

The Equal Rights Amendment (ERA) to the U.S. Constitution was to have been the next prize for women after winning the vote in 1920. This agenda—first set in 1923—was not accepted by many women or most members of the U.S. Congress until 1972. During the long generation that separated the conception and birth of the ERA, there came also the gestation of modern feminism, which differed from the earlier suffragist ideology in its understanding of gender. Suffragists, for the most part, worked within traditional definitions, insisting that complex and vexing social issues required a woman's touch; women's uniquely gendered experiences should be added to those of men to solve modern problems.
From Spiritualism to Theosophy: “Uplifting” a Democratic Tradition
Authors: Prothero Stephen
Published: August 2007

The status reversal ritual that American religious historiography has undergone in the last two decades has done much to “mainstream” previously taboo topics within the field. Many religious groups once dismissed as odd and insignificant “cults” are now seen as “new religious movements” worthy of serious scrutiny. One subject that has benefited from this reversal of fortunes is theosophy. Thanks to the work of scholars such as Robert Ellwood and Carl Jackson, theosophists are now part of the story of American religion. Exactly what part they are to play in that story remains, however, unclear.
Vernacular American Landscape: Methodists, Camp Meetings, and Social Respectability
Authors: Robins Roger
Published: August 2007

In 1822, from his Conway home in the shadow of New Hampshire's White Mountains, one Dr. Porter surveyed the nation's religious landscape and prophesied, “in half a century there will be no Pagans, Jews, Mohammedans, Unitarians or Methodists.” The prophecy proved false on all counts, but it was most glaringly false in the case of the Methodists. In less than a decade, Porter's home state became the eighth to elect a Methodist governor. Should Porter have fled south into Massachusetts to escape the rising Methodist tide, he would only have been buying time. True, the citizens of Provincetown, Massachusetts, had, in 1795, razed a Methodist meetinghouse and tarred and feathered a Methodist in effigy. By 1851, however, the Methodists boasted a swelling Cape Cod membership, a majority of the church members on Martha's Vineyard, and a governor in the Massachusetts statehouse.
“Proclaiming Together”? Convergence and Divergence in Mainline and Evangelical Evangelism, 1945-1967
Authors: Berg Thomas C.
Published: August 2007

By now, it is a commonplace of the American religious scene that the majority of the nation's white Protestant Christians are split into “two parties.” The ideological dividing line runs between “mainline” denominations—Methodists, Presbyterians, Episcopalians—and a bevy of conservative denominations and groups, but it also cuts through the mainline itself, which contains a substantial contingent of conservatives.

Among the two parties' numerous disagreements, theological and political, few have run deeper and longer than their difference over the meaning and importance of evangelism, the activity of “proclaiming the gospel” to those outside the Christian community. Is the church's prime call in this regard to seek conversions to the Christian faith, or is it to show the love of Christ by working for charitable goals and social justice? A well-known 1973 study of Presbyterian clergy found that the greatest polarization between self-described “conservatives” and “liberals” came over the relative priority of evangelism and social action. Indeed, the fight over these goals was an important (though by no means the only) factor precipitating the “split” early in this century.
The Ideal of Professionalism and the White Southern Baptist Ministry, 1870-1920
Authors: Harvey Paul
Published: August 2007

In 1917, a Baptist minister in Henderson, North Carolina, wrote to a Southern Baptist Convention (SBC) worker of the frustrations pastors encountered in teaching their parishioners a “progressive” religious ethic appropriate for the age:

Nearly all of us are driven by the force of circumstances to be a bit more conservative than it is in our hearts to be. I am frank to say to you that I have found it out of the question to move people in the mass at all, unless you go with a slowness that sometimes seems painful; and I have settled down to the conviction that it is better to lead people slowly than not at all.
Gender and Religion in American Culture, 1870-1930
Authors: Hackett David G.
Published: August 2007

Since the early 1980's, advances in the study of gender in American history have come primarily through an unmasking of the assumptions of earlier studies. Some have questioned the explanatory power of the field's dominant interpretive paradigm, that of “women's sphere,” because this theoretical lens has often led historians to mistake what was said by and about women for their actual historical experience. Others have laid bare the earlier scholarship's assumption of universal gender definitions that do not take into account differences in women's roles based on race, class, or region. Additionally, several historians have begun to explore the influence of gender relations on the lives of men. As a result, we are beginning to get a picture of gender in American history that goes beyond the “women's sphere” experience of white, middle-class, northeastern women.
Religion and Culture in Tension: The Abortion Discourses of the U.S. Catholic Bishops and the Southern Baptist Convention
Authors: Dillon Michele
Published: August 2007

