bluuebunny/crossref_metadata_2025 huggingface dataset:
Leaders and elites: portrayals of smoking in popular films: Table 1
Authors: Dozier D M , Lauzen M M , Day C A , Payne S M , Tafoya M R
Published: February 2005

Objective:To study frequency and traits of characters that smoke in films and to document on-screen consequences of tobacco use.

Design:This study conducted a content analysis of the top 100 grossing films in 2002, with a total global gross of US$12.4 billion.

Outcome measures:Three outcome measures were frequency of smoking incidents, traits of characters who smoke, and consequences of tobacco use.

Results:6% of characters smoked in 453 incidents, including 3% of children. In 92% of incidences, smoking had no consequences. The most frequent consequence was a verbal reprimand. Although tobacco is a leading cause of preventable deaths globally, only 0.4% of tobacco incidences resulted in death. No deaths were caused by disease. Characters who smoked tended to be major characters playing leadership roles. They tended to be from privileged elites: male, white, and mature.

Conclusions:Films portray characters that smoke as leaders from privileged elites, making smoking more attractive to audience members. Because 99.6% of characters suffer no life threatening consequences from smoking on screen, smokers seem invincible, belying tobacco’s role as a leading cause of preventable deaths.
Tobacco control implications of the first European product liability suit: Table 1
Authors: Hiilamo H T
Published: February 2005

Objective:To examine tobacco control implication of the first European product liability suit in Finland.

Methods:Systematic search of internal tobacco industry documents available on the internet and at the British American Tobacco Guildford Depository.

Results:Despite legal loss, the litigation contributed to subsequent tobacco control legislation in Finland. The proceedings revealed that the industry had concealed the health hazards of its products and, despite indisputable evidence, continued to deny them. The positions taken by the industry rocked its reliability as a social actor and thus weakened its chances of influencing tobacco policy. Despite fierce opposition from the tobacco industry, tobacco products were included in the product liability legislation, tobacco was entered on the Finnish list of carcinogens, and an extensive Tobacco Act was passed in Parliament.

Conclusions:Tobacco litigation might not stand alone as a tool for public health policymaking but it may well stimulate national debate over the role of smoking in society and influence the policy agenda.
Loaded wheel running and muscle adaptation in the mouse
Authors: Konhilas John P. , Widegren Ulrika , Allen David L. , Paul Angelika C. , Cleary Allison , Leinwand Leslie A.
Published: February 2005

Voluntary cage wheel exercise has been used extensively to determine the physiological adaptation of cardiac and skeletal muscle in mice. In this study, we tested the effect of different loading conditions on voluntary cage wheel performance and muscle adaptation. Male C57Bl/6 mice were exposed to a cage wheel with no-resistance (NR), low-resistance (LR), or high-resistance (HR) loads for 7 wk. Power output was elevated (3-fold) under increased loading (LR and HR) conditions compared with unloaded (NR) exercise training. Only unloaded (NR) exercise induced an increase in heart mass, whereas only loaded (LR and HR) exercise training induced an increase in skeletal (soleus) muscle mass. Moreover, unloaded and loaded exercise training had a differential impact on the cross-sectional area of muscle fibers, depending on the type of myosin heavy chain expressed by each fiber. The biochemical adaptation of the heart was characterized by a decrease in genes associated with pathological (but not physiological) cardiac hypertrophy and a decrease in calcineurin expression in all exercise groups. In addition, transcriptional activity of myocyte enhancer factor-2 (MEF-2) was significantly decreased in the hearts of the LR group as determined by a MEF-2-dependent transgene driving the expression of β-galactosidase. Phosphorylation of glycogen synthase kinase-3β, protein kinase B (Akt), and p70 S6 kinase was increased only in the hearts of the NR group, consistent with the significant increase in cardiac mass. In conclusion, unloaded and loaded cage wheel exercise have a differential impact on cage wheel performance and muscle (cardiac and skeletal) adaptation.
Hospitality in the First Testament and the ‘Teleological Fallacy’
Authors: Hobbs T. R.
Published: February 2005

This paper recognizes the importance of hospitality in traditional Mediterranean societies as a part of the social fabric of ancient Israel/Judah. The practice as reflected in the First Testament is open to misunderstanding in some modern scholarly literature because some interpretations have been burdened with modern, romantic Western notions of the practice—the ‘teleological fallacy, a tendency to use ancient documents as a springboard for a modern polemic. This paper examines the use of such a notion of hospitality in some recent First Testament studies. It then seeks to establish a fuller model of hospitality, using not only studies of the modern practice, but also historical and ethnographic data from the traditional Mediterranean world. The model is then applied to two important examples of hospitality in the First Testament, 2 Kgs 3.8-34 and 1 Samuel 25.
Reading Lamentations
Authors: Pyper Hugh S.
Published: February 2005

The book of Lamentations is full of imagery of the abandoned and abandoning mother. In this article, following on the work of Tod Linafelt, this is linked to Freud’s analysis of melancholia. The surviving voice in Lamentations turns the anguish of survival into an attack on the mother, reinforced by wider biblical tropes that juxtapose women, food and death. Ultimately, hope is projected on to the continued violence of the father, which is justified at the expense of the mother. The effect of the text on the reader cannot in a simple sense be laid at the writer’s door, however, as an intertextual comparison with Alistair Grey’s novella Five Letters from an Eastern Empire reveals. Later readings have served to enshrine this strategy of survival. The article concludes by arguing that the role of such texts in the Canon may best be understood through their capacity to scandalize the reader into recognition of his or her own complicity in the psychology of destruction.
Genealogical Notes on the ‘House of David’ and the ‘House of Zadok’
Authors: Barrick W. Boyd
Published: February 2005

