bluuebunny/crossref_metadata_2025 huggingface dataset:
NT-proANP and BNP in Renovascular and in Severe and Mild Essential Hypertension
Authors: Mussalo Hanna , Vanninen Esko , Ikäheimo Risto , Hartikainen Juha
Published: April 2003

Background/Aims: The plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) become increased in hypertension. However, it is unknown what is the effect of the etiology and the severity of hypertension on the plasma concentrations of ANP and BNP. Methods: We examined plasma levels of ANP (measured as N-terminal fragment of proatrial natriuretic peptide; NT-proANP) and BNP in patients having sustained hypertension of different etiology and severity: in patients with renovascular hypertension (RVHT, n = 12), severe essential hypertension (SEHT, n = 37), and mild essential hypertension (MEHT, n = 29). In addition, we studied the diagnostic value of NT-proANP and BNP to discriminate patients with RVHT from patients with essential hypertension. Results: The plasma concentrations of NT-proANP and BNP were higher in the RVHT group (593 ± 80 and 25.0 ± 9.3 pmol/l, respectively) than in the SEHT group (320 ± 33 and 4.7 + 0.6 pmol/l, respectively; p < 0.001 for both), in spite of the similar blood pressure level, and also higher than in the MEHT group (356 ± 30 and 7.0 ± 1.0 pmol/l; p = 0.004 and p = 0.006, respectively). There was no difference in natriuretic peptide levels between the SEHT and MEHT groups. Plasma NT-proANP and BNP correlated positively with aging and serum creatinine concentration and inversely with left ventricular diastolic filling. In addition, NT-proANP correlated positively with systolic blood pressure and BNP with left ventricular mass index. The areas under receiver operating characteristic curves for plasma NT-proANP and BNP to discriminate RVHT patients from patients with essential hypertension were 0.793 and 0.782, respectively. The best cutoff value was 530 pmol/l for NT-proANP, giving a sensitivity of 67% with a specificity of 86%. The cutoff value of 9.8 pmol/l for BNP resulted in a sensitivity of 58% and a specificity of 90%. Conclusions: Patients with RVHT have higher plasma levels of NT-proANP and BNP than patients with essential hypertension. In addition to the etiology of hypertension, also left ventricular characteristics are important determinants of NT-proANP and BNP concentrations in hypertension. Due to the low sensitivity, NT-proANP and BNP are not suitable as screening tools for RVHT.
IL-13 Is More Efficient than IL-4 for Recruiting Langerhans Cell Precursors from Peripheral CD14+ Monocytes
Authors: Bechetoille Nicolas , Valladeau Jenny , Geissmann Frédéric , Dumont Sandy , Maréchal Sylvie , Gofflo Sandrine , André Valérie , Schmitt Daniel , Perrier Eric , Dezutter-Dambuyant Colette
Published: April 2003

Background: GM-CSF, IL-4 and TGF-β1 can drive the differentiation of CD14+ monocytes towards the immature Langerhans (LC) dendritic cell (DC) pathway. Their in vivo epidermal LC counterparts are mainly identified by the langerin molecules which are cross-linked into Birbeck granules (BG) upon mannose residue activation. Objective: The IL-13 and IL-14 cytokines sharing similar anti-inflammatory/immune functions, we investigated whether IL-13 (plus GM-CSF/TGF-β1) can substitute for IL-4 to preferentially skew the CD14+ monocyte differentiation towards LC. Methods: CD14+ monocytes cultured in the presence of GM-CSF/TGF-β1/IL-13 (IL-13-DC) for 6 days were then compared to GM-CSF/TGF-β1/IL-4-generated LC (IL-4-DC) by studying their phenotype, ultrastructural and functional features. Results: IL-13, in synergy with GM-CSF/TGF-β1, induced CD14+ monocytes to differentiate into LC after a short TNF-α stimulation more efficiently than IL-4. IL-13-DC are more immature than IL- 4-DC, as shown by both their preserved expression of monocyte markers (CD14, CD68) and their strong capacity of FITC-dextran uptake. Conclusion: IL-13 in combination with GM-CSF/TGF-β1/TNF-α favors CD14+ monocyte differentiation into LC which display numerous BG.
Are There Any Differences in Skin Barrier Function, Integrity and Skin Blood Flow between Different Subpopulations of Asians and Caucasians?
Authors: Yosipovitch G. , Goon A.T.J. , Chan Y.H. , Goh C.L.
Published: April 2003

Background: There are few studies with a limited number of subjects examining whether there are population differences in skin barrier function between Asian skin and Caucasian skin. Objectives: To study skin barrier function and integrity in different subpopulations of Asian skin: Chinese, Malay, Indian and Caucasian. Methods: Transepidermal water loss (TEWL) and laser Doppler perfusion imaging (LDPI) were measured at baseline, after tape stripping and during recovery 3 h after stripping. Barrier integrity was assessed by counting the number of tape strippings required to cause an average TEWL of 20 g/m2/h. Results:  There was no statistically significant difference in basal, poststripping and 3-hour recovery TEWL and LDPI readings between the 4 ethnic groups. Neither was there any statistically significant difference in recovery rate of TEWL and LDPI reading after tape stripping. There was also no difference in barrier integrity between the ethnic groups. All parameters did not differ when skin type was analyzed. Females had a better skin integrity; however, the barrier repair was similar. Conclusion: There is no evidence to support any real difference in skin barrier function between the 4 ethnic groups and the different skin types. Females seem to have a better integrity than males.
Influence of the Galenic Form of a Skin-Protective Preparation on the Application Pattern Assessed by a Fluorescence Method
Authors: Bankova L. , Lindenau S. , Fuchs S. , Tittelbach J. , Fischer T.W. , Elsner P.
Published: April 2003

