bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutual obligation, shared responsibility agreements & indigenous health strategy
Authors: Anderson Ian PS
Published: September 2006

Since 2004 the Howard Coalition government has implemented a new policy framework and administrative arrangements as part of its program of reform in Indigenous affairs. In this paper I will describe both the parameters of this reform program and review the processes established to support the implementation of national Indigenous health strategy. In particular, I will consider both the shift from a policy framework based on 'self-determination' to one based on 'mutual obligation', and the implementation of Shared Responsibility Agreements (SRAs) that are based on the latter principle. I will use the example of the Mulan SRA to illustrate the difficulties in articulating the 'new arrangements' with current approaches to Indigenous health planning and strategy implementation. I conclude that 'new arrangements' pose a number of problems for Indigenous health planning and strategy that need to be addressed.
Pain-Related Synaptic Plasticity in Spinal Dorsal Horn Neurons: Role of CGRP
Authors: Bird Gary C , Han Jeong S , Fu Yu , Adwanikar Hita , Willis William D , Neugebauer Volker
Published: September 2006

Background

The synaptic and cellular mechanisms of pain-related central sensitization in the spinal cord are not fully understood yet. Calcitonin gene-related peptide (CGRP) has been identified as an important molecule in spinal nociceptive processing and ensuing behavioral responses, but its contribution to synaptic plasticity, cellular mechanisms and site of action in the spinal cord remain to be determined. Here we address the role of CGRP in synaptic plasticity in the spinal dorsal horn in a model of arthritic pain.

Results

Whole-cell current- and voltage-clamp recordings were made from substantia gelatinosa (SG) neurons in spinal cord slices from control rats and arthritic rats (> 6 h postinjection of kaolin/carrageenan into the knee). Monosynaptic excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation of afferents in the dorsal root near the dorsal root entry zone. Neurons in slices from arthritic rats showed increased synaptic transmission and excitability compared to controls. A selective CGRP1 receptor antagonist (CGRP8-37) reversed synaptic plasticity in neurons from arthritic rats but had no significant effect on normal transmission. CGRP facilitated synaptic transmission in the arthritis pain model more strongly than under normal conditions where both facilitatory and inhibitory effects were observed. CGRP also increased neuronal excitability. Miniature EPSC analysis suggested a post- rather than pre-synaptic mechanism of CGRP action.

Conclusion

This study is the first to show synaptic plasticity in the spinal dorsal horn in a model of arthritic pain that involves a postsynaptic action of CGRP on SG neurons.
Human monocyte-derived dendritic cells express TLR9 and react directly to the CpG-A oligonucleotide D19
Authors: Hoene Victoria , Peiser Matthias , Wanner Reinhard
Published: September 2006

Oligodeoxynucleotides (ODNs) containing unmethylated CpG exhibit their immunostimulatory activities by binding to TLR. Here, we show that human monocyte-derived dendritic cells (moDC) contain TLR9 protein, surprisingly, in amounts comparable with plasmacytoid DC (pDC). Immature moDC but not mature moDC nor monocytes captured CpG-ODNs. moDC stimulation with the CpG-A ODN D19 up-regulated CD83, CD86, and HLA-DR. Without CD40 ligand costimulation, full maturation was not achieved. D19-stimulated moDC primed allogeneic CD4+-T cells for proliferation and differentiation into IFN-γ-secreting Th1 cells. Neither IL-12 nor IL-6 or TNF-α was involved. Microarray analysis pointed to a participation of Type I IFNs. In fact, D19-stimulated moDC secreted considerable amounts of IFN-α. This indicates that moDC themselves sense viral and bacterial DNA and do not need help from pDC.
Statins and Cancer Risk: A Literature-Based Meta-Analysis and Meta-Regression Analysis of 35 Randomized Controlled Trials
Authors: Bonovas Stefanos , Filioussi Kalitsa , Tsavaris Nikolaos , Sitaras Nikolaos M.
Published: September 2006

Purpose

A growing body of literature suggests that statins may have chemopreventive potential against cancer. Our aim was to examine the strength of this association through a detailed meta-analysis and meta-regression analysis of randomized controlled trials (RCTs).

Methods

A comprehensive search for trials published up to 2005 was performed, reviews of each study were conducted, and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random- and fixed-effects models. Subgroup, sensitivity, and meta-regression analyses were also conducted.

Results

Thirty-five RCTs of statins for cardiovascular outcomes contributed to the analysis (n = 109,143). The degree of variability between trials was consistent with what would be expected to occur by chance alone. Statin use was not associated with a substantially increased or decreased overall risk of cancer (RR = 0.99; 95% CI, 0.94 to 1.04). Similarly, statin use did not significantly affect respiratory cancer risk (RR = 0.95; 95% CI, 0.83 to 1.09). However, the meta-regression analysis indicated that age of study participants modified the association between statin use and cancer risk (P = .003).