Genealogical data about the kings of Judah serve as organizational devices in the historiographical literature of the Hebrew Bible. The most conspicuous is there presentation of the ‘House of David’ as a continuous father-to-son succession from David b. Jesse to Jehoiachin b. Jehoiakim for 18 generations (excluding Jehoiakim and Zedekiah who came to the throne irregularly due to foreign intervention, and Athaliah). D.V. Etz has shown this number of consecutive father-to-son successions to be ‘exceptional, if not unique’ (‘The Genealogical Relationships of Jehoram and Ahaziah, and of Ahaz and Hezekiah, Kings of Judah’, JSOT 71 [1996], pp. 39-53 [41]). Deepening the suspicion that something is amiss with this representation are the individual discrepancies in the data available for some of the kings, several of which Etzexamines. This article re-examines the data for these and other reigns to establish a more historically accurate genealogical sequence of kings (the ‘House of David’), and then employs that sequence as a benchmark for advancing a defensible genealogical sequence of high priests (the ‘House of Zadok’) for which the relevant data are much sparser and much more resistant to analysis.
God and Abraham in the Binding of Isaac
Authors: Moltz Howard
Published: February 2005

This article offers a heterodox interpretation of the Binding of Isaac. It makes no claim to decisiveness but rather, in the tradition of the Rabbis, searches within the story to say, ‘This is what the story can mean’. God had commanded that Abraham sacrifice his son, and Abraham had obeyed without hesitation. This article contends that Abraham’s previous history suggests a lack of courage: that as he had surrendered Sarah, first to the Pharaoh of Egypt and then to King Abimelech because he feared he would be killed, so he surrendered Isaac because he feared divine retribution. And God, for his part, imposed his cruel test because he came to doubt Abraham. Ironically, however, the test that demanded the slaughter of the beloved son proved inconclusive, since it was a test of obedience and not of devotion; as such, it failed to address the question of whether Abraham remained in the covenant because of who God is or because of what God had promised. The story ends in a kind of mutual estrangement insofar as God never again speaks to Abraham or Abraham to God; each speaks only about the other and then almost impersonally.
Tendenz and Textual Criticism in 1 Samuel 2–10
Authors: Harvey John E.
Published: February 2005

A dominant feature of the stories in 1 Samuel 2–10 is the striking correspondence that they share with various Tetrateuchal accounts. Correspondences exist between the houses of Eli (1 Sam. 2) and Aaron (Lev. 10; Num. 25); the ark narrative (1 Sam. 4–6) and the plagues narrative (Exod. 5–12); as well as the rejection of divine kingship (1Sam. 8) and the rebellion concerning manna (Num. 11). Commentators have failed to note that many of the textual problems of the MT in 1 Samuel 2–10 surface precisely where these Deuteronomistic and Tetrateuchal accounts are parallel. Rather than being scribal errors, many textual problems in 1 Samuel 2–10 are thus the product of Dtr’s citation of, or allusion to, corresponding Tetrateuchal accounts.
Prophetic Criticism—‘What are they Doing?’: The Case of Isaiah—A Methodological Assessment
Authors: Gitay Yehoshua
Published: February 2005

This article maintains that the essence of Prophetic Criticism is methodology. Recently, a new paradigm shift took place in prophetic research, specifically in the study of the book of Isaiah. This article assesses the methodological ground of the new shift and points out that the new paradigm has failed to replace the earlier one (Form Criticism) because it did not succeed in defining its methodological foundation. Instead, another paradigm of research is presented in this article. This new paradigm is Rhetoric, that is, the text as a communicative and argumentative address. The rhetorical reading is an act which studies—through the text itself—the design of a given unit as a response to a given situation.
Isaiah: A Book without an Ending?
Authors: Clements Ronald E.
Published: February 2005

The ending of the Isaiah scroll in Isa. 66.24 has consistently appeared out of keeping with the broader theme and character of the scroll. This feature reflects the wider problem that evidence of literary structures within the scroll correspond only partly with critical attempts to identify the literary units from which it has been constructed. This article examines the significance of recent attempts to identify the apocalyptic unit comprising chs. 5-35 and the relationship of this to chs. 40-55 to which it has been joined.
An Integrated Reading of Psalms 1 and 2
Authors: Cole Robert
Published: February 2005

An analysis of how Psalms 1 and 2 are integrated reveals that both have as their central theme the identical royal and Joshua-like figure who is given absolute victory in battle. The principal focus of Psalm 1 when read in concert with Psalm 2 is not Torah nor wisdom, but rather this individual of kingly and military trappings. These ascriptions of Psalm 1 are made explicit in Psalm 2, where he is portrayed in close relationship with Yahweh as his anointed king and son. His opponents are the scoffing wicked of Psalm 1, identified more specifically as the conspiring earthly kings and nations in Psalm 2. This cabal revolts against Yahweh and his anointed, an action which elicits the question ‘Why?’ from the speaker in 2.1 because of the promise in 1.5, 6. Yahweh and his anointed respond appropriately to the earthly scoffing with laughter and derision from heaven. Psalm 2 then concludes with a reaffirmation of the same judgment promised at the conclusion of Psalm 1.
Is Joab a Reader-Response Critic?
Authors: Bodner Keith
Published: February 2005