Sociologists increasingly emphasize the systemic openness of religious organizations to their environment. Mark Kowalewski argues that the Catholic church, for example, engages in a “limited accommodation” with the broader culture in order to “rein in the forces of change and to keep modernizing elements under the control of the existing power elite.” Others suggest that the church manages its multiple identities across diverse audiences by articulating culturally adaptive discourses. Nancy Ammerman documents the responsiveness of religious organizations to political currents by demonstrating how doctrinal and ideological upheavals within the Southern Baptist Convention during the 1980's resulted in a conservative resurgence within the organization and a new administration committed to taking an activist public stance on various sociomoral issues, including abortion.
The Spiritual Labour of John Barnard: An Eighteenth-Century Artisan Constructs His Piety
Authors: Seeman Erik R.
Published: August 2007

John Barnard (1654-1732) was a carpenter. Not only did this Bostonian build houses, but he also constructed, throughout his life, a spiritual edifice. As a carpenter, Barnard used the tools and materials available to him and, within the architectural conventions of his day, built homes according to his individual judgment as a craftsman. Similarly, though in a less self-conscious manner, Barnard fashioned a cosmology out of the varied building blocks available to him in the religious culture of colonial Boston: sermons, godly books, pious conversation, and prayer. As is evident from his 184-page spiritual journal kept between January 1716 and October 1719, Barnard was the active constructor of a personal piety.
In Memory of Cassie: Child Death and Religious Vision in American Women's Novels
Authors: Morey Ann-Janine
Published: August 2007

This article investigates the contribution of several twentieth-century women writers to the legacy of women's writing about child death and scriptural consolation. The suffering and death of children constitutes the most intractable of religious problems, and recent studies of parental grieving support women's literary treatment of child death. Thus, just as child death creates a unique religious space, it may also demand its own literary category and aesthetic. By considering the unique dimensions of parental grieving, and by looking at how Perri Klass, Toni Morrison, and Harriette Arnow handle this subject, it is possible to gain fresh literary perspective on the fiction of nineteenth-century American women, many of whom also addressed the problem of child death and scriptural consolation. Women writers create children who are more than literary or symbolic commodities, and, in so doing, these writers challenge us to reevaluate scriptural and social perspectives on child death.
Staking the Monster: A Politics of Remonstrance
Authors: Ingebretsen Edward J.
Published: August 2007

Monster, you are an abomination. I love you.

Marquis de Sade,Juliette

Perversion is not an innate desire … but an identity and a category which is socially produced.

Jeffrey Dollimore,Sexual Dissidence

Some years ago I asked in an examination paper … “why were heretics persecuted in the thirteenth Century?” The question was very popular and the answer, with great confidence and near unanimity, “because there were so many of them.”

R. I. Moore,The Formation of a Persecuting Society

A social order reveals the limits of its imagination in two particular ways. The first is in the methods of fear by which it constructs the unspeakable (the “monstrous” or the “inhuman”) as symbolic center of social energy. The second is in the means, legal and extralegal, then used to repudiate and silence that energy.
With Bible in One Hand and Battle-Axe in the Other: Carry A. Nation as Religious Performer and Self-Promoter
Authors: Carver Frances Grace
Published: August 2007

Why do high school history books mention Carry Nation and not other women (and there were many) who marched into saloons with hatchets, pokers, Bibles, and off-key accordians? And why is it that these history textbooks caricature her as a masculinized and menopausal megalomaniac rather than as a religiously inspired reformer who gave voice to the hopes of thousands of people longing for an alcohol-free promised land? The answer to the first question lies in Nation's own genius at self-promotion and her remarkably media-genic personality. She had undeniable charisma and a certain brilliance in making the most out of it. The answer to the second question lies in the even greater success of entrepreneurs who manipulated her public appeal to their own profit-making advantage by luridly packaging her personality and Crusade with brassy embellishments and blatant untruths. The commercial culture she sought to manipulate, in the end, got the best of her: retailers, reporters, and her so-called managers twisted her image to fit their own desires to turn a quick profit.
Liberators for Colonial Anáhuac: A Rumination on North American Civil Religions
Authors: Walker Randi Jones
Published: August 2007

Behold here the motives of that mysterious likeness which give merit to a comparison with Jesus in the work the Supreme Author confided to [Hidalgo]: to save the American people, the continent of Anáhuac!