Conclusion

Our findings do not support a protective effect of statins against cancer. However, this conclusion is limited by the relatively short follow-up periods (4.5 years on average) of the studies analyzed. Thus, it is important to continue monitoring the long-term safety profiles of statins. Until then, physicians need to be vigilant in ensuring that statin use remains restricted to the approved indications.
RNA aptamers binding the double-stranded RNA-binding domain
Authors: Hallegger Martina , Taschner Andreas , Jantsch Michael F.
Published: September 2006

Specific RNA recognition of proteins containing the double-strand RNA-binding domain (dsRBD) is essential for several biological pathways such as ADAR-mediated adenosine deamination, localization of RNAs by Staufen, or RNA cleavage by RNAse III. Structural analysis has demonstrated the lack of base-specific interactions of dsRBDs with either a perfect RNA duplex or an RNA hairpin. We therefore asked whether in vitro selections performed in parallel with individual dsRBDs could yield RNAs that are specifically recognized by the dsRBD on which they were selected . To this end, SELEX experiments were performed using either the second dsRBD of the RNA-editing enzyme ADAR1 or the second dsRBD of Xlrbpa, a homolog of TRBP that is involved in RISC formation. Several RNA families with high binding capacities for dsRBDs were isolated from either SELEX experiment, but no discrimination of these RNAs by different dsRBDs could be detected. The selected RNAs are highly structured, and binding regions map to two neighboring stem–loops that presumably form stacked helices and are interrupted by mismatches and bulges. Despite the lack of selective binding of SELEX RNAs to individual dsRBDS, selected RNAs can efficiently interfere with RNA editing in vivo.
The global structures of a wild-type and poorly functional plant luteoviral mRNA pseudoknot are essentially identical
Authors: Cornish Peter V. , Stammler Suzanne N. , Giedroc David P.
Published: September 2006

The helical junction region of a −1 frameshift stimulating hairpin-type mRNA pseudoknot from sugarcane yellow leaf virus (ScYLV) is characterized by a novel C27·(G7–C14) loop 2–stem 1 minor groove base triple, which is stacked on a C8+·(G12–C28) loop 1–stem 2 major groove base triple. Substitution of C27 with adenosine reduces frameshifting efficiency to a level just twofold above the slip-site alone. Here, we show that the global structure of the C27A ScYLV RNA is nearly indistinguishable from the wild-type counterpart, despite the fact that the helical junction region is altered and incorporates the anticipated isostructural A27·(G7–C14) minor groove base triple. This interaction mediates a 2.3-Å displacement of C8+ driven by an A27 N6–C8+ O2 hydrogen bond as part of an A(n−1)·C+·G-Cn base quadruple. The helical junction regions of the C27A ScYLV and the beet western yellows virus (BWYV) pseudoknots are essentially superimposable, the latter of which contains an analogous A25·(G7–C14) minor groove base triple. These results reveal that the global ground-state structure is not strongly correlated with frameshift stimulation and point to a reduced thermodynamic stability and/or enhanced kinetic lability that derives from an altered helical junction architecture in the C27A ScYLV RNA as a significant determinant for setting frameshifting efficiencies in plant luteoviral mRNA pseudoknots.
Price Competition with the Attraction Demand Model: Existence of Unique Equilibrium and Its Stability
Authors: Gallego Guillermo , Huh Woonghee Tim , Kang Wanmo , Phillips Robert
Published: September 2006

We show the existence of Nash equilibria in a Bertrand oligopoly price competition game using a possibly asymmetric attraction demand model with convex costs under mild assumptions. We show that the equilibrium is unique and globally stable. To our knowledge, this is the first paper to show the existence of a unique equilibrium with both nonlinear demand and nonlinear costs. In addition, we guarantee the linear convergence rate of tatônnement. We illustrate the applicability of this approach with several examples arising from operational considerations that are often ignored in the economics literature.
Disentangling the Effects of CEO Turnover and Succession on Organizational Capabilities: A Social Network Perspective
Authors: Cao Qing , Maruping Likoebe M. , Takeuchi Riki
Published: September 2006

Prior reviews of the CEO turnover and succession literature suggest that empirical findings on organizational implications continue to be equivocal. In this paper, we develop a conceptual framework for examining the impact of CEO turnover and succession on organizational capabilities. Using the social network perspective as a theoretical lens, we identify conditions in which CEO turnover is expected to influence organizational exploration and exploitation capabilities. We also identify contingencies under which CEO succession will moderate the impact of CEO turnover on organizational capabilities. Our framework provides a useful lens through which to view the consequences of CEO turnover and succession and sheds some light on the equivocal findings to date.
The Ecological Interdependence of Emergent and Established Organizational Populations: Legitimacy Transfer, Violation by Comparison, and Unstable Identities
Authors: Dobrev Stanislav D. , Ozdemir Salih Zeki , Teo Albert C.
Published: September 2006

We know that organizations of different but related kinds greatly influence each other’s evolution. Although empirical findings abound, the theories behind them are still being developed. We advance a model of ecological interdependence between emergent and established populations. Our model is based on three main ideas. First, we consider related populations to be those that overlap in identity and resource space and that simultaneously exhibit competitive and mutualistic relationships, the latter leading to legitimacy transfer. Second, we build on the idea that legitimated forms codify prescriptive sanctions for deviations from identity blueprints, and predict that when an emergent population overlaps with an established one in identity space, its early proliferation will manifest violations of established social identities and will trigger prescriptive sanctions. Third, we rely on the notion of a focused identity to argue that organization-level changes affect external perceptions of the population’s collective identity, and hamper legitimacy. Analysis of the survival rates of financial cooperatives in Singapore—a population overlapping the identity and resources of commercial banks—confirms our predictions.
Organizational Design and Restructuring in Response to Crises: Lessons from Computational Modeling and Real-World Cases
Authors: Lin Zhiang (John) , Zhao Xia , Ismail Kiran M. , Carley Kathleen M.
Published: September 2006

