Firing Up the Crucible with Senator Lee Metcalf & Governor Forrest Anderson -- Judge Gordon Bennett in “The Crucible of Change”

During the lead-up to Montana second progressive era, Lee Metcalf and Forrest Anderson, along with others, kept the progressive flame lit in Montana. Metcalf’s political history is replete with close electoral wins because of his commitment to progressive ideals when the times were not always politically favorable for that. As State Legislator, MT Supreme Court Justice, Congressman and eventually as US Senator, Lee won races by as little as 55 votes because he stuck to his guns as a progressive. In Forrest Anderson’s career as a County Attorney, State Legislator, MT Supreme Court Justice and 12 years as MT Attorney General he was respected as a pragmatic practitioner of politics. But during that entire career leading up to his election as Governor, Forrest Anderson was also a stalwart supporter of the progressive agenda exemplified by FDR and the New Deal, which brought folks out of the Great Depression that was brought on by the bad policies of the GOP and big business. As MT’s second progressive period began in 1965, the first important election was Senator Metcalf’s successful re-election battle in 1966 with the sitting MT Governor, Tim Babcock. And the progressive express was really ignited by the election of Forrest Anderson as Governor in 1968 after 16 years of Republican Governors in MT. Gordon Bennett played a rather unique role, being a confidant of Metcalf and Anderson, both who respected his wide and varied experience, his intellect, and his roots in progressivism beginning with his formative years in the Red Corner of NE Montana. Working with Senator Metcalf and his team, including Brit Englund, Vic Reinemer, Peggy McLaughlin, Betty Davis and Jack Condon among others, Bennett helped shape the progressive message both in Washington DC and MT. Progressive labor and farm organizations, part of the progressive coalition, benefitted from Bennett’s advice and counsel and aided the Senator in his career including the huge challenge of having a sitting popular governor run against him for the Senate in 1966. Metcalf’s noted intern program produced a cadre of progressive leaders in Montana over the years. Most notably, Ron Richards transitioned from Metcalf Intern to Executive Secretary of the Montana Democratic Party (MDP) and assisted, along with Bennett, in the 1966 Metcalf-Babcock race in a big way. As Executive Secretary Richards was critical to the success of the MDP as a platform for Forrest Anderson’s general election run and win in 1968. After Forrest’s gubernatorial election, Richards became Executive Assistant (now called Chief of Staff) for Governor Anderson and also for Governor Thomas Judge. The Metcalf progressive strain, exemplified by many including Richards and Bennett, permeated Democratic politics during the second progressive era. So, too, did the coalition that supported Metcalf and his policies. The progressivism of the period of “In the Crucible of Change” was fired up by Lee Metcalf, Forrest Anderson and their supporters and coalitions, and Gordon Bennett was in the center of all of that, helping fire up the crucible, setting the stage for many policy advancements in both Washington DC and Montana. Gordon Bennett’s important role in the 1966 re-election of Senator Lee Metcalf and the 1968 election of Governor Forrest Anderson, as well as his wide experience in government and politics of that time allows him to provide us with an insider’s personal perspective of those races and other events at the beginning of the period of progressive change being documented “In the Crucible of Change,” as well as his personal insights into the larger political/policy picture of Montana. Gordon Bennett, a major and formative player “In the Crucible of Change,” was born in the far northeast town of Scobey, MT in 1922. He attended school in Scobey through the eighth grade and graduated from Helena High School. After attending Carroll College for two years, he received his BA in economics from Carleton College in Northfield, MN. During a brief stint on the east coast, his daily reading of the New York Times (“best newspaper in the world at that time … and now”) inspired him to pursue a career in journalism. He received his MA in Journalism from the University of Missouri and entered the field. As a reporter for the Great Falls Tribune under the ownership and management of the Warden Family, he observed and competed with the rigid control of Montana’s press by the Anaconda Company (the Great Falls Tribune was the only large newspaper in Montana NOT owned by ACM). Following his intellectual curiosity and his philosophical bend, he attended a number of Farm-Labor Institutes which he credits with motivating him to pursue solutions to economic and social woes through the law. In 1956, at the age of 34, he received his Juris Doctorate degree from the Georgetown University Law Center in Washington, DC. Bennett’s varied career included eighteen years as a farmer, four years in the US Army during WWII (1942-46), two years as Assistant MT Attorney General (1957-59) with Forrest Anderson, three years in private practice in Glasgow (1959-61), two years as Associate Solicitor in the Department of Interior in Washington, DC (1961-62), and private law practice in Helena from 1962 to 1969. While in Helena he was an unsuccessful candidate for the Montana Supreme Court (1962) and cemented his previous relationships with Attorney General Forrest Anderson and US Senator Lee Metcalf. Bennett modestly refuses to accept the title of Campaign Manager for either Lee Metcalf (1966 re-election over the challenger, MT Republican Governor Tim Babcock) or Forrest Anderson (his 1968 election as Governor), saying that “they ran their campaigns … we were only there to help.” But he has been generally recognized as having filled that critical role in both of those critical elections. After Governor Anderson’s election in 1968, Bennett was appointed Director of the MT Unemployment Compensation Commission, a position from where he could be a close advisor and confidant of the new Governor. In 1971, Governor Anderson appointed him Judge in the most important jurisdiction in Montana, the 1st Judicial District in Helena, a position he held for seventeen years (1971-88). Upon stepping down from his judgeship, for twenty years (1988-2008) he was a law instructor, mediator and arbitrator. He currently resides in Helena with his wife, Norma Tirrell, former newspaper reporter and researcher/writer. Bennett has two adult children and four grandchildren.