Throughout the David story, Joab is a complex and intriguing character. He frequently disregards or undermines the king’s authority, yet it is possible to argue that his actions are crucial for David’s hold on power to continue. A noticeable pattern of ‘interpretative license’ emerges when Joab’s conduct is analyzed through the numerous vicissitudes in the course of the narrative. Such interpretative license is acutely seen in 2 Samuel 11, where Joab receives David’s letter outlining the manner in which Uriah is to be killed, yet proceeds to implement his own version of the king’s plan. This act of ‘reader-response criticism’, as it is rather playfully appropriated in this study, is consistent with a number of Joab’s other (mis)deeds in the narrative. While his interpretative license arguably benefits his employer, in the end it would appear as though this kind of hermeneutical creativity has lethal consequences for Joab once Solomon enters the scene.
That’s No Literature, That’s My Bible: On James Kugel’s Objections to the Idea of Biblical Poetry
Authors: Raphael Rebecca
Published: February 2005

In The Idea of Biblical Poetry, James Kugel dismantles attempts to find a meter in biblical parallelism. In the process, he implicitly locates the distinction between sacred and secular texts in the formal aspects of the language. This paper challenges Kugel’s main assumptions. First, the premise that poetry must be metrical is controversial, not given, in the history of literary criticism. Second, the formal properties of language do not prove anything about the significance attributed to the forms. I argue that the categories of ‘literature’ and ‘scripture’ cannot be reduced to the presence or absence of formal qualities. The distinction between sacred and secular texts requires consideration of the relation a community of readers takes toward a text. Future discussions of biblical poetry should incorporate relational issues, not just formal ones.
Yehoshua Gitay: ‘What is He Doing?’
Authors: Conrad Edgar W.
Published: February 2005

This article provides a response to an article by Yehoshua Gitay, ‘Prophetic Criticism—“What are they Doing?”: The Case of Isaiah—A Methodological Assessment’ ( JSOT 96), in which he assesses the articles in the volume, New Visions of Isaiah. These articles were originally delivered as papers to the Formation of the Book of Isaiah Seminar of the Society of Biblical Literature. Gitay characterizes the entire work of the Seminar as having a redaction-critical focus. I argue that to characterize my article as representing a redaction-critical approach is to misunderstand what others and I were doing as participants in the Isaiah seminar. My article was in fact a critique of redaction criticism and its author-centred approach to textual meaning.
The Conceptual Dynamics of Good and Evil in the Joseph Story: An Exegetical and Hermeneutical Inquiry
Authors: Jacobs Mignon R.
Published: February 2005

This article examines the dynamics of good and evil as represented in the Joseph story (Gen. 37-50). It examines the story’s plot, the larger conceptual framework of the narrative’s Pentateuchal setting, as well as the semantic indicators and associated attitudes/behaviors qualified as good ([ILLEGIBLE]) and/or evil ([ILLEGIBLE]). The main objectives of this article are: (1) to identify the main issues within the story’s concept of the dynamics of good and evil; (2) to promote a more thorough consideration of the place of Joseph and God in those dynamics; and (3) to generate hermeneutical inquiries about the dynamics of good and evil using the insights gained from this examination—inquiries that are more relevant to contemporary discussion (e.g. understanding human atrocities, forgiveness, and reconciliation).
Narrative Obscurity of Samson’s [ILLEGIBLE] in Judges 14.14 and 18
Authors: Schipper Jeremy
Published: February 2005

Scholars have often found Judg. 14.18 to be an unsatisfactory solution to Samson’s riddle in 14.14. This situation has prompted a number of alternative scholarly proposals, which attempt to settle the riddle’s unresolved aspects and restore a solution. Yet the complex relationship between the riddle and the narrative that surrounds it has received little attention. The information provided by the surrounding narrative obscures the riddle’s meaning and resists any attempt to locate an unambiguous solution. While it should help to clarify the riddle’s solution, the narrative actually creates an obscuring atmosphere that calls the reader to respond to the riddle by following a variety of interpretive trajectories running throughout the Samson story.
The Composition of the Elijah-Elisha Stories and the Deuteronomistic History
Authors: Otto Susanne
Published: February 2005

This article argues that the development of the text within 1 Kgs 16.29- 2 Kgs 10.36 can be described in four major stages. First, the Deuteronomistic History—which was composed shortly after 562 BCE—contained only three of the Elijah-Elisha stories: the narratives about Naboth’s vineyard, Ahaziah’s death and the story of Jehu’s coup. By means of the epoch from Ahab to Jehu the Deuteronomists demonstrated the reliability of the word of God throughout history. Further, they embodied the theme ‘Baal worship—cultic reform’ in the history of the Northern Kingdom. Second, shortly after the narratives about the Omride wars were added and a new theme introduced: the attitude of the king towards the word of the prophets determines the fate of Israel. Third, in early post-exilic times, 1 Kings 17-18 was added to demonstrate the possibility of a new life in community with God after the time of judgment. Fourth, in the fifth century, 1 Kgs 19.1-18 and the remaining Elisha stories were inserted to give prophecy a legitimate foundation in the history of Israel.
Violent Grace: Tragedy and Transformation in the Oresteia and the Deuteronomistic History
Authors: Hawk L. Daniel
Published: February 2005