Organizations are occasionally faced with technology-based and accident-triggered crises that may cause costly disasters if not handled properly. Questions arise: How should organizations, with their complex processes and human involvement, be designed if they are to perform well in such crises? Would organizations benefit from structural changes during crises? From a neo-information processing perspective that views organizations as composed of cognitively restricted, socially situated, and task-oriented actors, we argue that the causes and consequences of crises may be better understood through the systematic examination of both environmental and organizational factors. We address our research questions using a rather unique approach: a matched analysis of 80 real organizational cases and 80 computer-simulated organizations. The findings show that a crisis can present critical challenges to organizational performance both externally and internally, and that there is no design guarantee that a high-performing organization will continue to perform well during a crisis situation. In addition, when organizations restructure to adapt to crisis situations, they often face the serious challenges of having to understand not only the external environment, but also organizational design traps.
Management of juvenile laryngeal papilloma: Further observations
Authors: Gross Charles W. , Hubbard Ron
Published: September 2006

Twenty‐two patients with juvenile laryngeal papillomatosis were treated over a five‐year period at The University of Tennessee, using a combination of microsurgical removal and administration of autogenous papilloma vaccine. Twelve patients were classified as having a favorable result. Six were improved, and three were unimproved; one patient was lost to follow‐up. Nine patients have been free of disease for greater than one year. Histologic differences in papillomata removed from patients before and after treatment with the vaccine are reported as are the results of studies attempting to show immunologic response by the gel diffusion and lymphocytic transformation techniques. No conclusions are made as a result of the histologic and immunologic studies. There were no treatment controls other than the response of the individual patient; therefore, no definite conclusions are made concerning this mode of therapy. It is suggested that the results of this clinical study are such that they would tend to indicate that this is a most useful treatment regime.
Adenotonsillectomy as the treatment of serious medical conditions: Five case reports
Authors: Jaffee I. Sidney
Published: September 2006

Adenotonsillectomy surgery for serious medical conditions has been reported in various specialty medical journals in recent years. Most of these reported cases were performed for cor pulmonale and resultant congestive heart failure.

I have had personal experience with adenotonsillectomy, or just adenoidectomy as treatment for not only cases of cor pulmonale, but also acute upper airway obstruction and recurrent lower respiratory disease apparently resulting from the severe upper airway obstruction.

Following hospital consultation for five children who had been hospitalized as medical emergencies because of severe cardiac or pulmonary disease, recommended surgery was performed only after emergency medical treatment had been instituted. These cases were all performed within a two‐week period following hospitalization. The average follow‐up of these youngsters has been two years. To date there have been no further severe medical problems in any of these children.

It is my feeling that many youngsters seen in consultation have less severe manifestations of these severe obstructive conditions. This is probably the reason that following adenotonsillectomy in selective cases there occurs a period of rapid growth and development.
Abscesses of the head and neck
Authors: Sprinkle Philip M. , Veltri Robert W. , Kantor Linda M.
Published: September 2006

Staphylococcus aureus and pathogenic streptococci are commonly associated with abscess formations of the head and neck. Anaerobic bacteria, primarily Bacteroidaceae are commonly present in abscess formation of the head and neck. Anaerobic infections have not been considered to the extent their presence indicated. Appropriate antibiotic therapy, currently Clindamycin, is usually straightforward, but resistance may develop, making the individual case more difficult. Anaerobic infections should be considered whenever a foul smelling abscess occurs. A Gram stained smear of the pus may reveal pleomorphic Gram‐negative bacteria. Treatment of an abscess includes in addition to the antibiotic therapy surgical incision and drainage of purulent collections, open treatment of infected wounds, maitenance of fluids, hemoglobin and nutrition.
Acoustic neurinomas presenting as middle ear tumors
Authors: Storrs Lloyd A.
Published: September 2006

Since the advent of the widespread use of the operating microscope and the excellent graduate and post‐graduate training in otology, more and more otosurgeons are exploring disease of the middle and inner ear; consequently, more and more unusual and varied anomalies and tumors are being described. This paper describes the unusual presentation of acoustic neurinomas in the middle ear.

Most acoustic nerve tumors arise within the meatus of the internal auditory canal, producing the syndrome of the cerebellopontine angle.

In the first case presented, the tumor did not arise in the usual location, and this points out the fact that acoustic nerve tumors may arise anywhere along the course of the VIIIth nerve. It is felt that the tumor must have arisen in one of the smaller branches of the inferior vestibular nerve, lateral to the vestibule, as it did not extend medially beyond the medial wall of the vestibule. Instead, it presented in the cochlear windows as a middle ear tumor.