The etiology of liver damage imparts cytokines transforming growth factor beta1 or interleukin-13 as driving forces in fibrogenesis

It is unknown whether transforming growth factor beta1 (TGF-beta1) signaling uniformly participates in fibrogenic chronic liver diseases, irrespective of the underlying origin, or if other cytokines such as interleukin (IL)-13 share in fibrogenesis (e.g., due to regulatory effects on type I pro-collagen expression). TGF-beta1 signaling events were scored in 396 liver tissue samples from patients with diverse chronic liver diseases, including hepatitis B virus (HBV), hepatitis C virus (HCV), Schistosoma japonicum infection, and steatosis/steatohepatitis. Phospho-Smad2 staining correlated significantly with fibrotic stage in patients with HBV infection (n = 112, P < 0.001) and steatosis/steatohepatitis (n = 120, P < 0.01), but not in patients with HCV infection (n = 77, P > 0.05). In tissue with HBx protein expression, phospho-Smad2 was detectable, suggesting a functional link between viral protein expression and TGF-beta1 signaling. For IL-13, immunostaining correlated with fibrotic stage in patients with HCV infection and steatosis/steatohepatitis. IL-13 protein was more abundant in liver tissue lysates from three HCV patients compared with controls, as were IL-13 serum levels in 68 patients with chronic HCV infection compared with 20 healthy volunteers (72.87 +/- 26.38 versus 45.41 +/- 3.73, P < 0.001). Immunohistochemistry results suggest that IL-13-mediated liver fibrogenesis may take place in the absence of phospho-signal transducer and activator of transcription protein 6 signaling. In a subgroup of patients with advanced liver fibrosis (stage > or =3), neither TGF-beta nor IL-13 signaling was detectable. Conclusion: Depending on the cause of liver damage, a predominance of TGF-beta or IL-13 signaling is found. TGF-beta1 predominance is detected in HBV-related liver fibrogenesis and IL-13 predominance in chronic HCV infection. In some instances, the underlying fibrogenic mediator remains enigmatic.