So spoke Padre Antonio Jose Martinez in 1832 in praise of Miguel Hidalgo on the tenth anniversary of the independence of the Republic of Mexico. That same year, Francis Gray extolled George Washington, the hero of another independence movement. Washington was the “Special instrument of divine providence for working out our political salvation, the cloud by day and pillar of fire by night which led us out of bondage.” Two new North American nations attempted to create a national identity and a useable mythology, side by side, if independent of each other. In this essay, I present a North American view of what could loosely be called civil religion.
Counterculture and Mission: Jews for Jesus and the Vietnam Era Missionary Campaigns, 1970-1975
Authors: Ariel Yaakov
Published: August 2007

In the early 1970's, Americans noticed a striking group of people: young men and women who stood in crowded city areas, wearing T-shirts with the motto “Jews for Jesus” and distributing leaflets calling upon Jews to embrace Jesus as their savior. These people made such a strong impression and attracted so much attention that, in the eyes of many, Jews for Jesus became associated with all attempts to evangelize Jews in America, as well as becoming one of the better known groups among the Jesus Movement. Directing its attention to members of the new counterculture and adapting to the young people's style and manners, Jews for Jesus differed sharply from evangelizing organizations of the earlier period. Whereas the older generation of missionaries strictly adhered to mid-century norms of conservative evangelical propriety, the new organization believed that its more daring approach would prove more effective with the younger generation and would eventually gain evangelical approval.
The Difference Difference Makes: Justine Wise Polier and Religious Matching in Twentieth-Century Child Adoption
Authors: Herman Ellen
Published: August 2007

During much of the twentieth Century, adoption has relied on the paradoxical theory that differences are managed best by denying their existence. According to the “matching” paradigm that has governed modern adoption, adults who acquire children born to others must look, feel, and behave as if they had given birth themselves. In spite of intensive efforts to erase distinction, distinction endures as an obvious characteristic of kinship outside of blood. The fact that adoption is a different way to make a family has profoundly shaped popular attitudes and professional policies. The fact that adoptive families are “made up” is surely one of the most interesting and important things about how such families come to be.
Holy Martin: The Overlooked Canonization of Dr. Martin Luther King, Jr.
Authors: Hoffman Scott W.
Published: August 2007

Martin Luther King, Jr., gazes serenely, almost expressionless, in a somber suit and tie before a backdrop of prison bars. Around his neck hangs a booking number, “7089.” Around his head is a brilliant golden halo. The picture is not a mug shot but an icon in the Byzantine tradition. It is, as its Greek inscription says, “Holy Martin.” St. Martin Luther King.

This icon is a popular piece of merchandise for a mail-order Company in Vermont. Each January, just before King's birthday they receive a flood of Orders. This phenomenon is an enigma, the fountainhead for a flood of questions. How can a black Baptist minister become the subject of a popular icon? What in American society and culture fostered its creation? Who invokes this great civil rights leader as a saint? But the most basic question is, how can Martin Luther King be considered a saint in the first place? Was it simply because he was slain for the cause of civil rights? Others died for the cause, and there are no icons of them.
Calcitonin Gene-Related Peptide Expression in Sepsis: Postulation of Microbial Infection-Specific Response Elements within the Calcitonin I Gene Promoter
Authors: Domenech Vivian Suarez , Nylen Eric S. , White Jon C. , Snider Richard H. , Becker Kenneth L. , Landmann Regine , Müller Beat
Published: August 2007

Background

Recently, we reported an unexpected ubiquitous expression of calcitonin (CT)-mRNA in a hamster peritonitis model of sepsis. Using this animal model, we undertook a study to further investigate the pattern of expression of the calcitonin I ( CALC-I) gene and CT gene-related peptide (CGRP)-mRNA in sepsis.

Methods

Live Escherichia coli impregnated in agar pellets were implanted in the peritoneal cavities of hamsters. Twelve hours after sepsis induction, the septic and healthy control animals were sacrificed and tissues and peritoneal macrophages were collected. CGRP-mRNA content was evaluated by reverse transcription polymerase chain reaction (RT-PCR), quantitated by the Taq-Man technique, and compared with the mRNA expression of CT, tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6). The 5′ untranslated regions of the mRNA and potential alternative splicing sites were identified by 5′ rapid amplification of cDNA ends.

Results

We found a tissue-wide, ubiquitous and uniform expression of CGRP-mRNA in all septic tissues examined. CGRP-mRNA was detectable by RT-PCR in various extraneuronal and extrathyroidal septic tissues, but not in healthy control tissues. As found for CT-mRNA in our earlier studies, CGRP-mRNA seemed to be more specifically up-regulated as compared with other classical cytokines (ie, IL-6 and TNF-α). Importantly, the 5′ untranslated sequence in control and septic thyroid was similar to the sequence obtained from septic spleen.