In the second case, the tumor apparently arose in the usual location, in the meatus of the internal auditory canal. Its lateral extension was unusual, in that the tumor filled the entire labyrinth and presented as a middle ear tumor in the cochlear windows of the middle ear, and its extension medially, produced the classical findings of the cerebellopontine angle tumor.
Middle and inner ear anomalies in a conjoined twin
Authors: Igarashi Makoto , Singer Donald B. , Alford Bobby R. , Cook Ted A.
Published: September 2006

A pair of temporal bones obtained from a thoracopagus conjoined twin revealed malformation of the facial nerve and vestibular fenestra (oval window) on one side, and underdeveloped petrous bone and aplastic inner ear apparatus on the other.
Oval window absence, bony closure of round window, and inner ear anomaly
Authors: Adkins Warren Y. , Gussen Ruth
Published: September 2006

Unusual temporal bone findings are presented in a seven‐and‐one‐half‐year‐old female with marked hearing impairment and multiple congenital anomalies. The oval window was absent bilaterally, with no stapedio‐vestibular joint development on the right side and incomplete development on the left side. The round window membranes were normal, but on the left side the round window niche was walled off from the middle ear by bone continuous with the periosteum of the middle ear surface of the otic capsule. Surgically, this would have been interpreted as congenital absence of the round and oval windows. It should be recognized that the round window membrane may be present in the absence of an open round window niche. Bilaterally the cochlea consisted of 13/4 turns, and on the left side, the scalae tympani ended blindly in the second turn so that no helicotrema was present. Spiral ganglion cells were markedly reduced on the right side and entirely absent on the left, where there was marked thickening of the cribriform base of the cochlea. The organ of Corti was present in all turns. The bony semicircular canals were not formed.

The embryological development and interference with development which probably resulted in these malformations are discussed.

Oval window absence or congenital footplate fixation should probably be referred to as varying degrees of stapediovestibular joint malformation.
Horizontal tongue flap in repair of tonsillar palatal defect
Authors: Adkins Warren Y. , Putney F. Johnson
Published: September 2006

Local tissue, when available, seems superior to utilizing distant tissue for reconstruction of the tonsillar fossa region. Repair of the defect employing a horizontal posteriorly based tongue flap has been useful. It has the advantage of minimal decrease in the remaining tongue bulk and mobility, requires only 90 rotation, and can be used after radiation therapy or ligation of the ipsilateral lingual artery.
Intact canal wall tympanoplasty in the management of cholesteatoma
Authors: Glasscock III Michael E. , Miller Gale W.
Published: September 2006

There are presently two schools of thought on the proper surgical management of cholesteatoma associated with chronic ear disease: one feels that the ear should be exteriorized and left “open”; the other takes the position that the disease can be removed, and the ear left in its normal anatomical and functional state. The latter group are known to favor a “closed” or more conservative procedure. The purpose of this paper is to review a, series of patients who have had cholesteatoma managed by an intact canal Avail procedure that prevents a postoperative cavity.

Out of a series of 590 chronic ear surgeries performed between January 1, 1970, and December 31, 1974, there were 179 done for cholesteatoma (30 percent). There were 153 patients, 26 of whom had bilateral disease. Twenty‐three patients were lost to folloAV‐up, giving an overall total of 154 surgeries with from one to five‐year information. The overall follow‐up rate was 85 percent.

Recurrent cholesteatoma was the most bothersome complication and occurred in 14 percent of the series. Residual cholesteatoma was managed by doing all procedures in two stages.

The authors feel that the intact canal wall tympanoplasty is a procedure that will gain acceptance and will be more widely used in the future.
Co2 laser laryngoscopy in a variety of lesions
Authors: Lyons George D. , Lousteau Ray J. , Mouney Daniel F.
Published: September 2006

We have had the opportunity to employ the CO, surgical laser with suspension laryngoscopy and microscopic adaptations to treat a variety of laryngeal conditions over two years. Each type of laryngeal condition is discussed, and the benefits of laser management is evaluated. This type of laryngeal management is compared with other forms of treatment such as the standard surgical approaches, electrocautery, and cryosurgery.
Glomus jugulare tumors of the middle ear and mastoid: Diagnosis and surgical treatment
Authors: Fernandez‐Blasini Nelson
Published: September 2006

At the 1976 Southern Sectional Meeting of American Laryngological, Rhinological and Otological Society, Inc., a color movie presenting two cases on the “diagnosis and treatment of glomus jugulare tumors of the middle ear and mastoid” was shown. The purpose of this paper and film is to describe the author's experience of 16 cases of glomus tumors involving the middle ear and mastoid (seven tympanicum and nine jugulare). A review of the literature and findings pertaining specifically to the two cases shown in the film is presented.
Temporal bone findings in pierre robin syndrome
Authors: Igarashi Makoto , Filippone Marion V. , Alford Bobby R.
Published: September 2006

This is the first complete report on the histopathologic study of the temporal bones from an infant with a well‐documented Pierre Robin syndrome (micrognathia, glossoptosis and cleft palate), demonstrating multiple middle and inner ear anomalies. The anomalies are basically architectural malformations rather than neural or end organ developmental anomalies. The anomalies in this case, except for a few points, are somewhat similar in both ears. Multiple anomalies include: abnormal narrowing of the cms commune‐utricle junction, superiorly located cms commune and posterior semicircular canal, underdeveloped modiolus, absence of the bony septum between the middle and apical coil (existence of scala communis in left ear), abnormally small internal auditory meatus, and abnormal direction of internal auditory canal, large cartilaginous mass around the superior semicircular canal and in the tympanic end of the fissula ante fenestram, small facial nerve, large facial bony canal dehiscence, anomalic stapes, etc.
Auditory thresholds in the guinea pig: A preliminary report of a behavioral technique employing a food reward
Authors: Walloch Richard A. , Taylor‐Spikes Margaret
Published: September 2006