The immunomodulatory sphingosine 1-phosphate analog FTY720 reduces lesion size and improves neurological outcome in a mouse model of cerebral ischemia

Cerebral ischemia is accompanied by fulminant cellular and humoral inflammatory changes in the brain which contribute to lesion development after stroke. A tight interplay between the brain and the peripheral immune system leads to a biphasic immune response to stroke consisting of an early activation of peripheral immune cells with massive production of proinflammatory cytokines followed by a systemic immunosuppression within days of cerebral ischemia that is characterized by massive immune cell loss in spleen and thymus. Recent work has documented the importance of T lymphocytes in the early exacerbation of ischemic injury. The lipid signaling mediator sphingosine 1-phosphate-derived stable analog FTY720 (fingolimod) acts as an immunosuppressant and induces lymphopenia by preventing the egress of lymphocytes, especially T cells, from lymph nodes. We found that treatment with FTY720 (1mg/kg) reduced lesion size and improved neurological function after experimental stroke in mice, decreased the numbers of infiltrating neutrophils, activated microglia/macrophages in the ischemic lesion and reduced immunohistochemical features of apoptotic cell death in the lesion.

Expression and Function of Siglec-8 in Human Eosinophils, Basophils, and Mast Cells

Siglec-8, the eighth member of the sialic acid-binding, immunoglobulin [Ig]-like lectin family, was initially discovered as a cell surface protein selectively expressed on human eosinophils. It is now know to also be expressed by mast cells and basophils. Siglec-8 engagement with specific antibodies causes apoptosis via caspase and mitochondrial-dependent pathways. For mast cells, inhibition of mediator release, but no apoptosis, is observed. Siglec-F is the closest mouse paralog to Siglec-8, and both selectively bind the sulfated glycan 6’-sulfo-sialyl Lewis X. Antibodies to Siglec-F reduce blood and tissue eosinophil numbers in vivo. This suggests that Siglec-8 may be a useful future therapeutic target for allergic and other eosinophilic disorders.

RhoH/TTF negatively regulates leukotriene production in neutrophils

Leukotriene B(4) (LTB(4)) is an important proinflammatory lipid mediator generated by neutrophils upon activation. GM-CSF stimulation is known to enhance agonist-mediated LTB(4) production of neutrophils within minutes, a process called "priming". In this study, we demonstrate that GM-CSF also limits the production of LTB(4) by neutrophils via a transcriptional mechanism at later time points. We identified hemopoietic-specific Ras homologous (RhoH)/translocation three four (TTF), which was induced following GM-CSF stimulation in neutrophils, as a key regulator in this process. Neutrophils derived from RhoH/TTF-deficient (Rhoh(-/-)) mice demonstrated increased LTB(4) production upon activation compared with normal mouse neutrophils. Moreover, neutrophils from cystic fibrosis patients expressed enhanced levels of RhoH/TTF and generated less LTB(4) upon activation compared with normal human neutrophils. Taken together, these data suggest that RhoH/TTF represents an inducible feedback inhibitor in neutrophils that is involved in the limitation of innate immune responses.

Immunohistochemical localization of RANK, RANKL and OPG in healthy and arthritic canine elbow joints

OBJECTIVE: To determine if the receptor activator of nuclear factor-kappaB-receptor activator of nuclear factor-kappaB ligand-osteoprotegerin (RANK-RANKL-OPG) system is active in bone remodeling in dogs and, if so, whether differences in expression of these mediators occur in healthy and arthritic joints. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Fragmented processus coronoidei (n=20) were surgically removed from dogs with elbow arthritis and 5 corresponding healthy samples from dogs euthanatized for reasons other than elbow joint disease. METHODS: Bright-field immunohistochemistry and high-resolution fluorescence microscopy were used to investigate the distribution of RANK, RANKL, and OPG in healthy and arthritic joints. RESULTS: All 3 molecules were identified by immunostaining of canine bone tissue. In elbow dysplasia, the number of RANK-positive osteoclasts was increased. In their vicinity, cells expressing RANKL, a mediator of osteoclast activation, were abundant whereas the number of osteoblasts having the potential to limit osteoclastogenesis and bone resorption via OPG was few. CONCLUSIONS: The RANK-RANKL-OPG system is active in bone remodeling in dogs. In elbow dysplasia, a surplus of molecules promoting osteoclastogenesis was evident and is indicative of an imbalance between the mediators regulating bone resorption and bone formation. Both OPG and neutralizing antibodies against RANKL have the potential to counterbalance bone resorption. CLINICAL RELEVANCE: Therapeutic use of neutralizing antibodies against RANKL to inhibit osteoclast activation warrants further investigation.