The efficacy of skin-protective preparations is still under debate. One aspect of efficient skin protection is dependent on the quality of application concerning the homogenous distribution of the skin-protective products. The periungual areas, the finger webs and tips are known to be frequently incompletely covered when a protective cream is applied. In a randomized study, a protective mousse and a standard commercially available protective cream were compared regarding their application adequacy and cosmetic acceptance. Thus, 2 groups of 50 subjects with healthy skin were recruited for a typical application of the cream or the mousse. Distribution was examined under long-wave UV light. Additionally, the cosmetic acceptance of both products was studied by means of a questionnaire. Results showed significant differences between the mousse and the cream. The mousse proved better coverage, particularly in the problem fields. Our results showed that a mousse can offer advantages in skin protection by virtue of its better distribution and acceptance.
Wear Behaviour of Silicon Carbide/Electroless Nickel Composite Coatings at High Temperature
Authors: Staia M. H. , Conzoño A. , Cruz M. R. , Roman A. , Lesage J. , Chicot D. , Mesmacque G.
Published: April 2003

The present paper reports the results obtained from sliding wear tests performed at both room temperature and high temperature (100 and 300°C) on silicon carbide/nickel composite coatings annealed at 400°C in argon. The coatings were deposited industrially on AISI 1020 steel discs by using a proprietary self catalysing chemical reduction process (Hardex). The tests were conducted without lubrication in argon, employing a ball on disc tribometer. A load of 5 N was used at a constant sliding speed of 0·1 ms-1. The mating pair was an alumina ball of 6 mm diameter. For the tests performed at 25°C, the effect of heat treatment contributed to an improvement in the coating wear resistance of nearly 135%, when compared to the as deposited conditions. It was determined that the set of the experimental conditions for the wear test performed at high temperature, i.e. the load used, the nature of the mating surface, and the low velocity of the test, added to a small coating thickness to particle size ratio, created very severe conditions, which caused coating removal. Wear rates nearly 23 and 11·6 times larger were obtained for the heat treated coatings tested at 100 and 300°C, respectively when compared with the wear resistance of the heat treated coatings tested at 25°C.
MECHANICAL AND CHEMICAL PROPERTIES OF LOW TEMPERATURE PLASMA SURFACE ALLOYED 316 AUSTENITIC STAINLESS STEEL
Authors: Thaiwatthana S. , Li X. Y. , Dong H. , Bell T.
Published: April 2003

Low temperature plasma nitriding and carburising are well known as methods for improving tribological properties without deterioration of corrosion properties of austenitic stainless steels. ‘S phase’ is a key alloyed layer, achieved from these two plasma thermochemical processes, referred as nitrogen and carbon S phase, respectively. The present work has been focused on full characterisation of the mechanical and chemical properties of carbon and nitrogen S phase on austenitic stainless steel AISI 316 produced during low temperature plasma processes with different process parameters. A series of theoretical, experimental, and analytical studies have been conducted in order to lay the necessary foundations for fully realising application potential of these processes in various stress and environmental conditions.
Crack Resistance of PVD Coatings: Influence of Surface Treatment Prior to Deposition
Authors: Zoestbergen E. , De Hosson J. Th. M.
Published: April 2003

The crack resistance of three different PVD coatings, TiN, Ti(C,N), and a multilayer system of alternating TiN and TiAlN, have been investigated. The three coating systems were deposited onto substrates with a different surface roughness to study the influence of this pretreatment on the crack resistance of the coatings. First, the microstructure and state of stress of the three PVD systems were determined using X-ray diffraction and scanning electron microscopy. Then the coatings are loaded in tension in an ESEM to carry out in situ bending experiments, to assess the crack resistance of the layers. Studying the results of the bending experiments in relation to the characteristic properties of the coatings shows that the compressive residual stresses have a large influence on the moment the first cracks arise. After the initiation of the first crack, the crack resistance of TiN, deposited on the smoothest substrate, is much better than that of TiN/TiAlN and Ti(C,N). Increasing the interface roughness for the Ti(C,N) and the TiN/TiAlN results in an increased crack resistance. For the coatings deposited on the roughest substrates, the crack resistance is, approximately, the same for the three different systems. Spallation of the coatings also has been observed but does not occur frequently.
IL-4 suppresses osteoclast development and mature osteoclast function by a STAT6-dependent mechanism: irreversible inhibition of the differentiation program activated by RANKL
Authors: Moreno Jose L. , Kaczmarek Michele , Keegan Achsah D. , Tondravi Mehrdad
Published: April 2003