Guinea pigs have been trained to press a lever for a food reward. Then the behavior was used to obtain the auditory thresholds for six guinea pigs. The thresholds obtained in the present study agree with those previously obtained by Heffner, et al. The most important aspect of the training process Was the habituation of the guinea pigs. Once the guinea pig was accustomed to the food and training cage, he could be trained in a manner similar to that used to train many other species.
Metastasis of malignant melanoma of the nasal mucosa to the small intestine
Authors: Helidonis Emmanuel S. , Myers Eugene N. , Barnes E. L.
Published: September 2006

Malignant melanoma of the mucous membranes is rare and has a very poor prognosis. When localized in the nose, the tumor becomes apparent late in the course of the disease with nasal obstruction and epistaxis. Distant metastases are uncommon, but any organ of the body can be involved. A case of a malignant melanoma of the nasal mucosa with metastasis to the small intestine is presented, and the natural history of the metastatic disease is discussed.
The lower blepharoplasty
Authors: Bernstein Leslie
Published: September 2006

The day prior to the operation, or preferably on the morning of surgery, the patient is reexamined in the sitting position and, at that time, determinations are made regarding the placement of the incision and whether any fat should be removed.

The author does the operation only under local anesthesia, and the patient is invariably admitted to the hospital, at least postoperatively. The patient is instructed to remove all make‐up the evening before and to wash her face with an antiseptic soap. A sedative, such as Nembutal, mg 100‐150, is always given to the patient one‐half hour before retiring, to permit a good night's sleep. A well‐rested patient has a higher pain threshold and tolerates the surgical procedure much better emotionally.

On call to the operating room, the patient is premedicated with Demerol and Nembutal, mg 100 each, I.M., and an intravenous transfusion of 5 percent dextrose in water is commenced. Should it become necessary, a “piggyback” transfusion is added to the I.V. This consists of 250 cc of 5 percent dextrose in water to which are added 100 mg of Demerol. The Demerol solution may then be titrated during the operation, the rate usually ranging from four to 20 drops per minute.
Bestimmung der Objektform durch Bildanalyse der Oberflächentextur (Shape from Texture)
Authors: Greiner Thomas , Das Sukhendu
Published: September 2006

In diesem Beitrag wird ein neues Verfahren vorgestellt, das es ermöglicht, die 3D-Objektform durch Analyse der 2D-Abbildung der texturierten Objektoberfläche darzustellen. Der englische Fachbegriff hierzu lautet “Shape from Texture”. Das beschriebene Verfahren setzt eine M-Kanal Waveletfilterbank zur Merkmalsgewinnung ein. Theoretische Ableitungen der geometrischen Verhältnisse in einem Polarkoordinatensystem werden für eine mit einem Sinusmuster versehene geneigte ebene Fläche hergeleitet. Bei der Auswertung realer Bilddaten zeigt sich, dass dieses Verfahren auch für andere geometrische Formen genutzt werden kann. Weiterhin wird gezeigt, wie es mittels des Texturgradienten, der ein Maß für die geometrische Veränderung der Textur ist, möglich wird, Abbildungen von 3D-Objekten zu segmentieren bzw. Tiefenveränderungen zu erkennen.
Robust PID-Controller Design Meeting Pole Location and Gain/Phase Margin Requirements for Time Delay Systems (Entwurf robuster PID-Regler mit Anforderungen an die Pollagen und an die Amplituden-/Phasenreserve für Totzeitsysteme)
Authors: Hohenbichler Norbert , Abel Dirk
Published: September 2006

A robust PID tuning method based on the parameter space approach is presented. In two steps a robust PID controller setting is designed which simultaneously satisfies pole location and gain/phase margin criteria. The plant model may be an arbitrary LTI time delay system with uncertain parameters (including the time delay), which are restricted by an operation domain.
Menge aller robust stabilisierenden PID-Regler: Methodik und Software (Teil III) (The Set of All Robust Stabilizing PID Controllers: Methods and Software (Part III))
Authors: Bajcinca Naim , Hulin Thomas
Published: September 2006

In diesem Beitrag wird die Matlab Toolbox ROBSIN vorgestellt, die sich für die schnelle Berechnung eines optimalen robusten PID-Reglers für zeitkontinuierliche, zeitdiskrete und totzeitbehaftete Systeme eignet. Dieses Werkzeug automatisiert die Algorithmen, die bereits in den zwei erschienenen Teilen dieser Beitragsreihe vorgestellt wurden. ROBSIN kann von http://www.robotic.dlr.de/robsin heruntergeladen werden.
Die Ankopplung verschiedenartiger Detektionssysteme für dimensionelle Messungen im Mikro- und Nanometerbereich an die Nanomessmaschine (Linking up Various Detection Systems for Dimensional Measurements in the Micro- and Nanorange with the Nanomeasuring Machine)
Authors: Dai Gaoliang , Pohlenz Frank , Danzebrink H.-U.
Published: September 2006

Die zunehmende Miniaturisierung von Bauteilen in der Halbleiter- und Mikrosystemtechnik stellt gehobene Anforderungen an die im Rahmen der Qualitätssicherung verwendeten Messsysteme. Besonderes Augenmerk muss hierbei auf die Vergleichbarkeit der Messergebnisse und ihre Rückführbarkeit gelegt werden. In diesem Beitrag wird ein Messgerät vorgestellt, das auf Basis des hochauflösenden Positioniersystems der “Nanomessmaschine” arbeitet. Durch die geeignete Wahl eines von vier taktilen und optischen Antastsystemen kann dieses System für die unterschiedlichen Messaufgaben in der dimensionellen Messtechnik im Mikro- und Nanometerbereich angepasst werden. Eine Auswahl von Kalibrierergebnissen illustriert die Möglichkeiten des Messsystems.
Insulin and glucose mediate opposite intracellular ionized magnesium variations in human lymphocytes
Authors: Delva P , Degan M , Trettene M , Lechi A
Published: September 2006