The Oresteia of Aeschylus and the establishment of the Israelite monarchy (1 Sam. 8-2 Kgs 8) display a striking concurrence in structure and characterization. Each employs a tripartite scheme and deft use of metaphor to relate a transformation from an old kin-based social order to a new civic society. The first segment (Agamemnon and Saul) brings together the motifs of kingship, vendetta, and sacrifice to portray the disintegration of the old order. The second (Orestes and David) effects a transition through the stories of complex characters associated with youth and the wilderness. Finally, agents of wisdom (Athena and Solomon) establish mediating institutions on the sacred hill of the city, signifying the inauguration of a new social and cosmic order.
Satire in Isaiah’s Tyre Oracle
Authors: Lessing Reed
Published: February 2005

Most scholars believe that Isaiah’s Tyre Oracle is a prophetic lament. This article argues that Isa. 23.1-14 is best understood as a predictive satirical city-lament. In order to make this case, both prophetic satire and the genre of a city-lament are defined. A translation of Isa. 23.1-14 is followed by an investigation of the text’s context, verbal markers and perceptible contradictions. Observations on Ezekiel’s oracle against Tyre (27.1-11, 26-36) lead to the conclusion that the genre of a city-lament requires treating the downfall as a past event, whereas in terms of history it is still in the future.
‘Then Israel Bowed Himself…’ (Genesis 47.31)
Authors: de Hoop Raymond
Published: February 2005

In Gen. 47.31b we find the phrase [ILLEGIBLE], which is generally interpreted as ‘then Israel bowed himself at the head of the bed’. Yet this interpretation does not make much sense in the context and commentators are puzzled about its meaning. This article surveys the possible meaning of the phrase with the help of the LXX and Peshitta, traditions which interpret the final word [ILLEGIBLE] as ‘staff’. The rendering of the Versions suggests a possible meaning of ‘staff, tribe’ for the Hebrew term, leading to the more common interpretation of [ILLEGIBLE] [ILLEGIBLE] as ‘head of the tribe’. The suggested interpretation implies that the dying patriarch bowed down for the new pater familias, Joseph. Finally some considerations are given regarding the historical context in which Joseph appears as the new pater familias, the successor of his father, the patriarch Israel.
Ignatian spirituality as transformational social science
Authors: Coghlan David
Published: February 2005

The value of spirituality in organizational life and in social research is becoming increasingly recognized by members of organisations and by social science researchers. In this article, the motifs of Ignatian spirituality, the heritage of Ignatius of Loyola (1491–1556) – a transformational spirituality in the Roman Catholic tradition in which action is a central motif – are introduced and explored in terms of some of the main tenets of action research. This article shows how Ignatian spirituality contributes a faith-based transformational methodology to the field of action research.
A Theory of Mind investigation into the appreciation of visual jokes in schizophrenia
Authors: Marjoram Dominic , Tansley Howard , Miller Patrick , MacIntyre Donald , Owens David G Cunningham , Johnstone Eve C , Lawrie Stephen
Published: February 2005

Background

There is evidence that groups of people with schizophrenia have deficits in Theory of Mind (ToM) capabilities. Previous studies have found these to be linked to psychotic symptoms (or psychotic symptom severity) particularly the presence of delusions and hallucinations.

Methods

A visual joke ToM paradigm was employed where subjects were asked to describe two types of cartoon images, those of a purely Physical nature and those requiring inferences of mental states for interpretation, and to grade them for humour and difficulty. Twenty individuals with a DSM-lV diagnosis of schizophrenia and 20 healthy matched controls were studied. Severity of current psychopathology was measured using the Krawiecka standardized scale of psychotic symptoms. IQ was estimated using the Ammons and Ammons quick test.

Results

Individuals with schizophrenia performed significantly worse than controls in both conditions, this difference being most marked in the ToM condition. No relationship was found for poor ToM performance and psychotic positive symptomatology, specifically delusions and hallucinations.

Conclusion

There was evidence for a compromised ToM capability in the schizophrenia group on this visual joke task. In this instance this could not be linked to particular symptomatology.
Plant viral intergenic DNA sequence repeats with transcription enhancing activity
Authors: Velten Jeff , Morey Kevin J , Cazzonelli Christopher I
Published: February 2005

Background

The geminivirus and nanovirus families of DNA plant viruses have proved to be a fertile source of viral genomic sequences, clearly demonstrated by the large number of sequence entries within public DNA sequence databases. Due to considerable conservation in genome organization, these viruses contain easily identifiable intergenic regions that have been found to contain multiple DNA sequence elements important to viral replication and gene regulation. As a first step in a broad screen of geminivirus and nanovirus intergenic sequences for DNA segments important in controlling viral gene expression, we have 'mined' a large set of viral intergenic regions for transcriptional enhancers. Viral sequences that are found to act as enhancers of transcription in plants are likely to contribute to viral gene activity during infection.