Numerous reports have described the effects of interleukin-4 (IL-4) on bone biology. Previous studies, performed using complex coculture systems, demonstrated the effects of IL-4 on osteoblasts and osteoclasts. To directly test the effect of IL-4 on osteoclasts, we took advantage of a simplified system using recombinant receptor activator of nuclear factor κB ligand (RANKL) as the osteoclast differentiation factor. We analyzed the ability of IL-4 to directly regulate osteoclast differentiation and mature osteoclast function. We found that IL-4 inhibited the differentiation of osteoclasts from bone marrow precursors in an irreversible manner and also inhibited the resorptive capacity of mature osteoclasts. In the presence of IL-4, we detected the appearance of tartrate-resistant acid phosphatase (TRAP)–negative multinucleated giant (MNG) cells. Both IL-4 effects were dependent on signal transducer and activator of transcription 6 (STAT6). We found that IL-4 suppresses RANK mRNA expression in the developing precursor cells. When RANK was ectopically expressed under the cytomegalovirus (CMV) promoter in RAW264.7 macrophages, IL-4 treatment did not inhibit osteoclast development. Furthermore, when osteoclastogenesis was induced independently of RANKL by using tumor necrosis factor-α (TNF-α), IL-4 inhibited osteoclast differentiation through a STAT6-dependent mechanism. These results suggest that IL-4 regulates osteoclast development by regulating gene expression, including RANK. We propose that IL-4 irreversibly regulates the lineage commitment of precursor cells by regulating gene expression, resulting in the suppression of osteoclast development and the generation of MNG cells as an alternative pathway of differentiation.
Expression and domain-specific function of GATA-2 during differentiation of the hematopoietic precursor cells in midgestation mouse embryos
Authors: Minegishi Naoko , Suzuki Norio , Yokomizo Tomomasa , Pan Xiaoqing , Fujimoto Tetsuhiro , Takahashi Satoru , Hara Takahiko , Miyajima Atsushi , Nishikawa Shin-ichi , Yamamoto Masayuki
Published: April 2003

The aorta-gonads-mesonephros (AGM) region of the mouse embryo has been assigned as the origin of definitive hematopoiesis. The transcription factor GATA-2 has specific but unclarified roles in early hematopoiesis. To elucidate the expression profile of GATA-2, we prepared transgenic mouse lines containing the green fluorescent protein (GFP) gene driven by GATA-2 gene regulatory elements. We also prepared a mouse line in which GFP reporter sequences were inserted into the endogenous GATA-2 gene. Both mouse mutants expressed GFP in the early hematopoietic tissues. The CD45 antigen, a marker of hematopoietic cells, was expressed in a small fraction of transgene (TG)–derived GFP+ cells. The remaining TG-GFP+/CD45- cells were adherent to plastic and produced CD45+ hematopoietic cells abundantly when cultured in vitro. Exogenous expression of GATA-2 in TG-GFP+/CD45- cells from the AGM region inhibited their differentiation into CD45+ cells. Loss of GATA-2 function through the disruption of the GATA-2 locus enhanced the earlier emergence of CD45+ cells in the yolk sac of the 9.5-day conceptus. These results demonstrated that GATA-2 is expressed in the precursor of hematopoietic cells and works as a gatekeeper to preserve their immaturity. A reduction of GATA-2 expression or activity is required for the differentiation of precursors to hematopoietic cells.
Trauma and acute lung injury
Authors: Tomlinson L , Bellingan GJ
Published: April 2003

Acute lung injury is a serious complication of major trauma occurring as a direct consequence of trauma to the lung or, more commonly, arising indirectly as a consequence of trauma elsewhere to the body. A spectrum of severity exists with acute respiratory distress syndrome (ARDS) defined as the most severe form of injury. The frequency of ARDS with severe trauma is unclear but is believed to occur in approximately 15- 25% of cases, although this is confused by the effects of multiple transfusions and associated injuries including burns and head injury. ARDS from all causes is estimated to occur with a frequency of two to 10 cases per 100 000 population. It causes a huge social and financial impact, with many survivors requiring a prolonged critical care stay and a significant number having a persisting poor quality of life a year after the injury. The mortality is, however, decreasing and stands at approximately 40%. A number of approaches are now recognized that can improve oxygenation and large trials have identified best critical care practice, leading to a reduction in ventilator-induced injury, with associated improvements in outcome.
Clinical examination of the knee following trauma: an evidence-based perspective
Authors: Davis Edward
Published: April 2003

The knee is a common site of injury. The increasing number of clinical tests and greater understanding of the joints biomechanics, lead to difficulties in both the interpretation of the clinical examination and in the reliance that should be placed on specific signs or tests. This article helps review the present evidence surrounding examination of the knee. This will enable clarification of which tests are most appropriate to be applied for specific injuries, and how they should be interpreted by the clinician. The most accurate test currently is that for anterior cruciate ligament deficiency as described by Lachman. Other classically taught tests, such as that of McMurray for meniscal tears, have been demonstrated to be of poor sensitivity and specificity.
Fluid therapy in paediatric trauma
Authors: Turner CLS , Young AER
Published: April 2003

Trauma is the most common cause of death in children over one year of age. Hypovolaemic shock is a life-threatening consequence following trauma. Hypovolaemia may be difficult to identify in children, with hypotension being a late and critical sign. Delayed capillary refill time is a useful clinical adjunct to identify hypovolaemic shock in children. This article reviews paediatric and neonatal maintenance and resuscitation fluid requirements. Fluid therapy is addressed in specific trauma circumstances including head injury, burns, and near drowning. Methods of gaining circulatory access and complications of fluid therapy are also discussed.
Definitive surgical trauma skills: a new skills course for specialist registrars and consultants in general surgery in the United Kingdom
Authors: Ryan JM , Roberts P
Published: April 2003

In an era of increasing subspecialization within UK surgical practice, few senior trainees and a diminishing number of consultants feel competent operating outside their chosen specialist eld. General surgery and orthopaedic trainees, however, remain in the front line of trauma management. Subspecialization is, to some degree, affecting training of orthopaedic surgeons; there are some that do not deal with trauma. However, it is in the so-called field of general surgery that subspecialization has had the greatest impact. Many trainees are now more familiar with endoscopic techniques than open laparotomy and, even within the open abdomen, few wish to explore organ systems or regions outside their `zone of comfort’. Trauma, especially that inflicted by rearms, does not respect anatomical or speciality boundaries. This raises the question of how best to train surgeons in the future to manage severe multisystem injury.