Insulin is capable of increasing intracellular magnesium, although very little is known about the effect of insulin on the biologically active fraction of magnesium, i.e. the ionized quota (Mgi2+), its interactions with glucose, and the cellular mechanisms involved in these processes. We studied the interactions of the effects of insulin and glucose on intracellular ionized magnesium in human lymphocytes. Mgi2+ was measured using a fluorimetric method and the Mg2+-sensitive dye, furaptra. We found that insulin significantly increases the Mgi2+(without insulin 227 ± 14 μM, with 10 μU/ml, insulin 301 ± 30 μM, P<0.0001, n = 12) in a dose-dependent manner in all three glucose concentrations tested (5, 7 and 15 mmol/l). The half-maximal effect of insulin was approximately 0.8 μU/ml. Glucose and insulin showed opposite effects in their ability to modify Mgi2+ in lymphocytes. Inhibitors of the membrane Na+- Mg2+ transport system and of phosphatidylinositol (PI) 3-kinase abolish the insulin-mediated increase of Mgi2+, thus suggesting that insulin is capable of increasing Mgi2+ by modulating the activity of this transport system, possibly through the mediation of PI 3-kinase activation. Taking into account the relationship between insulin and glucose plasma levels and their opposing effects on Mgi2+, this mechanism may represent the two limbs of a biphasic regulatory system of Mgi2+ in both physiological and pathological conditions.
Direct and indirect effects of insulin on hepatic glucose production in diabetic depancreatized dogs during euglycemia
Authors: Gupta Neehar , Park Edward , Sandhu Harmanjit , Goh Tracy , Tchipashvili Vaja , Giacca Adria
Published: September 2006

Insulin suppresses glucose production (GP) via both extrahepatic (indirect) and hepatic (direct) effects. We have shown that the direct effect, undetectable in moderately hyperglycemic diabetic dogs, is restored by insulin-induced euglycemia. The first aim of the present study was to determine whether euglycemia per se, and not the excess insulin needed to obtain it, restores the direct effect of insulin on GP. Basal insulin was given portally in depancreatized dogs to attain only moderate hyperglycemia, then an additional insulin was given portally or peripherally to match the peripheral insulin levels and thus to obtain a greater hepatic insulinization with portal delivery. Plasma glucose was allowed to fall to euglycemia before a euglycemic clamp was performed. During euglycemia, there was a tendency (P=0.075) for greater suppression of GP by portal than peripheral insulin. Also, there was a significantly different effect of time (P=0.01) on GP in the two groups, with greater suppression over time in the portal group. The second aim was to test the hypothesis that because of inadequate hepatic insulinization and consequent lack of direct inhibition of GP, peripheral insulin replacement requires peripheral hyperinsulinemia to achieve euglycemia. Portal or peripheral insulin was given to achieve euglycemia and basal GP, and insulin levels were measured. More peripheral insulinemia was required with peripheral than portal insulin replacement to maintain similar euglycemia and GP. Our conclusions are as follows: (1) euglycemia per se is sufficient to acutely restore the direct effect of insulin on GP and (2) at euglycemia, peripheral replacement of insulin, as in insulin-treated diabetes, results in peripheral hyperinsulinemia but unchanged basal GP.
Circulating hormones and hypothalamic energy balance: regulatory gene expression in the Lou/C and Wistar rats
Authors: Mitchell Sharon E , Nogueiras Ruben , Rance Kellie , Rayner D Vernon , Wood Sharon , Dieguez Carlos , Williams Lynda M
Published: September 2006

To ascertain the mechanisms underlying low caloric intake and low body weight in the Lou/C rat, the circulating hormone levels and gene expression of hypothalamic peptides and receptors important in energy balance and the induction of suppressor of cytokine signalling 3 (SOCS3) gene expression in response to leptin challenge were compared with Wistar rats. Plasma leptin levels were lower in the Lou/C rat, as were levels of rat corticosterone, TSH and T4 but not T3. Ghrelin levels were higher in the Lou/C rat. Total leptin receptor (Ob-R) and the long form of the leptin receptor (Ob-Rb) gene expression were lower in the arcuate (ARC) and ventromedial nuclei (VMN) in Lou/C rat. Ghrelin receptor expression in the ARC and VMN was lower in Lou/C than in Wistar rats. However, agouti gene-related peptide (AgRP) and neuropeptide Y (NPY) gene expression were higher in the Lou/C rat. There was no difference in the level of cocaine- and amphetamine-regulated transcript gene expression in the ARC, but both were higher in the paraventricular nuclei of the Lou/C breed. There was no difference in Ob-R gene expression in, or [125I]leptin binding to, the choroid plexus. SOCS3 mRNA induction in response to leptin was lower in the Lou/C rat. This study reveals that the comparatively low plasma leptin, TSH and T4 levels, and high ghrelin levels together with high levels of AgRP and NPY gene expression seen in the Lou/C rat are indicative of a strong drive to eat and decreased energy expenditure, which are in direct opposition to the comparatively low body weight and adiposity of this rat strain.
The endocrine disrupting chemical, diethylhexyl phthalate, activates MDR1 gene expression in human colon cancer LS174T cells
Authors: Takeshita Akira , Inagaki Keiji , Igarashi-Migitaka Junko , Ozawa Yasunori , Koibuchi Noriyuki
Published: September 2006