Results

DNA sequences from the intergenic regions of 29 geminiviruses or nanoviruses were scanned for repeated sequence elements to be tested for transcription enhancing activity. 105 elements were identified and placed immediately upstream from a minimal plant-functional promoter fused to an intron-containing luciferase reporter gene. Transient luciferase activity was measured within Agrobacteria-infused Nicotiana tobacum leaf tissue. Of the 105 elements tested, 14 were found to reproducibly elevate reporter gene activity (>25% increase over that from the minimal promoter-reporter construct, p < 0.05), while 91 elements failed to increase luciferase activity. A previously described "conserved late element" (CLE) was identified within tested repeats from 5 different viral species was found to have intrinsic enhancer activity in the absence of viral gene products. The remaining 9 active elements have not been previously demonstrated to act as functional promoter components.

Conclusion

Biological significance for the active DNA elements identified is supported by repeated isolation of a previously defined viral element (CLE), and the finding that two of three viral enhancer elements examined were markedly enriched within both geminivirus sequences and within Arabidopsis promoter regions. These data provide a useful starting point for virologists interested in undertaking more detailed analysis of geminiviral promoter function.
Controlling Neuropathic Pain by Adeno-Associated Virus Driven Production of the Anti-Inflammatory Cytokine, Interleukin-10
Authors: Milligan Erin D , Sloane Evan M , Langer Stephen J , Cruz Pedro E , Chacur Marucia , Spataro Leah , Wieseler-Frank Julie , Hammack Sayamwong E , Maier Steven F , Flotte Terence R , Forsayeth John R , Leinwand Leslie A , Chavez Raymond , Watkins Linda R
Published: February 2005

Despite many decades of drug development, effective therapies for neuropathic pain remain elusive. The recent recognition of spinal cord glia and glial pro-inflammatory cytokines as important contributors to neuropathic pain suggests an alternative therapeutic strategy; that is, targeting glial activation or its downstream consequences. While several glial-selective drugs have been successful in controlling neuropathic pain in animal models, none are optimal for human use. Thus the aim of the present studies was to explore a novel approach for controlling neuropathic pain. Here, an adeno-associated viral (serotype II; AAV2) vector was created that encodes the anti-inflammatory cytokine, interleukin-10 (IL-10). This anti-inflammatory cytokine is known to suppress the production of pro-inflammatory cytokines. Upon intrathecal administration, this novel AAV2-IL-10 vector was successful in transiently preventing and reversing neuropathic pain. Intrathecal administration of an AAV2 vector encoding beta-galactosidase revealed that AAV2 preferentially infects meningeal cells surrounding the CSF space. Taken together, these data provide initial support that intrathecal gene therapy to drive the production of IL-10 may prove to be an efficacious treatment for neuropathic pain.
ANKHvariants associated with ankylosing spondylitis: gender differences
Authors: Tsui Hing Wo , Inman Robert D , Paterson Andrew D , Reveille John D , Tsui Florence WL
Published: February 2005

The ank (progressive ankylosis) mutant mouse, which has a nonsense mutation in exon 12 of the inorganic pyrophosphate regulator gene (ank), exhibits aberrant joint ankylosis similar to human ankylosing spondylitis (AS). We previously performed family-based association analyses of 124 Caucasian AS families and showed that novel genetic markers in the 5' flanking region of ANKH (the human homolog of the murine ank gene) are modestly associated with AS. The objective of the present study was to conduct a more extensive evaluation of ANKH variants that are significantly associated with AS and to determine whether the association is gender specific. We genotyped 201 multiplex AS families with nine ANKH intragenetic and two flanking microsatellite markers, and performed family-based association analyses. We showed that ANKH variants located in two different regions of the ANKH gene were associated with AS. Results of haplotype analyses indicated that, after Bonferroni correction, the haplotype combination of rs26307 [C] and rs27356 [C] is significantly associated with AS in men (recessive/dominant model; P = 0.004), and the haplotype combination of rs28006 [C] and rs25957 [C] is significantly associated with AS in women (recessive/dominant model; P = 0.004). A test of interaction identified rs26307 (i.e. the region that was associated in men with AS) as showing a difference in the strength of the association by gender. The region associated with AS in women only showed significance in the test of interaction among the subset of families with affected individuals of both genders. These findings support the concept that ANKH plays a role in genetic susceptibility to AS and reveals a gender–genotype specificity in this interaction.
Intrathecal Mafosfamide: A Preclinical Pharmacology and Phase I Trial
Authors: Blaney Susan M. , Balis Frank M. , Berg Stacey , Arndt Carola A.S. , Heideman Richard , Geyer J. Russell , Packer Roger , Adamson Peter C. , Jaeckle Kurt , Klenke Renee , Aikin Alberta , Murphy Robert , McCully Cynthia , Poplack David G.
Published: February 2005

Purpose

Preclinical studies of mafosfamide, a preactivated cyclophosphamide analog, were performed to define a tolerable and potentially active target concentration for intrathecal (IT) administration. A phase I and pharmacokinetic study of IT mafosfamide was performed to determine a dose for subsequent phase II trials.