Toxic effects of brake wear particles on epithelial lung cells in vitro

ABSTRACT: BACKGROUND: Fine particulate matter originating from traffic correlates with increased morbidity and mortality. An important source of traffic particles is brake wear of cars which contributes up to 20% of the total traffic emissions. The aim of this study was to evaluate potential toxicological effects of human epithelial lung cells exposed to freshly generated brake wear particles. RESULTS: An exposure box was mounted around a car's braking system. Lung cells cultured at the air-liquid interface were then exposed to particles emitted from two typical braking behaviours ("full stop" and "normal deceleration"). The particle size distribution as well as the brake emission components like metals and carbons was measured on-line, and the particles deposited on grids for transmission electron microscopy were counted. The tight junction arrangement was observed by laser scanning microscopy. Cellular responses were assessed by measurement of lactate dehydrogenase (cytotoxicity), by investigating the production of reactive oxidative species and the release of the pro-inflammatory mediator interleukin-8. The tight junction protein occludin density decreased significantly (p < 0.05) with increasing concentrations of metals on the particles (iron, copper and manganese, which were all strongly correlated with each other). Occludin was also negatively correlated with the intensity of reactive oxidative species. The concentrations of interleukin-8 were significantly correlated with increasing organic carbon concentrations. No correlation was observed between occludin and interleukin-8, nor between reactive oxidative species and interleukin-8. CONCLUSION: These findings suggest that the metals on brake wear particles damage tight junctions with a mechanism involving oxidative stress. Brake wear particles also increase pro-inflammatory responses. However, this might be due to another mechanism than via oxidative stress.

Annexin-1 regulates macrophage IL-6 and TNF via glucocorticoid-induced leucine zipper

Annexin-1 (ANXA1) is a mediator of the anti-inflammatory actions of endogenous and exogenous glucocorticoids (GC). The mechanism of ANXA1 effects on cytokine production in macrophages is unknown and is here investigated in vivo and in vitro. In response to LPS administration, ANXA1(-/-) mice exhibited significantly increased serum IL-6 and TNF compared with wild-type (WT) controls. Similarly, LPS-induced IL-6 and TNF were significantly greater in ANXA1(-/-) than in WT peritoneal macrophages in vitro. In addition, deficiency of ANXA1 was associated with impairment of the inhibitory effects of dexamethasone (DEX) on LPS-induced IL-6 and TNF in macrophages. Increased LPS-induced cytokine expression in the absence of ANXA1 was accompanied by significantly increased LPS-induced activation of ERK and JNK MAPK and was abrogated by inhibition of either of these pathways. No differences in GC effects on MAPK or MAPK phosphatase 1 were observed in ANXA1(-/-) cells. In contrast, GC-induced expression of the regulatory protein GILZ was significantly reduced in ANXA1(-/-) cells by silencing of ANXA1 in WT cells and in macrophages of ANXA1(-/-) mice in vivo. GC-induced GILZ expression and GC inhibition of NF-kappaB activation were restored by expression of ANXA1 in ANXA1(-/-) cells, and GILZ overexpression in ANXA1(-/-) macrophages reduced ERK MAPK phosphorylation and restored sensitivity of cytokine expression and NF-kappaB activation to GC. These data confirm ANXA1 as a key inhibitor of macrophage cytokine expression and identify GILZ as a previously unrecognized mechanism of the anti-inflammatory effects of ANXA1.