Resistance to anticancer drugs is often mediated by the overexpression of P-glycoprotein encoded by the multi-drug resistance (MDR1) gene. The nuclear receptor, steroid and xenobiotic receptor (SXR), is one of the key transcriptional regulators of MDR1 gene expression. A variety of xenobiotics bind to SXR, and stimulate transcription on xenobiotic-response elements (XREs), located in the MDR1 gene promoter. Diethylhexyl phthalate (DEHP) is widely used as a plasticizer for polyvinyl chloride (PVC) medical devices. Previous studies have shown that a significant amount of DEHP leaches from PVC infusion bags and lines during interventions, such as total parenteral nutrition, blood transfusion, and cancer chemotherapy. Thus, the leaching of DEHP during parenteral chemotherapy for cancer patients may facilitate MDR1 expression in various tissues, including cancer cells, which may promote drug resistance. To examine such a hypothesis, the effect of DEHP on SXR-mediated transcription of the MDR1 gene was studied in the human colon adenocarcinoma-derived cell line, LS174T cells, which endogenously express SXR. DEHP increased the SXR-mediated transcription of the MDR1 gene in luciferase-reporter assays. The induction by DEHP was abrogated when a reporter plasmid containing mutated DR+4 motif in the XRE was used. In a mammalian two-hybrid assay, DEHP recruited steroid receptor co-activator-1 to the ligand-binding domain of SXR. Finally, using real-time reverse transcriptase-PCR, we showed that DEHP increased MDR1 gene expression in a dose-dependent manner. We conclude that DEHP is an inducer of the MDR1 gene in this cell line. As such, the leaching of DEHP from the PVC medical devices may influence the MDR1 expression, which may induce resistance to drugs in certain populations of cancer cells.
Plasma profiles of adrenocorticotropic hormone, cortisol, α-melanocyte-stimulating hormone, and growth hormone in dogs with pituitary-dependent hyperadrenocorticism before and after hypophysectomy
Authors: Hanson J M , Kooistra H S , Mol J A , Teske E , Meij B P
Published: September 2006

The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, α-melanocyte-stimulating hormone (α-MSH), and GH were studied in 17 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy. The aim of the study was to investigate the relation between the hormone profile characteristics and recurrence of PDH after surgery.

The hormones were secreted in a pulsatile fashion. The basal plasma cortisol concentration and area under the curve (AUC) for cortisol were significantly higher in the PDH cases than in eight controls. The characteristics of the plasma profiles of ACTH and α-MSH were not significantly different between the PDH cases and the controls. In the PDH cases, less GH was secreted in pulses than in the controls, but the difference was not significant. The basal plasma cortisol concentration, the AUC for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased significantly after hypophysectomy for the group of PDH cases. The basal plasma concentrations of ACTH and α-MSH, the AUC for α-MSH, and the characteristics of the plasma GH profiles of the PDH cases remained unchanged after hypophysectomy. No pulses of α-MSH were observed after hypophysectomy. The co-occurrence between the ACTH and cortisol pulses decreased significantly with hypophysectomy. The postoperative pulse frequency of ACTH was the only characteristic with predictive value for the recurrence of PDH after hypophysectomy.

The results of this study demonstrate that ACTH, cortisol, α-MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy effectively reduces the secretion of ACTH and cortisol. The presence of ACTH pulses after hypophysectomy is a risk factor for the recurrence of hyperadrenocorticism.
Region-specific expression of androgen and growth factor pathway genes in the rat epididymis and the effects of dual 5α-reductase inhibition
Authors: Henderson Natali Anne , Cooke Gerard M , Robaire Bernard
Published: September 2006

Dihydrotestosterone (DHT) is the primary androgen acting in the epididymis, the site of sperm maturation. Previously, we showed that the treatment of male rats with PNU157706, an inhibitor that acts on both isoforms of 5α-reductase to prevent DHT formation, has effects on the expression of genes implicated in processes that create the optimal luminal microenvironment required for sperm maturation, and on sperm maturation itself. However, signaling pathways involved in regulating or mediating DHT actions in the epididymis remain largely unknown. The goals of this study were to determine the expression profiles of potential signaling systems in the epididymis and assess their DHT-dependence using two different dual 5α-reductase inhibitors. Rats were untreated or gavaged with vehicle, 10 mg/kg per day PNU157706 or 32 mg/kg per day FK143 for 28 days and epididymal gene expression was analyzed. Gene array analysis revealed analogous effects of FK143 on overall epididymal gene expression when compared with previous PNU157706 studies. Quantitative RT-PCR analysis of the expression of the 5α-reductase isozymes, androgen receptor, and members of the IGF, FGF, TGF, and VEGF families revealed novel region-specific expression profiles in the epididymis that were differentially affected by 5α-reductase inhibition; the two inhibitors had parallel effects. Specifically, in proximal regions, 5α-reductase 1, androgen receptor, and TGF-β1 expression increased after treatment, while in distal regions expression of IGF-I, IGFBP-5, IGFBP-6, and FGF-10 decreased. These results provide insight into epididymal signaling mechanisms and indicate potential candidates acting either upstream or downstream of DHT to regulate and/or mediate its actions in the epididymis.
Cyclic changes in the vaginal epithelium of normal rhesus macaques
Authors: Poonia B , Walter L , Dufour J , Harrison R , Marx P A , Veazey R S
Published: September 2006