Patients and Methods

In vitro cytotoxicity studies were performed in MCF-7, Molt-4, and rhabdomyosarcoma cell lines. Feasibility and pharmacokinetic studies were performed in nonhuman primates. These preclinical studies were followed by a phase I trial in patients with neoplastic meningitis. There were five dose levels ranging from 1 mg to 6.5 mg. Serial CSF samples were obtained for pharmacokinetic studies in a subset of patients with Ommaya reservoirs.

Results

The cytotoxic target exposure for mafosfamide was 10 μmol/L. Preclinical studies demonstrated that this concentration could be easily achieved in ventricular CSF after intraventricular dosing. In the phase I clinical trial, headache was the dose-limiting toxicity. Headache was ameliorated at 5 mg by prolonging the infusion rate to 20 minutes, but dose-limiting headache occurred at 6.5 mg dose with prolonged infusion. Ventricular CSF mafosfamide concentrations at 5 mg exceeded target cytotoxic concentrations after an intraventricular dose, but lumbar CSF concentrations 2 hours after the dose were less than 10 μmol/L. Therefore, a strategy to alternate dosing between the intralumbar and intraventricular routes was tested. Seven of 30 registrants who were assessable for response had a partial response, and six had stable disease.

Conclusion

The recommended phase II dose for IT mafosfamide, administered without concomitant analgesia, is 5 mg over 20 minutes.
Health Care Provider-Directed Intervention to Increase Colorectal Cancer Screening Among Veterans: Results of a Randomized Controlled Trial
Authors: Ferreira M. Rosario , Dolan Nancy C. , Fitzgibbon Marian L. , Davis Terry C. , Gorby Nicolle , Ladewski Lisa , Liu Dachao , Rademaker Alfred W. , Medio Franklin , Schmitt Brian P. , Bennett Charles L.
Published: February 2005

Purpose

Colorectal cancer screening is the most underused cancer screening tool in the United States. The purpose of this study was to test whether a health care provider–directed intervention increased colorectal cancer screening rates.

Patients and Methods

The study was a randomized controlled trial conducted at two clinic firms at a Veterans Affairs Medical Center. The records of 5,711 patients were reviewed; 1,978 patients were eligible. Eligible patients were men aged 50 years and older who had no personal or family history of colorectal cancer or polyps, had not received colorectal cancer screening, and had at least one visit to the clinic during the study period. Health care providers in the intervention firm attended a workshop on colorectal cancer screening. Every 4 to 6 months, they attended quality improvement workshops where they received group screening rates, individualized confidential feedback, and training on improving communication with patients with limited literacy skills. Medical records were reviewed for colorectal cancer screening recommendations and completion. Literacy level was assessed in a subset of patients.

Results

Colorectal cancer screening was recommended for 76.0% of patients in the intervention firm and for 69.4% of controls (P = .02). Screening tests were completed by 41.3% of patients in the intervention group versus 32.4% of controls (P = .003). Among patients with health literacy skills less than ninth grade, screening was completed by 55.7% of patients in the intervention group versus 30% of controls (P < .01).

Conclusion

A provider-directed intervention with feedback on individual and firm-specific screening rates significantly increased both recommendations and colorectal cancer screening completion rates among veterans.
Impact of αENaC Polymorphisms on the Risk of Ischemic Cerebrovascular Events: A Multicenter Case–Control Study
Authors: Hsieh Kety , Lalouschek Wolfgang , Schillinger Martin , Endler Georg , Reisinger Manuela , Janisiw Michael , Lang Wilfried , Cheng Suzanne , Wagner Oswald , Mannhalter Christine
Published: February 2005

Background: Amiloride-sensitive epithelial sodium channels (ENaCs) are important candidates in the development of hypertension, which is a major risk factor for stroke. Two single-nucleotide polymorphisms (SNPs) in the gene that encodes the ENac α-subunit (αENaC) have been identified. We evaluated those SNPs for a possible association with ischemic cerebrovascular events (ICEs).

Methods and Results: We genotyped 1399 patients with ICEs [median age, 70 years; interquartile range, 58–78 years; 745 (53%) men] and 1076 control individuals without vascular disease [47 (39–58) years; 557 (52%) men] for the SNPs Trp493Arg and Ala663Thr. The SNP frequencies at nucleotide 3977 (Trp493Arg) in the αENaC gene were significantly different in patients and controls. Carriers of 493Arg had a 1.78-fold increased risk (95% confidence interval, 1.02–3.12) for ICEs compared with Trp/Trp carriers. Interaction analysis revealed that the relative risk was even higher in women in the lowest age tertile [adjusted odds ratio, 3.26 (1.10–9.72)].

Conclusions: Carriers of the 493Arg allele are at increased risk for ICEs compared with Trp/Trp carriers. The effect is independent of traditional vascular risk factors and is particularly evident in younger women. The Trp493Arg variant in αENaC may represent an important candidate genetic susceptibility factor in the development of ICEs.
The blood supply of the bovine hypophysis
Authors: Cummings J. F. , Habel R. E.
Published: February 2005