Conclusions

We postulate the presence of microbial infection-specific response elements in the CALC-I gene promotor, which, upon a specific stimulus, override the tissue-selective expression pattern. This new form of endocrine plasticity may be of importance in the response to systemic inflammation.
Fenamates Stimulate BKCa Channel Activity in the Human Osteoblast-Like MG-63 Cells
Authors: Wu Sheng-Nan , Jan Chung-Ren , Chiang Hung-Ting
Published: August 2007

Background

The fenamates, a family of nonsteroidal anti-inflammatory drugs that are derivatives of N-phenylanthranilic acid, are the inhibitors of cyclo-oxygenase. The ionic mechanism of actions of these compounds in osteoblasts is not well understood.

Methods

The effects of the fenamates on ionic currents were investigated in a human osteoblast-like cell line (MG-63) with the aid of the whole-cell and inside-out configurations of the patch-clamp technique.

Results

In MG-63 cells, niflumic acid and meclofenamic acid increased K+outward currents ( IK). The niflumic acid-stimulated IKwas reversed by subsequent application of iberiotoxin or paxilline, yet not by that of glibenclamide or apamin. In the inside-out configuration, niflumic acid (30 μmol/L) added to the bath did not modify single-channel conductance but increased the activity of large-conductance Ca2+-activated K+(BKCa) channels. The EC50values for niflumic acid- and meclofenamic acid-induced channel activity were 22 and 24 μmol/L, respectively. Niflumic acid (30 μmol/L) and meclofenamic acid (30 μmol/L) shifted the activation curve of BKCachannels to less positive membrane potentials. Membrane stretch potentiated niflumic acid-stimulated channel activity. The rank order of potency for the activation of BKCachannels in these cells was niflumic acid = meclofenamic acid > tolfenamic acid > flufenamic acid > nimesulide. Evans blue and nordihydroguaiaretic acid increased channel activity; however, indomethacin, piroxicam, and NS-398 had no effect on it.

Conclusions

The fenamates can stimulate BKCachannel activity in a manner that seems to be independent of the action of these drugs on the prostaglandin pathway. The activation of the BKCachannel may hyperpolarize the osteoblast, thereby modulating osteoblastic function.
Prevention of Morphological Changes in Alginate Microcapsules for Islet Xenotransplantation
Authors: Hobbs Hasan A. , Kendall William F. , Darrabie Marcus , Opara Emmanuel C.
Published: August 2007

Background

Alginate microcapsule swelling, which occurs as a result of increased hydrophilicity owing to the Ca++ that remains after rapid chelation of the inner alginate core, is a problem in encapsulation. We have previously shown that exchange of the residual divalent Ca++ with the monovalent Na+ through the use of 6 mmol/L Na2SO4 decreases swelling in chelated alginate-polylysine-alginate microcapsules, and this process enhances their durability. The purpose of the present study was to examine the morphology of Na2SO4-treated microcapsules in long-term incubation with the use of serum-supplemented culture medium.

Methods

Spherical beads of purified alginate (3%) that were gelled with 1.1% CaCl2 were first coated with polylysine, and then with 0.24% alginate. After rapid chelation of the inner alginate core with 55 mmol/L sodium citrate, the capsules were either incubated for 30 minutes in 6 mmol/L Na2SO4 or left untreated (control). Each group of capsules was then placed in a flask containing Ham's culture medium supplemented with 20% porcine serum and incubated at 37°C.

Results

The diameters of Na2SO4-treated capsules only increased modestly from a mean±SD of 635±22.08 to 684.53±17.86 μm ( P <0.0001) by day 7, with no further increases thereafter. In contrast, control capsules showed a steady increase in their mean diameters, which changed from 639.55±21.44 to 735.48±108.85 μm ( P<0.0001) by day 66. In addition, whereas treated capsules remained spherical, control capsules showed progressive polymorphism.

Conclusion

We have developed a new method of making more durable and stable microcapsules that can be used for islet cell xenotransplantation.
Vascular Expression of Integrin-Associated Protein and Thrombospondin Increase after Mechanical Injury
Authors: Sajid Mansoor , Hu Zhaoyong , Guo Huiping , Li Husong , Stouffer George A.
Published: August 2007

Background

Integrin-associated protein (IAP) is a thrombospondin (TSP)-binding, Gi protein-coupled cell surface receptor. The vascular function of IAP has not been defined, and it is not known whether TSP and IAP are expressed at the same time in injured arteries.

Methods

Left brachial arteries of baboons were injured using balloon withdrawal technique. Arteries were harvested 1 week after injury, and immunohistochemistry and in situ hybridization were performed using standard techniques. Uninjured right brachial arteries served as a control. Proliferation studies were performed using cultured human aortic smooth muscle cells (SMC).