To manage trauma competently there is a need to master operative skills that cover the whole of the abdominal cavity, including the pelvis and the retroperitoneum. General surgeons should be competent and confident to carry out trauma thoracotomies and able to cope with central and peripheral vascular trauma. Further skills and knowledge are also required: these encompass trauma epidemiology, critical decision making and, not least, a detailed knowledge of surgical anatomy. Knowledge can be most severely tested when dealing with multi-system trauma! There is also a particular need to give military surgeons the competencies required to deal with battlefield trauma, 90% of which is caused by penetrating injury. Military surgeons, by definition, still need to be `generalists’.

The Raven department of education at the Royal College of Surgeons of England, the Royal Defence Medical College (now the Royal Centre for Defence Medicine, Birmingham), and the Uniformed Services University of the Health Sciences, Washington, have developed a Definitive Surgical Trauma Skills (DSTS) course to meet this specific training need. This tripartite venture was developed in association with the Societe International de Chirugie (SIC) and the International Association for the Surgery of Trauma and Surgical Intensive Care (IATSIC).
Phase II Study of Pemetrexed With and Without Folic Acid and Vitamin B12 as Front-Line Therapy in Malignant Pleural Mesothelioma
Authors: Scagliotti Giorgio V. , Shin Dong-M. , Kindler Hedy L. , Vasconcelles Michael J. , Keppler Uwe , Manegold Christian , Burris Howard , Gatzemeier Ulrich , Blatter Johannes , Symanowski James T. , Rusthoven James J.
Published: April 2003

Purpose: This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM).

Patients and Methods: Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m2) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B12 supplementation to improve safety.

Results: A total of 64 patients were enrolled. Nine (14.1%) of the 64 patients had a partial response. The Kaplan-Meier estimate for median overall survival was 10.7 months. Forty-three patients received vitamin supplementation for all courses of therapy, and 21 patients did not. Seven of the nine responders were vitamin supplemented. The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients. Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients (median, six v two cycles, respectively). Grade 3/4 neutropenia (23.4%) and grade 3/4 leukopenia (18.8%) were the most common laboratory toxicities. Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events (grade 3, 6.3%; grade 4, 0.0% each). The incidence of these toxicities was generally lower in the supplemented patients.

Conclusion: Single-agent pemetrexed for MPM resulted in a moderate response rate (14.1%) and median overall survival of 10.7 months. Patients supplemented with folic acid and vitamin B12 tolerated treatment better (less toxicity and more cycles of treatment) and had a 5-month greater median overall survival than nonsupplemented patients. These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation.
Angiotensin II AT1 and AT2 Receptors Contribute to Maintain Basal Adrenomedullary Norepinephrine Synthesis and Tyrosine Hydroxylase Transcription
Authors: Jezova Miroslava , Armando Ines , Bregonzio Claudia , Yu Zu-Xi , Qian Sujuan , Ferrans Victor J. , Imboden Hans , Saavedra Juan M.
Published: April 2003

Angiotensin II (Ang II) AT1 receptors have been proposed to mediate the Ang II-dependent and the stress-stimulated adrenomedullary catecholamine synthesis and release. However, in this tissue, most of the Ang II receptors are of the AT2 type. We asked the question whether AT1 and AT2 receptors regulate basal catecholamine synthesis. Long-term AT1 receptor blockade decreased adrenomedullary AT1 receptor binding, AT2 receptor binding and AT2 receptor protein, rat tyrosine hydroxylase (TH) mRNA, norepinephrine (NE) content, Fos-related antigen 2 (Fra-2) protein, phosphorylated cAMP response element binding protein (pCREB), and ERK2. Long-term AT2 receptor blockade decreased AT2 receptor binding, TH mRNA, NE content and Fra-2 protein, although not affecting AT1 receptor binding or receptor protein, pCREB or ERK2. Angiotensin II colocalized with AT1 and AT2 receptors in ganglion cell bodies. AT2 receptors were clearly localized to many, but not all, chromaffin cells. Our data support the hypothesis of an AT1/AT2 receptor cross-talk in the adrenomedullary ganglion cells, and a role for both receptor types on the selective regulation of basal NE, but not epinephrine formation, and in the regulation of basal TH transcription. Whereas AT1 and AT2 receptors involve the Fos-related antigen Fra-2, AT1 receptor transcriptional effects include pCREB and ERK2, indicating common as well as different regulatory mechanisms for each receptor type.
Distinguishing Features of Leucine and α-Ketoisocaproate Sensing in Pancreatic β-Cells
Authors: Gao Zhiyong , Young Robert A. , Li Guizhu , Najafi Habiba , Buettger Carol , Sukumvanich Siam S. , Wong Ryan K. , Wolf Bryan A. , Matschinsky Franz M.
Published: April 2003