The rete mirabile cerebri and the hypophysial vascularization were studied by various injection and staining techniques. The rostral hypophysial arteries arose bilaterally from the arterial circle of the cerebrum, while the caudal hypophysial arteries arose from the rete miabile on the dosal and caudal surfaces of the gland. The ramifications of the rostral hypophysial arteries supplied the vascular structures in the hypophysial stalk, which were classified on the basis of their structure into three groups; arborization forms, spike forms, and capillary loops. These structures drained into large portal vessels leading to the pars distalis. The pars distalis received a second smaller group of portal vessels from the capillary bed of the lower infundibular stem. The small group of portal vessels was limited in its extent by a well‐developed hypophysial cleft. No direct arterial supply to the pars distalis could be demonstrated. The findings of this study support the view that the blood in the hypophysial portal system flows distally from the hypophysial stalk to the pars distalis.
A comparative‐anatomical study of the craniocervical venous systems in mammals, with special reference to the dog: Relationship of anatomy to measurements of cerebral blood flow
Authors: Hegedus Stephen A. , Shackelford Richard T.
Published: February 2005

Pathways of the venous drainage from brain have been studied in various mammals to locate sites for cerebral venous blood sampling with least potential admixture of blood of extracerebral origin.

Man, rhesus monkey, pig and cat have internal jugular veins leaving the intracranial cavity through the jugular foramina (foramen lacerum). The bulb of the internal jugular vein may be used for withdrawal of cerebral venous blood in this group of species possessing the embryonal type of cerebral venous system.

Dog, horse, rabbit, sheep and ox have (superior) dorsal cerebral veins leaving the intracranial cavity through the temporal foramina as the major cerebral venous outflow. The internal jugular vein in this group arises from the pharyngeal, thyroid and esophageal veins and has infrequent and very small or no drainage of cerebral blood from cerebral venous sinuses. On a dog and even more on other mammals of this group in horizontal and supine position, cerebral venous blood rarely can be obtained without significant contamination with extracerebral blood if the sampling takes place centrally from the temporal foramen.

On a prone positioned dog the posterior third of the (superior) dorsal longitudinal sinus is the site to obtain cerebral venous blood specimens with minimal admixture of extracerebral blood.
The ultrastructure of unilaminar follicles of the hamster ovary
Authors: Odor D. Louise
Published: February 2005

Unilaminar follicles consisting of primary oocytes surrounded by a single granulosal layer, composed either of flattened, cuboidal or columnar cells, have been studied with the electron microscope in normal prepubertal hamsters. The most striking feature of the oocyte cytoplasm is the occurrence of the mitochondria in small groups with a dense intermitochondrial substance lying between the individual mitochondria. This substance is composed mainly of very small vesicles with a dense profile and a light center. Some of the mitochondria do not appear to have a limiting membrane, their matrices being seemingly continuous with, and similar in structure to, the intermitochondrial substance. In the younger oocytes the Golgi complex is diffuse and has numerous small vesicles. The nucleoli of the young oocytes are large and complex. They consist of a lighter area, predominantly of small particulate elements, and of darker regions, mainly with fine fibrillar components. The initial steps in the formation of the zona pellucida take place in follicles with a single layer of cuboidal granulosa cells. By the time the oocyte is surrounded by a single layer of columnar granulosa cells a continuous zona pellucida within which lies oocyte microvilli and granulosa cell processes is present.
Studies on the thymus of the mammal. XIV. Histology and histochemistry of embryonic and early postnatal thymuses of C57Bl/6 and AKR strain mice
Authors: Smith Christianna
Published: February 2005

Thymuses of mice of the C57B1/6 and AKR strains from ten‐day‐old embryos through one day after birth were studied histologically and histochemically. New evidence is presented of the penetration of the endodermal epithelium of the third pharyngeal pouch of ten‐day‐old embryos by basophilic lymphoblasts.

Both alkaline and acid phosphatases showed different distributions in the thymuses of the two strains at 12 and 13 days. By 15 and 16 days, alkaline phosphatase activity in thymuses of the C57B1/6 strain was peripheral; in thymuses of AKR mice, it was present throughout the lobes. In the C57B1/6 lobes, little acid phosphatase activity was observed; however, in the AKR thymuses, activity was strong and was located especially in the cortex. The characteristic patterns of enzymatic activities of the postnatal thymuses were well established at 17–18 days. Prenatally the medullae of the thymuses of both strains contained esterase‐rich inclusion cells and epithelial reticular cells which occurred singly or as nests of cells. The inclusion cells also possessed alkaline phosphatase activity. It is suggested that these cells may contain the precursors of the humoral factor(s) of the thymus. The thymuses were also studied after treatment with the periodic acid‐Schiff technique for glycogen and the procedure for showing sites of adenosine triphosphatase activity.
Patterns of origin and distribution of the major bronchial arteries in man
Authors: Liebow Averill A.
Published: February 2005

In 50 lungs prepared as casts, the most common pattern of arrangement of the bronchial arteries, occurring in 30% of all lungs, was that of two posterior bronchial trunks to each side; next in frequency was the pattern of two trunks to the left and one to the right lung. In more than three‐fourths of all cases there were not more than two bronchial arteries on each side. In two‐thirds of the specimens various bronchial arteries arose both directly from the aorta and indirectly from an intercosto‐bronchial trunk. At least one intercosto‐bronchial trunk was present in 37 of the 50 specimens. All such trunks, even those supplying the left lung, took origin from the right side of the aorta, almost always from the first or second posterior segmental aortic branches, i.e., at the level of the fifth or sixth thoracic vertebra. Almost all intercosto‐bronchial trunks yielded a right bronchial artery. Approximately 84% of the left bronchial arteries sprang directly from the aorta. In 22% a single trunk was the source of all bronchial arteries to both lungs, and in 14% this trunk arose directly from the aorta. In 84% also there was at least one bronchial artery that supplied bronchi of both lungs.