Results

We found significant IAP expression in the media and neointima 7 days after injury using BRIC-126, an immunoglobulin (Ig) G2b monoclonal antibody that recognizes IAP with high specificity. In contrast, IAP staining in the uninjured vessel was only observed in the endothelium. Concurrent with IAP expression, TSP mRNA and protein expression in the neointima and media was enhanced 1 week after injury. In cultured SMC, activation of IAP was sufficient to elicit a proliferative response. TSP-induced proliferation was inhibited by antibodies that block TSP binding to IAP and mimicked by 4N1K, a 10-amino acid peptide derived from the IAP binding site within the carboxyl terminus of TSP.

Conclusions

Vascular expression of IAP and TSP increased after mechanical injury and activation of IAP elicited a proliferative response in cultured SMC. These findings support the hypothesis that IAP participates in vascular healing responses.
Magnitude of Peroxisome Proliferator-Activated Receptor-γ Activation is Associated with Important and Seemingly opposite Biological Responses in Breast Cancer Cells
Authors: Clay Carl E. , Namen Andrew M. , Atsumi Gen-ichi , Trimboli Anthony J. , Fonteh Alfred N. , High Kevin P. , Chilton Floyd H.
Published: August 2007

Background

The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) has become a potential target for the prevention and treatment of breast cancer. However, recent in vitro and in vivo studies have raised the question of whether activation of PPARγ leads to the promotion or reduction of tumor formation. Studies using several cancer cell lines, animal models, and a variety of PPARγ agonists have shown discordant results, including changes in cellular proliferation, differentiation, and apoptosis of cancer cells and tumors.

Methods

We studied the effects of low-, moderate-, and high-dose treatment of the PPARγ ligands 15-deoxy-Δ12,14 prostaglandin J2 (15dPGJ2) and troglitazone (TGZ) on parameters of cell growth, differentiation, and apoptosis in the epithelial breast cancer cell line MDA-MB-231.

Results

The biologic effects of these compounds depend largely on ligand concentration and the degree of PPARγ activation. For example, low concentrations of 15dPGJ2 (<2.5 μM) and TGZ (<5 μM) increased cellular proliferation, but concentrations of 15dPGJ2 >10 μM and of TGZ at 100 μM blocked cell growth. TGZ (100 μM) slowed cell cycle progression, and 15dPGJ2 (10 μM) caused an S-phase arrest in the cell cycle and induced morphological characteristics consistent with apoptosis. Expression of CD36, a marker of differentiation in these cells, was induced by 2.5 μM 15dPGJ2 or 5 to 100 μM TGZ. However, higher concentrations of 15dPGJ2 did not alter CD36 expression. Transcriptional activation studies demonstrated that 15dPGJ2 is a more potent PPARγ ligand than TGZ. Regardless of the ligand used, though, low transcriptional activation correlated with an increased cellular proliferation, whereas higher levels of activation correlated with cell cycle arrest and apoptosis.

Conclusions

PPARγ activation induces several important and seemingly opposite changes in neoplastic cells, depending on the magnitude of PPARγ activation. These data may explain, at least in part, some of the discordant results previously reported.
Obesity is Associated with Impaired Ventricular Protein Kinase C-MAP Kinase Signaling and Altered ANP mRNA Expression in the Heart of Adult Zucker Rats
Authors: Morabito Dominique , Vallotton Michel B. , Lang Ursula
Published: August 2007

Background

In the obesity model of the Zucker rat, myocardial protein kinase C (PKC) activation by phorbol ester is impaired. The influence of obesity on myocardial cell signaling was investigated by studying the activation of PKC isozymes and MAP kinases (MAPK) p38 and p42/44 as well as the induction of ANP mRNA.

Methods

Isolated hearts obtained from 17-week-old lean and obese Zucker rats were perfused with 200 nM phorbol 12-myristate 13-acetate (PMA) at different time periods. Immunodetectable PKC isozymes, phosphorylated-MAPK, and ANP mRNA were determined by Western and Northern blots, respectively.

Results

PMA promoted a marked transient translocation of ventricular PKCα from the cytosol to the membranes within 10 minutes in lean rats, whereas it had a much weaker effect in obese rats. Moreover, PMA induced a significant activation of PKCΔ in lean but not in obese rat hearts. After PKC activation, increases in phosphorylation levels of myocardial p38 and p42 MAPK were approximately 3-fold higher in lean rats than in obese animals. Concerning the induction of ANP, PMA transiently tripled ANP mRNA within 60 minutes in lean but not in obese rats.