René Sand (1877-1953) and His Contribution to International Social Work, IASSW-President 1946 – 1953

The extraordinary significance of the life and work of René Sand lies in his central position as a mediator, promoter and coordinator of social work on an increasingly international level during the interwar-period and it can hardly be overestimated. To approach the achievements of Sand’s life and work you have to work archaeologically as he does not seem to have left any traces in the literature on social history. In Germany, even within the field of social work his name is hardly known. His biographical sketch and his importance for the development of the profession of social work have fallen into oblivion. The situation is a little different in the French-speaking countries where a biography has been published (compare Anciaux 1988a, b, c) which contains a detailed record of Sand’s writings. Altogether this lack of interest is regrettable because it doesn’t consider that René Sand is exemplary and in some parts fundamental to the emergence of professional social work in the 1920s in Belgium and Europe. Professional social work was established by a consequent international orientation and an emancipation from neighbouring fields such as social medicine and hygiene. Therefore it is a rewarding task to draw attention to this pioneer of social work and make the public appreciate his work. I want to emphasize explicitly that in this portrait Sand’s achievements concerning social work will be the main focus, even if this is an inevitable reduction of his accomplishments in the field of medicine and social medicine.

René Sand (Belgium), President 1946 – 1953

The extraordinary significance of the life and work of René Sand lies in his central position as a mediator, promoter and coordinator of social work on an increasingly international level during the interwar-period and it can hardly be overestimated.

The Levy Runs Dry: A Legal and Economic Analysis of EU Private Copying Levies

This article provides a legal and economic analysis of private copying levies in the EU, against the background of the Copyright Directive (2001/29), a number of recent rulings by the European Court of Justice and the recommendations presented by mediator Vitorino earlier this year. It concludes that notwithstanding these rulings and recommendations, there remains a lack of concordance on the relevance of contractual stipulations and digital rights management technologies (DRM) for setting levies, and the concept of harm. While Mr Vitorino and AG Sharpston (in the Opinion preceding VG Wort v. Kyocera) use different lines of reasoning to argue that levies raised on authorised copies would lead to double payment, the Court of Justice’s decision in VG Wort v. Kyocera seems to conclude that such copies should nonetheless be levied. If levies are to provide fair compensation for harm resulting from acts of private copying, economic analysis suggests one should distinguish between various kinds of private copies and take account of the extent to which the value said copies have for consumers can be priced into the purchase. Given the availability of DRM (including technical protection measures), the possibility of such indirect appropriation leads to the conclusion that the harm from most kinds of private copies is de minimis and gives no cause for levies. The user value of copies from unauthorised sources (e.g. from torrent networks or cyber lockers), on the other hand, cannot be appropriated indirectly by rightholders. It is, however, an open question in references for preliminary rulings pending at the Court of Justice whether these copies are included in the scope of the private copying exception or limitation and can thus be levied for. If they are not, as currently happens in several EU Member States, legal and economic analysis leads to the conclusion that the scope of private copying acts giving rise to harm susceptible of justifying levies is gradually diminishing.

The impact of the achievement motive on athletic performance in adolescent football players

Researchers largely agree that there is a positive relationship between achievement motivation and athletic performance, which is why the achievement motive is viewed as a potential criterion for talent. However, the underlying mechanism behind this relationship remains unclear. In talent and performance models, main effect, mediator and moderator models have been suggested. A longitudinal study was carried out among 140 13-year-old football talents, using structural equation modelling to determine which model best explains how hope for success (HS) and fear of failure (FF), which are the aspects of the achievement motive, motor skills and abilities that affect performance. Over a period of half a year, HS can to some extent explain athletic performance, but this relationship is not mediated by the volume of training, sport-specific skills or abilities, nor is the achievement motive a moderating variable. Contrary to expectations, FF does not explain any part of performance. Aside from HS, however, motor abilities and in particular skills also predict a significant part of performance. The study confirms the widespread assumption that the development of athletic performance in football depends on multiple factors, and in particular that HS is worth watching in the medium term as a predictor of talent.