Arteries arising high on the anterior or right lateral surface of the aorta were found in more than one‐half of the casts, more than three times as frequently as in previously reported dissections.
The distribution within the brain of ferritin injected into cerebrospinal fluid compartments. II. Parenchymal distribution
Authors: Brightman Milton W.
Published: February 2005

The electron lucent channels, about 200 Å‐wide, between the plasma‐lemmas of adjacent cell processes within the brain are true pericellular spaces along which ferritin molecules can move. The micelles, visualized electronmicroscopically, move through the spaces until they encounter an interglial fusion or its myelin counterpart. The interspace between glial processes is abruptly sealed by these inter‐membranous fusions or occasionally distended by a dense filler capable of trapping ferritin. The cerebral interspace is thus highly variable in width and content.

Molecules initially enter the interspace by passing across the basement membrane of the glial border fronting the subarachnoid space whence they are pinocytosed by the underlying glial processes and, at the subarachnoid border of the anterior medullary velum, by also passing directly between adjacent ependymal extensions. Once having entered the parenchymal interspace, micelles can be pinocytosed by neuronal somata and processes and, to a greater degree, by glial fibers. Pinocytosis by the thicker rather than the attenuated portions of glial fibers suggests that the plasmalemmas on the opposite sides of a process must be separated by a critical distance before pinocytotic indentations can be formed. The thinner portions thus offer greater barriers to the movement of micelles than do thicker regions.
A histochemical study of testosterone‐induced changes in the submandibular and sublingual gland of mice
Authors: Kronman Joseph H. , Spinale Joseph J.
Published: February 2005

Prior studies have established a definite interrelationship between the salivary glands and the endocrine system. This study was designed to histochemically characterize testosterone‐induced changes in the submandibular and the sublingual glands of male and female Ajax strain mice. In addition to morphologic stains, histochemical procedures included the demonstration of tryptophan, tyrosine, and sulfhydryl groups. Alcian blue, PAS, and toluidine blue staining was also employed. The Gomori and azo dye coupling procedures were both utilized for the demonstration of alkaline phosphatase.
Immunohistological and histochemical localization of relaxin in the metrial gland of the pregnant rat
Authors: Dallenbach‐Hellweg G. , Battista J. V. , Dallenbach F. D.
Published: February 2005

The presence of relaxin in uteri, placentae, and ovaries of pregnant rats was studied immunohistologically with fluorescein labeled anti‐relaxin serum and confirmed by histological and histochemical techniques.

In sections of uteri from day 12 of pregnancy stained with these antisera, the cytoplasm of the granular cells of the mesometrial decidua gave off a yellow‐green fluorescence indicating antirelaxin binding. On day 15, 17 and 19, the granular cells of the metrial gland and occasional lakes in near‐by vascular lumina fluoresced. No other specific fluorescence was evident in the uteri or placentae. The fluorescent regions of these cells corresponded exactly with the cytoplasmic aggregates of granules in the metrial gland and mesometrial decidua. Histochemical studies of these granules which bound with antirelaxin, revealed a chemical composition congruent with that known for relaxin, and with that of the relaxin‐containing granules of human decidual and placental cells. The dissolution of connective tissue fibers, believed to be a main function of relaxin, was observed in the last days of pregnancy within the metrial gland, especially where it borders the mesometrial decidua. These results correlate well with Schaub's discovery of a collagen‐degrading substance in the metrial gland. Other actions of relaxin may be explained as secondary to the primary effect of dissolution of collagen. The relaxin‐containing cells in the human and in the rat differ only in their localization in the tissue which depends on their phylogenetic adaptation to different placentational needs. The metrial gland cells of the pregnant rat correspond in their function to the basal trophoblastic cells of the human term placenta. The non‐menstruating rat has no counterpart for the endometrial granulocytes, but the granular cells in the mesometrial decidua adjacent to the site of implantation correspond to the endometrial granular cells surrounding the implantation site in the human; it is suggested their collagen dissolving action facilitates implantation.
The fine structure of nerve endings in the nucleus of the trapezoid body and the ventral cochlear nucleus
Authors: Lenn Nicholas J. , Reese T. S.
Published: February 2005

Large, calyciform axonal endings, as well as typical terminal boutons, have been previously described in the ventral cochlear nucleus and the nucleus of the trapezoid body by light microscopists. In the present study, these endings were examined with the electron microscope in chinchillas, rats, and a cat after perfusion fixation with osmium tetroxide. The calyces were found to consist of elongated processes arising from myelinated axons and making multiple synaptic contacts with perikarya and dendrites. This finding suggests that an important property of calyces is the large amount of synaptic activity that they can bring to bear on a single post‐synaptic structure. Adjacent to the calyciform endings were variable numbers of boutons that made synaptic contacts with the same perikarya and dendrites. The majority of boutons contained smaller synaptic vesicles than those present in the calyces, implying both anatomical and functional differences between these two types of ending. It is suggested that many of these boutons in the ventral cochlear nucleus are endings of centrifugal, inhibitory fibers described by previous workers.