Conclusions

In the genetically obese Zucker rat, the myocardial signal transduction cascade PKC-MAPK-ANP mRNA seems to be markedly impaired. It can be speculated that this abnormal cardiac cell signaling in obese rats reflects an early phase in the cardiac pathogenesis accompanying obesity.
Basal and Post-Methionine Serum Homocysteine and Lipoprotein Abnormalities in Patients with Chronic Liver Disease
Authors: Ben-Ari Ziv , Tur-Kaspa Ran , Schafer Zehava , Baruch Yaacov , Sulkes Jacqueline , Atzmon Orna , Greenberg Avital , Levi Nurit , Fainaru Menahem
Published: August 2007

Background

Lipoprotein abnormalities are commonly found in chronic liver diseases (CLDs), particularly hypercholesterolemia in primary biliary cirrhosis (PBC). However, affected patients may not be at increased risk of coronary heart disease. Cirrhotic patients display impaired methionine clearance, and an increased level of homocysteine, a methionine metabolite, is an independent risk factor for coronary heart disease. Thus, we hypothesized that the low risk of coronary heart disease in patients with CLD may be related to low serum levels of homocysteine. The aim of this study was to test this hypothesis after methionine load and to describe the serum lipoprotein profile in patients with PBC and in patients with hepatocellular liver disease.

Methods

Fifteen female patients (mean age, 58.2±11.7 years) with PBC, 15 female patients (mean age, 54.5 ± 9.6 years) with other causes of CLD, and 15 healthy sex- and age-matched controls were given L-methionine (50 mg/kg of ideal body weight). Basal fasting serum homocysteine level and 2, 4, and 6 hours of post-methionine load were determined using high-performance liquid chromatography with a fluorometric detector. Levels of fasting serum cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein (a) (Lp(a)), and apoprotein B were also determined.

Results

Results showed that mean basal and post-methionine load (6 hours) serum homocysteine levels were statistically significantly higher in the patients with PBC and with CLD than in the control group ( P=0.04) and that levels of serum cholesterol, LDL, HDL, and apoprotein B were significantly higher in the PBC patients than in the other two groups ( P≤0.05). There was no correlation between any of these parameters and the severity of liver disease. Serum HDL was significantly lower in the CLD group ( P≤0.05) and correlated with severity of liver disease. There was no significant difference in serum cholesterol, LDL, or apoprotein B between the CLD group and the controls. Serum triglyceride and Lp(a) levels were similar for all three groups.

Conclusions

In contrast to previous reports, the site of the methionine metabolic impairment was found to be below the homocysteine synthesis level. For most patients with CLD, factors other than serum homocysteine or Lp(a) are responsible for the reduction in the risk of coronary heart disease. Further studies with larger samples are needed.
Effect of Dexamethasone on TSH Secretion Induced by TRH in Human Obesity
Authors: Coiro Vittorio , Volpi Riccardo , Capretti Luigi , Speroni Guglielmina , Pilla Silvia , Cataldo Simona , Bianconcini Michele , Bazzani Emanuele , Chiodera Paolo
Published: August 2007

Background

The presence of an abnormally high thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) makes it difficult to distinguish some euthyroid obese subjects from subclinically hypothyroid obese patients. Here, we examine whether such distinction may be achieved after treatment with glucocorticoids, which inhibit TSH secretion at the hypothalamic-pituitary level.

Methods

TRH tests (200 μg as an intravenous bolus injection) were performed in 30 age- and weight-matched, obese, but otherwise healthy, men. All subjects were tested again with TRH after treatment with dexamethasone (dex) (2 mg/d in four divided doses orally for 3 days).

Results

In all subjects, total thyroxine and triiodothyronine concentrations were in the normal range. According to basal and TRH-stimulated serum thyrotropin (TSH) levels, subjects were divided into the following three groups: group I (n=10), euthyroid subjects; group II (n=10), euthyroid subjects with normal basal but abnormally elevated TSH responses to TRH; group III (n=10), subjects with elevated basal and TRH-induced TSH levels (subclinical hypothyroidism). Basal TSH levels were 1.8±0.4 mU/L in group I, 1.7±0.3 in group II, and 6.0±0.7 in group III. In both groups II and III, TRH-induced TSH increments were above the normal range (maximal increment>15 mU/L) and were significantly higher than in group I. After the second treatment with TRH, pretreatment with dex significantly decreased both basal TSH levels and peak TSH responses to TRH in all groups. However, a striking percentage decrease (>50%) in TRH-induced peak TSH responses was observed in euthyroid obese subjects of groups I and II, whereas hypothyroid subjects of group III showed only a slight decrement (<25%).