Culturing rat islets in high glucose (HG) increased 1-14C-α-ketoisocaproate (KIC) oxidation compared with culturing them in low glucose. Leucine caused insulin secretion (IS) in low glucose but not in HG rat islets, whereas KIC did so in both. Pretreatment with HG for 40 min abolished leucine stimulation of IS by mouse islets and prevented the cytosolic Ca2+ rise without inhibiting IS and Ca2+ increments caused by KIC. When islets were pretreated without glucose and glutamine, aminooxyacetic acid (AOA) markedly decreased KIC effects. When islets were pretreated without glucose and with glutamine, AOA potentiated leucine effects but attenuated KIC effects. AOA stimulated glutamine oxidation in the presence but not the absence of ±2-amino-2-norbornane-carboxylic acid, a nonmetabolized leucine analog. Pretreatment with HG and glutamine partially reversed AOA inhibition of KIC effects. Glucose increased intracellular ATP and GTP, whereas it decreased ADP and GDP in βHC9 cells. Glutamate dehydrogenase activity of βHC9 cell extracts was increased by leucine and attenuated by GTP, but it was potentiated by ADP. In conclusion, leucine and KIC stimulated β-cells via distinct mechanisms. Glutamate dehydrogenase is the sensor of leucine, whereas transamination plays an important role in KIC stimulation of pancreatic β-cells.
Expression of the Mouse Gonadotropin-Releasing Hormone Receptor Gene in αT3-1 Gonadotrope Cells Is Stimulated by Cyclic 3′,5′-Adenosine Monophosphate and Protein Kinase A, and Is Modulated by Steroidogenic Factor-1 and Nur77
Authors: Sadie Hanél , Styger Gustav , Hapgood Janet
Published: April 2003

Regulation of GnRH receptor (GnRHR) expression levels in the pituitary is a crucial control point in reproduction. The promoter of the mouse GnRHR gene contains nuclear receptor half-sites (NRS) at –244/−236 and −15/−7 relative to the translation start site. Although binding of steroidogenic factor-1 (SF-1) to the –244/−236NRS is implicated in mediating basal and gonadotrope-specific expression, no function or protein-DNA interactions have previously been described for the –15/−7NRS. We report that levels of the endogenous GnRHR mRNA in αT3-1 cells are stimulated by forskolin and 8-bromo-cAMP. We also show that the orphan nuclear receptor Nur77 is expressed in αT3-1 cells, and that both SF-1 and Nur77 bind to the –15/−7NRS and –244/−236NRS in vitro. We show that the activity of the proximal (−579/+1) mouse GnRHR promoter is up-regulated by protein kinase A, via a mechanism that is modulated by SF-1, both positively and negatively, through binding to the –244/−236NRS or the –15/−7NRS, respectively. Nur77 appears to be capable of acting as a negative regulator of this response, via the –15/−7NRS. Furthermore, we show that forskolin up-regulates SF-1 mRNA levels in αT3-1 cells, indicating that the levels of SF-1 play a role in modulating the protein kinase A response.
Triazolopyrimidine (Trapidil), a Platelet-Derived Growth Factor Antagonist, Inhibits Parathyroid Bone Disease in an Animal Model for Chronic Hyperparathyroidism
Authors: Lotinun Sutada , Sibonga Jean D. , Turner Russell T.
Published: April 2003

Parathyroid bone disease in humans is caused by chronic hyperparathyroidism (HPT). Continuous infusion of PTH into rats results in histological changes similar to parathyroid bone disease, including increased bone formation, focal bone resorption, and severe peritrabecular fibrosis, whereas pulsatile PTH increases bone formation without skeletal abnormalities. Using a cDNA microarray with over 5000 genes, we identified an association between increased platelet-derived growth factor-A (PDGF-A) signaling and PTH-induced bone disease in rats. Verification of PDGF-A overexpression was accomplished with a ribonuclease protection assay. Using immunohistochemistry, PDGF-A peptide was localized to mast cells in PTH-treated rats. We also report a novel strategy for prevention of parathyroid bone disease using triazolopyrimidine (trapidil). Trapidil, an inhibitor of PDGF signaling, did not have any effect on indexes of bone turnover in normal rats. However, dramatic reductions in marrow fibrosis and bone resorption, but not bone formation, were observed in PTH-treated rats given trapidil. Also, trapidil antagonized the PTH-induced increases in mRNA levels for PDGF-A. These results suggest that PDGF signaling is important for the detrimental skeletal effects of HPT, and drugs that target the cytokine or its receptor might be useful in reducing or preventing parathyroid bone disease.
17β-Hydroxysteroid Dehydrogenase Type XI Localizes to Human Steroidogenic Cells
Authors: Chai Zhonglin , Brereton Phillip , Suzuki Takashi , Sasano Hironobu , Obeyesekere Varuni , Escher Genevieve , Saffery Richard , Fuller Peter , Enriquez Carla , Krozowski Zygmunt
Published: April 2003