In vitro differentiation of near-unlimited numbers of functional mouse basophils using conditional Hoxb8

Background: Basophils constitute a rare leukocyte population known for their effector functions in inflammation and allergy, as well as more recently described immunoregulatory roles. Besides their low frequency, functional analysis of basophils is hindered by a short life span, inefficient ex vivo differentiation protocols, and lack of suitable cell models. A method to produce large quantities of basophils in vitro would facilitate basophil research and constitute a sought-after tool for diagnostic and drug testing purposes. Methods: A method is described to massively expand bone marrow–derived basophils in vitro. Myeloid progenitors are conditionally immortalized using Hoxb8 in the presence of interleukin-3 (IL-3) and outgrowing cell lines selected for their potential to differentiate into basophils upon shutdown of Hoxb8 expression. Results: IL-3-dependent, conditional Hoxb8-immortalized progenitor cell lines can be expanded and maintained in culture for prolonged periods. Upon shutdown of Hoxb8 expression, near-unlimited numbers of mature functional basophils can be differentiated in vitro within six days. The cells are end-differentiated and short-lived and express basophil-specific surface markers and proteases. Upon IgE- as well as C5a-mediated activation, differentiated basophils release granule enzymes and histamine and secrete Th2-type cytokines (IL-4, IL-13) and leukotriene C4. IL-3-deprivation induces apoptosis correlating with upregulation of the BH3-only proteins BCL-2-interacting mediator of cell death (BIM) and p53 upregulated modulator of apoptosis (PUMA) and downregulation of proviral integration site for Moloney murine leukemia virus 1 kinase (PIM-1). Conclusion: A novel method is presented to generate quantitative amounts of mouse basophils in vitro, which moreover allows genetic manipulation of conditionally immortalized progenitors. This approach may represent a useful alternative method to isolating primary basophils.

The potential association between gingival crevicular fluid inflammatory mediators and adverse pregnancy outcomes: a systematic review

OBJECTIVES The association between periodontal disease and adverse pregnancy outcomes (APO), primarily preterm birth (PTB), is still controversially discussed in the literature. Therefore, the aim of the present systematic review was to analyze the existing literature on the potential association between inflammatory mediators detected in gingival crevicular fluid (GCF) and APO. MATERIALS AND METHODS MEDLINE (PubMed) and EMBASE databases were searched for entries up to April 2012 and studies were selected by two independent reviewers. RESULTS The majority of the eight studies included confirmed a positive association between GCF mediators, such as interleukin-1β, prostaglandin E2, and tumor necrosis factor-alpha, and APO. Due to the heterogeneity and variability of the available studies, no meta-analysis could be performed. CONCLUSIONS A positive association between GCF inflammatory mediator levels and APO/PTB might be present but the results need to be considered with great caution because of the heterogeneity and variability among the studies. Further studies with an adequate number of patients allowing for an appropriate analysis are warranted to definitely confirm this association. CLINICAL RELEVANCE The present findings suggest that an association between GCF inflammatory mediator levels and APO might exist.

Avoidance goal pursuit depletes self-regulatory resources.

Objective Research on the strength model of self-regulation is burgeoning, but little empirical work has focused on the link between distinct types of daily goal pursuit and the depletion of self-regulatory resources. The authors conducted two studies on the link between avoidance goals and resource depletion. Method Study 1 (283 [228 female] Caucasians, ages 18–51) investigated the concurrent and longitudinal relations between avoidance goals and resource depletion over a 1-month period. Study 2 (132 [93 female] Caucasians, ages 18–49) investigated the concurrent and longitudinal relations between avoidance goals and resource depletion over a 1-month period and explored resource depletion as a mediator of the avoidance goal to subjective well-being relation. Results Studies 1 and 2 documented both a concurrent and a longitudinal negative relationship between avoidance goals and self-regulatory resources, and Study 2 additionally showed that self-regulatory resources mediate the negative link between avoidance goals and subjective well-being. Ancillary analyses demonstrated that the results observed in the two studies were independent of neuroticism. Conclusions These findings advance knowledge in both the resource depletion and avoidance goal literatures, and bolster the view that avoidance goal pursuit over time represents a self-regulatory vulnerability.