Conclusions

The sensitivity of the TSH secretory system to glucocorticoid inhibitory action is preserved in obese subjects with abnormally elevated TSH response to TRH, but not in subclinically hypothyroid obese patients. The TRH plus dex test might be useful in future studies to understand the mechanisms underlying alterations in TSH secretion in obesity.
Inhibition of L-Type Ca2+ Channel Current in Xenopus Oocytes by Amiodarone
Authors: Ding Shulan , Chen Fuhua , Klitzner Thomas S. , Wetzel Glenn T.
Published: August 2007

Background

Although amiodarone has been referred to as a class III antiarrhythmic agent, it also possesses electrophysiologic characteristics of the three other classes (classes I and IV and minor class II effects). Previous studies have demonstrated that amiodarone inhibits Ca2+ channel current in intact cardiac myocytes. However, it is not clear whether this response reflects a pure class IV effect (direct Ca2+ channel inhibition) or a class II effect (β-adrenergic receptor blockade) of amiodarone.

Methods

In the current study, the effects of amiodarone on Ca2+ current were studied in the absence of sympathetic regulation using a Xenopus oocyte expression system. The L-type Ca2+ channel α1C subunit was coexpressed with the α2Δ and β2a subunits in enzymatically digested Xenopus oocytes. Ca2+ currents were recorded using the cut-open oocyte preparation.

Results

We found that perfusion of 10 μM isoproterenol produced no significant change in peak Ca2+ current (from 223±33 to 210±29 nA, mean±SEM, n=5, P=not significant), indicating the absence of a functional stimulatory sympathetic signal pathway in these oocytes. After 10 minutes of exposure to 10 μM amiodarone, Ca2+ current amplitude was significantly decreased from 174±33 to 100±26 nA (n=8, P<0.01; control group: 220±33 to 212±29 nA, n=5, P=not significant). These effects were similar to those of 10 μM nifedipine (201±48 to 108±48 nA, n=6, P<0.05), a typical Ca2+ channel blocker. On the other hand, neither amiodarone nor nifedipine significantly altered the Ca2+ current activation or inactivation kinetics.

Conclusions

These results demonstrate that amiodarone inhibits Ca2+ current in the absence of a functional intrinsic β-adrenergic stimulatory system and, therefore, represents a true class IV effect.
Monocyte Chemoattractant Protein-1 and Interleukin-8 are Increased in Bronchopulmonary Dysplasia: Relation to Isolation of Ureaplasma Urealyticum
Authors: Baier John R. , Loggins John , Kruger Thomas E.
Published: August 2007

Background

An exaggerated inflammatory response occurs in infants who subsequently develop bronchopulmonary dysplasia (BPD). Ureaplasma urealyticum (Uu) is frequently isolated from cultures of tracheal secretions obtained from very low birth weight infants and is associated with an increased risk of BPD.

Methods

We examined the relationships between isolation of genital mycoplasmas, tracheal aspirate (TA) interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) concentrations and the development of BPD. Serial TAs were obtained prospectively from 35 very low birth weight infants, and IL-8 and MCP-1 concentrations were determined by enzyme-linked immunoadsorbent assay. Tracheal cultures for bacteria and genital mycoplasmas were performed on aspirates obtained during the first 2 days of life.

Results

Infants who developed BPD (n=18) were less mature (25.2±0.2 vs 27.8±0.5 weeks; P <0.001), of lower birth weight (746±28 vs 1052±41 g; P <0.001), and more likely to have a positive tracheal culture for Uu (39% vs 6%; P=0.026) than those who did not develop BPD (n=17). Tracheal concentrations of IL-8 and MCP-1 were significantly increased in infants who developed BPD (IL-8: P=0.0001; MCP-1: P <0.001, analysis of variance) and correlated with duration of mechanical ventilation and oxygen treatment. Uu-positive infants had an increased incidence of BPD (88% in infants with Uu vs 42% in infants without Uu; P=0.020) and had TA concentrations of IL-8 and MCP-1 that were significantly increased compared with those of Uu-negative infants.

Conclusions

Increased TA concentrations of IL-8 and MCP-1 during the first 2 weeks of life are associated with the development of BPD. Recovery of Uu from TAs is associated with a more robust inflammatory reaction and an increased risk of BPD.
Disease Association, Origin, and Clinical Relevance of Autoantibodies to the Glycolytic Enzyme Enolase
Authors: Gitlits Veronika M. , Toh Ban-Hock , Sentry John W.
Published: August 2007