We searched expressed sequence tag databases with conserved domains of the short-chain alcohol dehydrogenase superfamily and identified another isoform of 17β-hydroxysteroid dehydrogenase, 17βHSDXI. This enzyme converts 5α-androstane-3α, 17β-diol to androsterone. The substrate has been implicated in supporting gestation and modulating γ-aminobutyric acid receptor activity. 17βHSDXI is colinear with human retinal short-chain dehydrogenase/reductase retSDR2, a protein with no known biological activity (accession no. AAF06939). Of the proteins with known function, 17βHSDXI is most closely related to the retinol-metabolizing enzyme retSDR1, with which it has 30% identity. There is a polymorphic stretch of 15 adenosines in the 5′ untranslated region of the cDNA sequence and a silent polymorphism at C719T. A 17βHSDXI construct with a stretch of 20 adenosines was found to produce significantly more enzyme activity than constructs containing 15 or less adenosines (43% vs. 26%, P < 0.005). The C719T polymorphism is present in 15% of genomic DNA samples. Northern blot analysis showed high levels of 17βHSDXI expression in the pancreas, kidney, liver, lung, adrenal, ovary, and heart. Immunohistochemical staining for 17βHSDXI is strong in steroidogenic cells such as syncytiotrophoblasts, sebaceous gland, Leydig cells, and granulosa cells of the dominant follicle and corpus luteum. In the adrenal 17βHSDXI, staining colocalized with the distribution of 17α-hydroxylase but was stronger in the mid to outer cortex. 17βHSDXI was also found in the fetus and increased after birth. Liver parenchymal cells and epithelium of the endometrium and small intestine also stained. Regulation studies in mouse Y1 cells showed that cAMP down-regulates 17βHSDXI enzymatic activity (40% vs. 32%, P < 0.05) and reduces gene expression to undetectable levels. All-trans-retinoic acid did not affect 17βHSDXI expression or activity, but addition of the retinoid together with cAMP significantly decreased activity over cAMP alone (32% vs. 23%, P < 0.05). Cloning and sequencing of the 17βHSDXI promoter identified the potential nuclear receptor steroidogenic factor-1 half-site TCCAAGGCCGG, and a cluster of three other potential steroidogenic factor-1 half-sites were found in the distal part of intron 1. Collectively, these results suggest a role for 17βHSDXI in androgen metabolism during steroidogenesis and a possible role in nonsteroidogenic tissues including paracrine modulation of 5α-androstane-3α, 17β-diol levels. 17βHSDXI could act by metabolizing compounds that stimulate steroid synthesis and/or by generating metabolites that inhibit it.
A Role for the Endogenous Opioid β-Endorphin in Energy Homeostasis
Authors: Appleyard Suzanne M. , Hayward Michael , Young Juan I. , Butler Andrew A. , Cone Roger D. , Rubinstein Marcelo , Low Malcolm J.
Published: April 2003

Proopiomelanocortin (POMC) neurons in the hypothalamus are direct targets of the adipostatic hormone leptin and contribute to energy homeostasis by integrating peripheral and central information. The melanocortin and β-endorphin neuropeptides are processed from POMC and putatively coreleased at axon terminals. Melanocortins have been shown by a combination of pharmacological and genetic methods to have inhibitory effects on appetite and body weight. In contrast, pharmacological studies have generally indicated that opioids stimulate food intake. Here we report that male mice engineered to selectively lack β-endorphin, but that retained normal melanocortin signaling, were hyperphagic and obese. Furthermore, β-endorphin mutant and wild-type mice had identical orexigenic responses to exogenous opioids and identical anorectic responses to the nonselective opioid antagonist naloxone, implicating an alternative endogenous opioid tone to β-endorphin that physiologically stimulates feeding. These genetic data indicate that β-endorphin is required for normal regulation of feeding, but, in contrast to earlier reports suggesting opposing actions of β-endorphin and melanocortins on appetite, our results suggest a more complementary interaction between the endogenously released POMC-derived peptides in the regulation of energy homeostasis.
CD40 Ligand Blocks Apoptosis Induced by Tumor Necrosis Factor α, Glucocorticoids, and Etoposide in Osteoblasts and the Osteocyte-Like Cell Line Murine Long Bone Osteocyte-Y4
Authors: Ahuja Seema S. , Zhao Shujie , Bellido Teresita , Plotkin Lilian I. , Jimenez Fabio , Bonewald Lynda F.
Published: April 2003

During characterization of the osteocyte-like murine long bone osteocyte-Y4 (MLO-Y4) cell line, comparison was made with antigen-presenting cells of the immune system known as dendritic cells. It was observed that the MLO-Y4 osteocyte-like cells express CD40 antigen and MHC class I antigen, but they are negative for a series of other dendritic cells markers (DEC-205, CD11b, CD11c, CD86, and MHC class II) and immune cell markers [CD45, CD3, CD4, B220, Gr-1, and CD40 ligand (CD40L)]. RT-PCR results showed expression of CD40 mRNA and lack of CD40L mRNA expression. Like MLO-Y4 osteocyte cells, both primary osteoblasts and the osteoblast-like cell lines MC3T3, OCT-1, and 2T3 were shown to express CD40 antigen by fluorescence-activated cell sorting. Because CD40L has been shown to function as an antiapoptotic factor in dendritic cells, it was reasoned that this molecule may have a similar function in bone cells. In three different assays for apoptosis, including trypan blue exclusion, changes in nuclear morphology, and fluorescence-activated cell sorting staining for annexin V/propidium iodide, CD40L significantly inhibited apoptosis of MLO-Y4 cells induced by dexamethasone, TNFα, or etoposide. CD40L also inhibited dexamethasone and TNFα-induced apoptosis in the osteoblast cell lines, OCT1 and MC3T3-E1. These data support the hypothesis that CD40L preserves viability of osteoblasts and osteocytes against a wide variety of apoptotic factors independent of signaling or transcriptional mechanisms. Because osteocyte cell death appears to result in bone loss, these studies have important implications for the treatment of bone loss due to glucocorticoid excess and/or to osteoporosis in general.
Prolactin Suppresses Glucocorticoid-Induced Thymocyte Apoptosis in Vivo
Authors: Krishnan Nithya , Thellin Olivier , Buckley Donna J. , Horseman Nelson D. , Buckley Arthur R.
Published: April 2003