Studies in nonhuman primates indicate that changes in the thickness and integrity of the vaginal epithelium affect the transmission rates of HIV-1, but few studies have examined the normal variations that may occur in the vagina of normal macaques as a result of aging or changes in the menstrual cycle. This study was conducted to determine if differences occur in the thickness of the vaginal mucosa with age or menses. Vaginal mucosal thickness was compared in 46 rhesus macaques grouped as juvenile (1–3 years old), mature cycling (3–21 years old), and geriatric (> 21 years old). Epithelia of mature cycling macaques were also compared at different stages of the menstrual cycle. Older females (> 21 years) had the thinnest and least keratinized epithelium of all groups, followed by the youngest females (< 3 years). The vaginal epithelium was also thinner in cycling macaques during menses compared to the follicular stage. In addition, young, geriatric, or cycling macaques during menses had minimal keratinization. We hypothesize that normal physiologic changes in the vaginal epithelium of women occur with age and menses, which may affect a woman’s susceptibility to HIV-1 transmission and other sexually transmitted diseases. Also, age and menstrual cycle should be considered when designing vaginal transmission experiments in rhesus macaques.
Orchidectomy increases expression and activity of Cu/Zn-superoxide dismutase, while decreasing endothelial nitric oxide bioavailability
Authors: Blanco-Rivero Javier , Sagredo Ana , Balfagón Gloria , Ferrer Mercedes
Published: September 2006

This study examines the effect of male sex hormones on the release, metabolism and function of endothelial nitric oxide (eNO) in rat aorta. Aortic segments from orchidectomized and control male Sprague–Dawley rats were used to measure eNO synthase (eNOS) expression, nitric oxide (NO) release, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced relaxation and Cu/Zn-superoxide dismutase (SOD) expression and activity. eNOS expression as well as basal and ACh-induced NO release were similar in arteries from both groups of rats. Basal superoxide anion production was similar in arteries from both groups, while ACh-induced superoxide anion formation was greater in arteries from orchidectomized than control rats. Orchidectomy increased the vasodilator effect induced by ACh, but did not alter that induced by SNP. SOD, a superoxide anion scavenger, did not modify the SNP-induced relaxation in aortas from control or orchidectomized rats. The membrane-permeable mimetic of SOD, tempol, increased the SNP-induced relaxation more in aortas from orchidectomized than control rats. The effect of endogenous SOD inhibitor, diethyl-dithiocarbamate, reduced the relaxation induced by SNP in segments from both groups of rats. The expression and activity of Cu/Zn-SOD were greater in aortas from orchidectomized than control rats. These data show that endogenous male sex hormone deprivation altered neither eNOS expression nor eNO release, while it increased the expression and activity of Cu/Zn-SOD. However, the predominant vascular effect of orchidectomy is to increase NO metabolism.
Nitric oxide inhibits, and carbon monoxide activates, islet acid α-glucoside hydrolase activities in parallel with glucose-stimulated insulin secretion
Authors: Mosén Henrik , Salehi Albert , Henningsson Ragnar , Lundquist Ingmar
Published: September 2006

We have studied the influence of nitric oxide (NO) and carbon monoxide (CO), putative messenger molecules in the brain as well as in the islets of Langerhans, on glucose-stimulated insulin secretion and on the activities of the acid α-glucoside hydrolases, enzymes which we previously have shown to be implicated in the insulin release process. We have shown here that exogenous NO gas inhibits, while CO gas amplifies glucose-stimulated insulin secretion in intact mouse islets concomitant with a marked inhibition (NO) and a marked activation (CO) of the activities of the lysosomal/vacuolar enzymes acid glucan-1,4-α-glucosidase and acid α-glucosidase (acid α-glucoside hydrolases). Furthermore, CO dose-dependently potentiated glucose-stimulated insulin secretion in the range 0.1–1000 μM. In intact islets, the heme oxygenase substrate hemin markedly amplified glucose-stimulated insulin release, an effect which was accompanied by an increased activity of the acid α-glucoside hydrolases. These effects were partially suppressed by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. Hemin also inhibited inducible NO synthase (iNOS)-derived NO production probably through a direct effect of CO on the NOS enzyme. Further, exogenous CO raised the content of both cGMP and cAMP in parallel with a marked amplification of glucose-stimulated insulin release, while exogenous NO suppressed insulin release and cAMP, leaving cGMP unaffected. Emiglitate, a selective inhibitor of α-glucoside hydrolase activities, was able to markedly inhibit the stimulatory effect of exogenous CO on both glucose-stimulated insulin secretion and the activityof acid glucan-1,4-α-glucosidase and acid α-glucosidase, while no appreciable effect on the activities of other lysosomal enzyme activities measured was found. We propose that CO and NO, both produced in significant quantities in the islets of Langerhans, have interacting regulatory roles on glucose-stimulated insulin secretion. This regulation is, at least in part, transduced through the activity of cGMP and the lysosomal/vacuolar system and the associated acid α-glucoside hydrolases, but probably also through a direct effect on the cAMP system.