Serum autoantibodies to the glycolytic enzyme enolase have been reported in a diverse range of inflammatory, degenerative, and psychiatric disorders. Diseases in which these antibodies have been reported in high incidence include autoimmune polyglandular syndrome type 1 (80%, 35 of 44), primary (69%, 60 of 87), and secondary (58%, 14 of 24) membranous nephropathy, cancer-associated retinopathy (68.8%, 11 of 16), autoimmune hepatitis type 1 (60%, 12 of 20), mixed cryoglobulinemia with renal involvement (63.6%, seven of 11), cystoid macular edema (60%, six of 10), and endometriosis (50%, 21 of 41). In autoimmune polyglandular syndrome type 1 patients, all had chronic mucocutaneous candidiasis with demonstrated antibody reactivity to candida enolase, which is suggestive of cross reactivity or epitope mimicry. Formation of autoantibodies to enolase may be a normal process, with reported incidence in apparently healthy subjects ranging from 0% (zero of 91) to 11.7% (seven of 60). Nonetheless, we suggest that excessive production of these autoantibodies, which are generated as a consequence of uptake of enolase by antigen-presenting cells and subsequent B cell activation, can potentially initiate tissue injury as a result of immune complex deposition.
Association of Reactive Nitrogen Species Metabolites, Myeloperoxidase, and Airway Inflammation in Lung Transplants
Authors: de Andrade João A. , Christie Jason D. , Alexander C. Bruce , Young K. Randall , McGiffin David C. , Zorn George L. , Jackson Robert M.
Published: August 2007

Background

We have previously reported that patients who had single or double lung transplants had higher concentrations than controls of nitrite and nitrate, which are metabolites of reactive nitrogen species (RNS), in bronchoalveolar lavage fluid (BALF) and serum.

Methods

This study investigates implications of RNS metabolites as markers of airway inflammation in a distinct group of lung transplant patients (n=40). All patients underwent spirometry, routine surveillance transbronchial lung biopsies, and bronchoalveolar lavage as required by clinical protocol. Four normal controls also had bronchoscopy for measurement of BALF nitrite (NO2−) and nitrate (NO3−). BALF NO2− and NO3−, myeloperoxidase (MPO), protein, and urea were assayed. Total nitrite (NO2− plus enzymatically reduced NO3−) and urea were measured in serum.

Results

BALF RNS metabolites were mainly NO3−. Forced expiratory volume in 1 s (FEV1) obtained near bronchoscopy was compared with best postoperative FEV1. Total nitrite in transplant patients’ BALF and serum were 3.8±0.2 and 49±5 μM, respectively. Total nitrite in controls’ BALF and serum were 2.2±0.7 and 19±2 μM, respectively ( P<0.05 compared with transplant values). Serum total nitrite correlated (Pearson product moment) with percentage of neutrophils in BALF ( R=0.650, P<0.0001), MPO ( R=0.431, P=0.0055), change in FEV1 from baseline (ΔFEV1) ( R=-0.348, P=0.0298), and days after transplantation ( R=0.345, P=0.0294). None of the associated variables, airway inflammation (quantified as a score, “B”), ΔFEV1, serum, or BALF total nitrite, were explained by infection. Univariate analysis of airway inflammation in patients showed that it was associated with BALF neutrophils, ΔFEV1, and serum total nitrite.

Conclusions

Serum nitrite appears to reflect the degree of airway inflammation in this lung-transplant study group.
Unanticipated Favorable Effects of Correcting Iron Deficiency in Chronic Hemodialysis Patients
Authors: Pollak Victor E. , Lorch Jonathan A. , Means Robert T.
Published: August 2007

Background

Correction of anemia in hemodialysis patients is seldom completely attained, and the response of parameters other than hemoglobin concentration to anemia correction has not been evaluated in detail.

Methods

Laboratory parameters that suggest iron deficiency occurred in 10-15% of 206 recombinant human erythropoietin (rhEPO)-treated patients. Oral iron was given for 9 months and intravenous iron thereafter on a patient-specific basis when iron deficiency was evident. Eighty-seven hemodialysis patients with data for 12 months were followed for another 12 months. A computerized information system enabled data management and analysis.

Results

With oral iron, serum ferritin decreased ( P<0.001), indicating further iron depletion. With intravenous iron, hemoglobin increased, evidence of iron deficiency decreased, and less rhEPO was needed. Striking macrocytosis appeared. Serum albumin and serum creatinine/kg body weight (an index of muscle mass) increased, while blood pressure decreased. Data were reanalyzed in four mean corpuscular volume (MCV) quartiles and two ferritin subsets at study onset. Iron deficient erythropoiesis (low MCV, mean corpuscular hemoglobin [MCH], and transferrin saturation) was striking in quartile 1; low ferritin was prevalent in all quartiles. With intravenous iron, hemoglobin increased only in quartile 1, the quartile with the greatest decrease (52%) in rhEPO dose. MCV increased in all quartiles ( P<0.001). Serum albumin increased in all MCV quartiles and both ferritin subsets, but significant creatinine/kg increase and blood pressure decrease occurred only in the low-ferritin subset.

Conclusions

Macrocytosis occurred with intravenous iron replacement. The universal MCV increase suggests unrecognized, inadequately treated, folic acid deficiency unmasked by an adequate iron supply. There was also improved well being. Effects were most clearly evident in patients with deficient iron stores.