The hypothesis that prolactin (PRL) functions as an immunomodulator was based on studies showing lymphocyte PRL receptors, and its effects on growth, differentiation, and apoptosis in lymphoid cells. However, studies of PRL (PRL−/−) and PRL receptor knockout mice indicated that PRL was not required for immune system development or function under basal conditions. Because PRL maintains survival in glucocorticoid (GC)-treated Nb2-T lymphocytes in vitro, and PRL and GCs are elevated during stress, we investigated whether PRL protected T cells in vivo from GC-induced apoptosis. Adrenalectomized mice [PRL −/−, undetectable PRL; pituitary grafted PRL−/− (PRL−/−Graft), elevated PRL; and PRL+/−, normal PRL] were treated with dexamethasone (DEX) or PBS. Thymocytes and splenocytes were isolated and annexin V labeling of phosphatidylserine, DNA fragmentation, and caspase-3 activation were assessed as indices of apoptosis. Total thymocytes and CD4+ and CD8+ T cells obtained from DEX-treated PRL−/− mice exhibited significantly increased annexin V binding. In contrast, binding was not altered by DEX in PRL−/−Graft thymocytes. In addition, DEX induced classic DNA fragmentation in PRL−/− thymocytes. Elevated serum PRL reduced this effect. Thymocytes from DEX-treated PRL−/− mice exhibited increased caspase-3 activation, which was inhibited in cells from PRL−/−Graft mice. Finally, elevated expression of X-linked inhibitor of apoptosis, XIAP, was observed in thymi from DEX-treated PRL −/−Graft mice. This is the first demonstration that elevated PRL antagonizes apoptosis in thymocytes exposed to GCs in vivo. These observations suggest that, under conditions of increased GCs, such as during stress, elevated PRL functions physiologically to maintain survival and function of T-lymphocytes.
Monitoring system design for estimating the lateral tyre force
Authors: Huh K , Kim J , Yi K
Published: April 2003

Longitudinal and lateral forces acting on tyres are known to be closely related to tractive ability, braking characteristics, handling stability and manoeuvrability of ground vehicles. However, it is not feasible in the operating vehicles to measure the tyre forces directly because of the high cost of sensors, the limitations in sensor technology, interference with tyre rotation and the harsh environment. Another approach is the indirect monitoring technique that can estimate the tyre forces based on remote sensor outputs and vehicle dynamics models. In this paper, in order to develop tyre force-monitoring systems, a monitoring model is proposed utilizing not only the yawing motion but also the roll motion. Based on the monitoring model, a monitoring system is designed to estimate the lateral tyre force acting on each tyre. The monitoring system is constructed on the basis of a new scaled Kalman filter with model error compensator (SKFMEC) technique that is developed in this study to improve the robustness performance of Kalman filter methods. The SKFMEC technique adopts both the well-conditioned observer and the model error compensator concepts. Tyre force estimation performance of the monitoring system is evaluated in the MATLAB simulations where true tyre force data are generated from a 14-degree-of-freedom vehicle model with the combined-slip ‘magic formula’ tyre model.
Achievable roll stability of heavy road vehicles
Authors: Sampson D J M , Cebon D
Published: April 2003

A general purpose numerical model, suitable for simulating the yaw—roll behaviour of torsionally flexible heavy goods vehicles with an arbitrary arrangement of vehicle units, is presented. A controllability analysis is then performed to examine the fundamental limitations in achievable roll stability of heavy vehicles with active roll control systems. It is established that it is not possible to control simultaneously and independently all axle load transfers and body roll angles. The best achievable control objective for maximizing roll stability is shown to be setting the normalized load transfers at all critical axles to be equal, while taking the largest inward suspension roll angle to the maximum allowable angle. The results of a simulation of a tractor—semitrailer vehicle with a full—state feedback active roll control system are presented. It is shown that the roll stability of the vehicle can be increased by 30-40 per cent for steady state and transient manoeuvres and that the handling performance improves significantly.
A study of shift control using the clutch pressure pattern in automatic transmission
Authors: Han Woosung , Yi Seung-Jong
Published: April 2003

It is necessary to understand the overall system including engine, torque converter, multiplate clutch, band brake, one-way clutch, planetary gears, road load and tyre to analyse the performance of the vehicle powertrain. The performance of the powertrain can be analysed using dynamic models including transient characteristics and the equations of motion are derived from the dynamic models of the powertrain. In this study, the shift transient characteristics of the vehicle equipped with a Ravigneaux-type planetary gears automatic transmission has been investigated. A shift control using engine torque reduction and optimum pressure trajectory has also been investigated in order to enhance transient characteristics during shift.
Determination of plume impingement disturbance characteristics for the ROCSAT-1 satellite
Authors: Yang A-S , Kuo T-C
Published: April 2003

The impingement disturbance characteristics of the hydrazine thruster plumes have been examined comprehensively for the ROCSAT-1 satellite. In this study, the velocity and temperature distributions at the nozzle exit are obtained from the nozzle flowfield analysis. The axial velocity, transverse velocity and temperature profiles are further correlated with the curve-fitting procedure for resolving inflow properties of molecules ejected into a vacuum. The free-molecular direct simulation Monte Carlo technique is used to describe the particle nature of the distant plume flow behaviour near the impingement surface. The inflow molecular motions as well as the collision interactions between the molecules and the solid surface are treated on a probabilistic basis. On the other hand, the inter-collisions among molecules are considered to be relatively unimportant in the far-field plume region. A reasonable number of simulated molecules is also employed to reproduce the fluid behaviour in the macroscopic level. The predicted disturbance torques and thrust loss are found to be much less than the design control torques and the nominal thrust force for ROCSAT-1 satellite, indicating that the plume impingement effect will not cause any performance deterioration of the propulsive function.
Flight deck indication of health monitoring data—a critique
Authors: Evans A
Published: April 2003

In September 1995 there was an incident involving an AS332L Super Puma helicopter over the North Sea. This followed the onset of high vibration due to the fatigue failure of a tail rotor blade retaining hinge. This was the first major vibration incident involving a helicopter fitted with a health and usage monitoring system (HUMS). The UK Air Accidents Investigation Branch made a number of recommendations. One was that the UK Civil Aviation Authority (CAA) should develop the concept of providing a flight deck display of health monitoring information to the flight crew. The CAA asked the Helicopter Health Monitoring Advisory G roup (HHM AG) (an industry body that advises the CAA) to consider the issue. This paper will examine the findings of the H HMAG working group and discuss the practicality of such systems in an operational environment.
Simplified modellization of gear micropitting
Authors: Antoine F , Besson J-M
Published: April 2003

This document gives a simplified method of calculating gear micropitting. The method has been developed by EUROCOPTER. The objective was to provide a model that took into consideration the maximum number of parameters in order to model the different physical phenomena, particularly:

an oil-film thickness calculation taking the influence of pressure into consideration a simplified modellization of roughness an estimation of the plastification effect on the roughness overpressure at the contact surface taking into account the combined effects of roughness and oil-film thickness.

The elaborated model is presented in an Excel file form. The application program is called APICS (approche du pitting par calculs simplifiés). In order to validate this model, this program has been applied to:

An epicyclic gear train of a helicopter. Tests on discs as part of the ASETT European program. Discs are in hardened M50NiL Duplex (surface treatment: carburized and nitrided). Different kinds of surface finishing were proposed. The reference case of discs in 16NCD13 without thermochemical treatment has been also treated. FZG gear benchtests, also as part of the ASETT program. Gears have been manufactured in hardened M50NiL Duplex, with different kinds of surface finishing proposed.

The results of the calculations express quite exactly the experimental facts observed on discs and gears for a wide range of studied cases, covering different materials, different kinds of case hardening and different kinds of surface finishing.
Innovative actuators for active flow and noise control
Authors: Raman G , Cain A B
Published: April 2003

Active flow control (AFC) has the potential to improve the efficiency of systems that involve both internal and external fluid flow. The primary driver in AFC is the expectation that the control will result in significant performance benefits at the system level with all trade-offs factored in. Successful application to aircraft systems can produce lighter, stealthier, agile aircraft with increased range, payload and a muffled acoustic signature. The design of an AFC system requires knowledge of flow phenomena and the selection of appropriate actuators, sensors and a control algorithm. The present overview focuses on actuators. Examples of flow and noise control presented here are restricted to open-loop systems. Various aspects of actuator utilization include actuator output characterization, exploiting resonances (plenum, structural or aeroacoustic) to enhance actuator amplitude and the different modes of actuation. A brief description of a high-bandwidth actuator is also provided, followed by a variety of application examples including edgetone suppression, cavity noise suppression, impingement noise suppression and jet mixing enhancement. The review concludes with a description of the successful application of AFC to the exhaust plume from an aircraft engine (JT8D).
The impact of cage ventilation on rats housed in IVC systems
Authors: Krohn Thomas C. , Hansen Axel Kornerup , Dragsted Nils
Published: April 2003

Today the use of individually ventilated cage systems (IVC systems) is common, especially for housing transgenic rodents. Typically, in each cage a ventilation rate of 40 to 50 air changes per hour is applied, but in some systems even up to 120 air changes per hour is applied. To reach this rate, the air is blown into the cage at a relatively high speed. However, at the animal's level most systems ventilate with an air speed of approximately 0.2 m/s. In the present paper, two studies were conducted, one analysing whether an air speed below 0.2 m/s or just above 0.5 m/s affects the rats, and another study analysing whether air changes of 50, 80 and 120 times per hour affect the rats. In both studies, monitoring of preferences as well as physiological parameters such as heart rate and blood pressure, was used to show the ability of the animals to register the different parameters and to avoid them if possible. Air speeds inside the cage of as high as 0.5 m/s could not be shown to affect the rats, while the number of air changes in each cage should be kept below 80 times per hour to avoid impacts on physiology (heart rate and systolic blood pressure). Also the rats prefer cages with air changes below 80 times per hour if they have the opportunity of choosing, as shown in the preference test.